Safety and Efficacy Study of Exenatide Once Weekly in Adolescents with Type 2 Diabetes

Study identifier:D5551C00002

ClinicalTrials.gov identifier:NCT01554618

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 3, Double-Blind, Placebo-Controlled, Randomized, Multi-Center Study to Assess the Safety and Efficacy of Exenatide Once Weekly in Adolescents with Type 2 Diabetes

Medical condition

children and adolescent with type 2 diabetes

Phase

Phase 3

Healthy volunteers

Study drug

Exenatide Once Weekly, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

10 Years - 17 Years

Date

Study Start Date: 02 Dec 2011

Primary Completion Date: 06 May 2020

Study Completion Date: 05 May 2021

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2021 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

This Phase 3, double-blind (controlled assessment period), randomized, multicenter, placebo-controlled parallel study is designed to examine the efficacy and safety of EQW compared to placebo (PBO) in adolescents with type 2 diabetes for 24 weeks. This study will assess safety and efficacy of EQW (as monotherapy and adjunctive therapy to oral antidiabetic agents and/or insulin). At least 40% and not more than 60% of the randomized patients must be females. At least 40% of patients should be recruited from areas with similar ethnicity and lifestyle to those of the European Union member states. Long term safety and efficacy of EQW will subsequently be monitored for 28 weeks in the open-label, uncontrolled extension period (through Week 52). The study will be terminated at Visit 11 (Week 62/Study Termination) which will be a follow-up visit occurring 10 weeks after the last dose administration at Visit 10 (Week 52). This study will be conducted in 77 patients with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. During the controlled assessment period, approximately 77 patients will be randomly assigned in a 5:2 ratio to either EQW 2 mg (Group A) or PBO (Group B), to yield at least 70 evaluable patients: at least 50 patients in the exenatide and at least 20 patients in the PBO group. Following the 24-week controlled assessment period, patients assigned to the EQW 2 mg treatment (Group A) will continue to be treated with EQW 2 mg during the extension period (through Week 52). Patients randomized to PBO (Group B) will receive EQW 2 mg beginning at the start of the extension period, Week 25 through Week 52. In addition to receiving study medications, all patients will participate in a lifestyle intervention program encompassing diet and physical activity modifications following the signing of the informed consent and assent forms (Visit 1 [Week -2]) through the end of the extension period (Week 52). Following Visit 11 (Week 62/Study Termination), patients whose height increase is at least 5 mm between Visit 8 (Week 28) and Visit 11 (Week 62/Study Termination) will participate in a long-term safety follow-up period. Patients who discontinue study medication prior to Visit 11 (Week 62/Study Termination) will also participate in the Extended Safety Follow-up Period, unless they have a height increase of less than 5 mm over a 6-month interval at study site visits prior to discontinuation of study medication. Patients who do not have height assessments at study-site visits over a 6-month interval prior to discontinuation of study medication will enter the Extended Safety Follow-up Period. The Extended Safety Follow Up Period will continue for up to 3 years or until the difference between two 6-month interval visits is less than a 5 mm increase (whichever comes first). No study medication will be administered during the Extended Safety Follow-up Period. Blood samples will be collected for calcitonin and carcinoembryonic antigen (CEA) laboratory measurements.

Location

Research Site

Haifa, Israel, 31096

Location

Research Site

Beer Sheva, Israel, 84101

Location

Research Site

Ramat Gan, Israel, 5265601

Location

Research Site

Veracruz, Mexico, 91910

Location

Research Site

Guadalajara, Mexico, 44130

Location

Research Site

Kuwait City, Kuwait, 1180

Location

Research Site

Pleven, Bulgaria, 5800

Location

Research Site

Sevlievo, Bulgaria, 5400

Arms	Assigned Interventions
Experimental: EQW Exenatide once weekly	Drug: Exenatide Once Weekly 2 mg exenatide once weekly Other Name: BYDUREON
Placebo Comparator: Placebo Placebo once weekly	Drug: Placebo Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted in adolescents (aged 10 to 17 years inclusive) with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. 27 study centers in 6 countries randomized patients during the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study had a screening period (5 weeks), controlled assessment period (24 weeks; patients randomized 5:2 to exenatide or placebo), open-label extension period (28 weeks) and post-treatment follow-up period (10 weeks). 84 patients were randomized but 1 due to clinical error and immediately discontinued, thus, 83 patients were included in the study.

Reporting Groups

	Description
Exenatide	Controlled assessment Period: Patients received exenatide 2 milligrams (mg) subcutaneous (SC) injection once weekly for 24 weeks. Extension period: Patients continued to receive exenatide 2 mg SC once weekly during the open-label extension period for 28 weeks (through Week 52).
Placebo	Controlled assessment period: Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks. Extension period: Patients then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Participant Flow for 3 periods

Period 1: Randomized Through Start of Treatment

	Exenatide	Placebo
STARTED	59	24
COMPLETED	58	24
NOT COMPLETED	1	0
Adverse Event	1	0

Period 2: Controlled Assessment Period

	Exenatide	Placebo
STARTED	58	24
COMPLETED	50	23
NOT COMPLETED	8	1
Lost to Follow-up	2	1
Withdrawal by Subject	6	0

Period 3: Open-Label Extension Period

	Exenatide	Placebo
STARTED	49^[1]	23
COMPLETED	46	18
NOT COMPLETED	3	5
Withdrawal by Subject	2	3
Physician Decision	0	1
Lost to Follow-up	1	1

[1]	1 patient who was noncompliant with study medication did not enter the open-label extension period

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Baseline analysis performed on Intent-to-Treat (ITT) Analysis Set which consisted of all randomized patients who received at least 1 dose of randomized study medication.

Reporting Groups

	Description
Exenatide	Controlled assessment period: Patients received exenatide 2 mg SC injection once weekly for 24 weeks. Extension period: Patients continued to receive exenatide 2 mg SC once weekly during the open-label extension period for 28 weeks (through Week 52).
Placebo	Controlled assessment period: Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks. Extension period: Patients then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Baseline Measures

	Exenatide	Placebo	Total
Number of Participants [units: Participants]	58	24	82
Age Continuous [units: years] Mean ± Standard Deviation	14.9 ± 1.88	15.6 ± 1.66	15.1 ± 1.84
Sex: Female, Male [units: participants]
Female	31	17	48
Male	27	7	34
Age, Customized ^[1] [units: participants]
< 10	0	0	0
≥ 10 to ≤ 12	8	3	11
≥ 13 to ≤ 16	36	12	48
> 16	14	9	23
Race/Ethnicity, Customized [units: participants]
White	23	12	35
Black or African American	17	8	25
Asian	2	1	3
Native Hawaiian or Other Pacific Islander	0	0	0
American Indian or Alaska Native	4	1	5
Other	12	2	14
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	25	8	33
Not Hispanic or Latino	29	13	42
Unknown or Not Reported	4	3	7
Region of Enrollment [units: participants]
Bulgaria	1	0	1
Hungary	3	1	4
Israel	4	3	7
Mexico	13	2	15
United States	35	17	52
Kuwait	2	1	3

Outcome Measures

1. Primary Outcome Measure: Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Primary
Measure Name	Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) [units: percentage (% HbA1c)] Least Squares Mean (Standard Error)	-0.36 (0.184)	0.49 (0.273)

Statistical Analysis 1 for Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.012
Other^[5]	-0.85
Standard Error of the mean	± 0.330
95% Confidence Interval	( -1.51 to -0.19 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline HbA1c value (continuous) and baseline HbA1c by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

2. Primary Outcome Measure: Percentage of Patients with On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) [ Time Frame: Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up ]

Measure Type	Primary
Measure Name	Percentage of Patients with On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)
Measure Description	A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs [SAEs] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.
Time Frame	Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. One patient who was randomized to placebo received a dose of exenatide in error and was subsequently reassigned to the exenatide treatment group for analyses based on actual treatment.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	59	23
Percentage of Patients with On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) [units: percentage of participants]
Any AE	61.0	73.9
Any AE with outcome of death	0	0
Any SAE	3.4	4.3
Any AE leading to discontinuation of treatment	0	0
Any AE leading to discontinuation from study	0	0
Any AE related to treatment	25.4	21.7

No statistical analysis provided for Percentage of Patients with On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)

3. Primary Outcome Measure: Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 [ Time Frame: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24 ]

Measure Type	Primary
Measure Name	Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24
Measure Description	Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers < 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.
Time Frame	Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients receiving exenatide in the controlled assessment period were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).

Measured Values

	Treatment Period – Exenatide
Number of Participants Analyzed [units:participants]	59
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 [units: percentage of participants]
Week 4: High Positive	17.0
Week 4: Low Positive	30.2
Week 4: Treatment-Emergent ADA Positive	45.3
Week 8: High Positive	53.8
Week 8: Low Positive	38.5
Week 8: Treatment-Emergent ADA Positive	92.3
Week 12: High Positive	60.0
Week 12: Low Positive	38.0
Week 12: Treatment-Emergent ADA Positive	98.0
Week 24: High Positive	40.8
Week 24: Low Positive	55.1
Week 24: Treatment-Emergent ADA Positive	95.9

No statistical analysis provided for Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24

4. Secondary Outcome Measure: Change from Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Change from Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) [units: milligrams per deciliter (mg/dL)] Least Squares Mean (Standard Error)	-5.2 (7.65)	16.5 (11.32)

Statistical Analysis 1 for Change from Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.119
Other^[5]	-21.6
Standard Error of the mean	± 13.70
95% Confidence Interval	( -49.0 to 5.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline fasting plasma glucose value, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline fasting plasma glucose by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

5. Secondary Outcome Measure: Change from Baseline in Body Weight to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Body Weight to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Change from Baseline in Body Weight to Week 24 (Controlled Assessment Period) [units: kilogram (kg)] Least Squares Mean (Standard Error)	-0.59 (0.665)	0.63 (0.982)

Statistical Analysis 1 for Change from Baseline in Body Weight to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.307
Other^[5]	-1.22
Standard Error of the mean	± 1.189
95% Confidence Interval	( -3.59 to 1.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline body weight, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline body weight by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

6. Secondary Outcome Measure: Change from Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Change from Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) [units: picomoles per liter (pmol/L)] Least Squares Mean (Standard Error)	79.6 (52.28)	-15.3 (78.49)

Statistical Analysis 1 for Change from Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.323
Other^[5]	94.9
Standard Error of the mean	± 95.26
95% Confidence Interval	( -95.6 to 285.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline fasting insulin, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline fasting insulin by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

7. Secondary Outcome Measure: Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) [ Time Frame: At Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)
Measure Description	The percentage of patients achieving HbA1c goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	At Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients with data available were included in the analysis.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	48	22
Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) [units: percentage of participants] Number (95% Confidence Interval)
HbA1c <6 .5%	19.0 (8.9 to 29.1)	4.2 (0.0 to 12.2)
HbA1c ≤ 6.5%	19.0 (8.9 to 29.1)	4.2 (0.0 to 12.2)
HbA1c < 7.0%	31.0 (19.1 to 42.9)	8.3 (0.0 to 19.4)

Statistical Analysis 1 for Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.077
Other^[5]	14.8
95% Confidence Interval	( 1.9 to 27.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in HbA1c < 6.5%: Treatment group comparison was based on CMH test stratified by screening HbA1c (<9.0% or >=9.0%). P-value was from the general association statistic.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo. Difference was the risk difference of the 2 proportions.

Statistical Analysis 2 for Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.077
Other^[5]	14.8
95% Confidence Interval	( 1.9 to 27.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in HbA1c ≤ 6.5%: Treatment group comparison was based on CMH test stratified by screening HbA1c (<9.0% or >=9.0%). P-value was from the general association statistic.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo. Difference was the risk difference of the 2 proportions.

Statistical Analysis 3 for Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.020
Other^[5]	22.7
95% Confidence Interval	( 6.5 to 39.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in HbA1c < 7.0%: Treatment group comparison was based on CMH test stratified by screening HbA1c (<9.0% or >=9.0%). P-value was from the general association statistic.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo. Difference was the risk difference of the 2 proportions.

8. Secondary Outcome Measure: Change from Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International [SI] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with data available were included in the analysis.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Change from Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) [units: millimoles per liter (mmol/L)] Mean (Standard Deviation)
Total Cholesterol	-0.117 (0.7124)	-0.114 (0.5819)
HDL-C	-0.035 (0.1950)	-0.047 (0.1039)
LDL-C	-0.050 (0.5618)	-0.110 (0.5983)
Triglycerides	-0.122 (1.0303)	0.094 (0.6626)

No statistical analysis provided for Change from Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)

9. Secondary Outcome Measure: Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) [units: millimeters mercury (mmHg)] Least Squares Mean (Standard Error)
SBP	-0.7 (1.48)	2.2 (2.15)
DBP	0.2 (1.00)	-1.3 (1.45)

Statistical Analysis 1 for Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.284
Other^[5]	-2.8
Standard Error of the mean	± 2.61
95% Confidence Interval	( -8.0 to 2.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in SBP: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline SBP, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline SBP by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

Statistical Analysis 2 for Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.376
Other^[5]	1.6
Standard Error of the mean	± 1.77
95% Confidence Interval	( -2.0 to 5.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in DBP: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline DBP, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline DBP by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

10. Secondary Outcome Measure: Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) [ Time Frame: At Week 4, Week 8, Week 12, Week 18 and Week 24 ]

Measure Type	Secondary
Measure Name	Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period)
Measure Description	Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value > 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time Frame	At Week 4, Week 8, Week 12, Week 18 and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with data available at each specified visit were included in the analysis.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	58	24
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) [units: participants]
Week 4	0	0
Week 8	0	0
Week 12	0	0
Week 18	1	0
Week 24	0	0

No statistical analysis provided for Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period)

11. Secondary Outcome Measure: Change from Baseline in Homeostasis Model Assessments – Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) [ Time Frame: Baseline (Week 0) and Week 24 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Homeostasis Model Assessments – Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period)
Measure Description	Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Homeostasis model assessments were only performed in patients who were not taking insulin.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	14	7
Change from Baseline in Homeostasis Model Assessments – Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) [units: percentage (%HOMA-B and %HOMA-S)] Least Squares Mean (Standard Error)
HOMA-B	63.98 (39.552)	-26.39 (56.138)
HOMA-S	0.62 (3.607)	7.37 (4.914)

Statistical Analysis 1 for Change from Baseline in Homeostasis Model Assessments – Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.211
Other^[5]	90.37
Standard Error of the mean	± 69.207
95% Confidence Interval	( -57.27 to 238.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in HOMA-B: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline HOMA-B, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline HOMA-B by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

Statistical Analysis 2 for Change from Baseline in Homeostasis Model Assessments – Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period)

Groups^[1]	Controlled Assessment Period – Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.289
Other^[5]	-6.75
Standard Error of the mean	± 6.173
95% Confidence Interval	( -19.80 to 6.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment difference in HOMA-S: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline HOMA-S, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline HOMA-S by visit interaction as fixed effects, using an unstructured covariance matrix.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Exenatide versus Placebo

12. Secondary Outcome Measure: Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) [ Time Frame: At Week 4, Week 8, Week 12, Week 18 and Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period)
Measure Description	Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the “Injection site reactions” higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time Frame	At Week 4, Week 8, Week 12, Week 18 and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients with data available at each specified visit were included in the analysis.

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.

Measured Values

	Controlled Assessment Period – Exenatide	Controlled Assessment Period – Placebo
Number of Participants Analyzed [units:participants]	59	23
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) [units: percentage of participants]
Week 4	8.5	8.7
Week 8	3.5	4.3
Week 12	1.9	0
Week 18	0	0
Week 24	0	0

No statistical analysis provided for Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period)

13. Secondary Outcome Measure: Change from Baseline in HbA1c to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in HbA1c to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	39	17
Change from Baseline in HbA1c to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: percentage (% HbA1c)] Mean (Standard Deviation)	-0.10 (1.711)	0.53 (2.123)

No statistical analysis provided for Change from Baseline in HbA1c to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

14. Secondary Outcome Measure: Change from Baseline in FPG Concentration to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in FPG Concentration to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	38	16
Change from Baseline in FPG Concentration to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: mg/dL] Mean (Standard Deviation)	-1.8 (62.64)	10.6 (75.49)

No statistical analysis provided for Change from Baseline in FPG Concentration to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

15. Secondary Outcome Measure: Change from Baseline in Body Weight to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Body Weight to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	39	18
Change from Baseline in Body Weight to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: kg] Mean (Standard Deviation)	0.04 (6.088)	-0.04 (4.687)

No statistical analysis provided for Change from Baseline in Body Weight to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

16. Secondary Outcome Measure: Change from Baseline in Fasting Insulin to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Fasting Insulin to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	37	16
Change from Baseline in Fasting Insulin to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: pmol/L] Mean (Standard Deviation)	-32.4 (273.57)	121.5 (379.13)

No statistical analysis provided for Change from Baseline in Fasting Insulin to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

17. Secondary Outcome Measure: Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: At Week 52 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	The percentage of patients achieving HbA1c goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	At Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients who received open-label exenatide and with data available were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	39	17
Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: percentage of participants]
HbA1c < 6.5%	30.8	23.5
HbA1c ≤ 6.5%	30.8	23.5
HbA1c < 7.0%	35.9	29.4

No statistical analysis provided for Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

18. Secondary Outcome Measure: Change from Baseline in Lipids Profiles to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Lipids Profiles to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	37	15
Change from Baseline in Lipids Profiles to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: mmol/L] Mean (Standard Deviation)
Total Cholesterol	-0.188 (0.4199)	-0.255 (0.9075)
HDL-C	0.004 (0.1740)	-0.076 (0.2327)
LDL-C	-0.175 (0.4025)	-0.152 (0.7682)
Triglycerides	-0.155 (1.1108)	-0.043 (0.5971)

No statistical analysis provided for Change from Baseline in Lipids Profiles to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

19. Secondary Outcome Measure: Change from Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	39	18
Change from Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: mmHg] Mean (Standard Deviation)
SBP	-0.7 (13.09)	-0.6 (8.73)
DBP	1.1 (8.65)	-2.5 (10.65)

No statistical analysis provided for Change from Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

20. Secondary Outcome Measure: Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52 ]

Measure Type	Secondary
Measure Name	Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value > 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time Frame	At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients who received open-label exenatide and with data available were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	49	23
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: participants]
Week 4	0	0
Week 8	0	0
Week 12	0	0
Week 18	1	0
Week 24	0	0
Week 28	2	1
Week 40	2	0
Week 52	0	0

No statistical analysis provided for Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

21. Secondary Outcome Measure: Change from Baseline in HOMA-B and HOMA-S to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Baseline (Week 0) and Week 52 ]

Measure Type	Secondary
Measure Name	Change from Baseline in HOMA-B and HOMA-S to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	8	5
Change from Baseline in HOMA-B and HOMA-S to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: percentage (%HOMA-B and %HOMA-S)] Mean (Standard Deviation)
HOMA-B	-2.58 (130.435)	42.02 (183.869)
HOMA-S	9.85 (12.366)	2.36 (7.631)

No statistical analysis provided for Change from Baseline in HOMA-B and HOMA-S to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

22. Secondary Outcome Measure: Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52 ]

Measure Type	Secondary
Measure Name	Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the “Injection site reactions” higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time Frame	At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients with data available at each specified visit were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	50	22
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: percentage of participants]
Week 4	10.0	9.1
Week 8	4.0	4.5
Week 12	2.0	0
Week 18	0	0
Week 24	0	0
Week 28	4.0	0
Week 40	0	0
Week 52	0	0

No statistical analysis provided for Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

23. Secondary Outcome Measure: Plasma Exenatide Concentrations to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [ Time Frame: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52 ]

Measure Type	Secondary
Measure Name	Plasma Exenatide Concentrations to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)
Measure Description	Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded.
Time Frame	Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic (PK) Analysis Set consisted of all patients who received at least 1 dose of exenatide, for whom any postdose data were available and who did not deviate from the protocol in ways that would significantly affect the PK analyses. Only patients who received open-label exenatide and with data available were included in the analysis.

Reporting Groups

	Description
Treatment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Treatment Period - Placebo then Exenatide	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).

Measured Values

	Treatment Period – Exenatide	Treatment Period - Placebo then Exenatide
Number of Participants Analyzed [units:participants]	55	19
Plasma Exenatide Concentrations to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period) [units: picograms per milliliter] Geometric Mean (Geometric Coefficient of Variation)
Baseline	NA (NA%)^[1]
Week 4	41.51 (91.9%)
Week 8	130.60 (83.8%)
Week 12	163.58 (92.3%)
Week 24	140.81 (84.0%)	NA (NA%)^[1]
Week 52	88.88 (79.2%)	105.56 (154.9%)

No statistical analysis provided for Plasma Exenatide Concentrations to Week 52 Among Patients who Received Open-Label Exenatide (Treatment Period)

Serious Adverse Events

Time Frame	After the first dose of study medication in period through the end of the treatment in period + 90 days for SAEs (or + 7 days for non-serious (i.e. Other) AEs. Overall time frame: up to maximum of approximately 37 weeks and 41 weeks for controlled assessment period and extension period, respectively.
Additional Description	The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. One patient who was randomized to placebo received a dose of exenatide in error and was subsequently reassigned to the exenatide treatment group for analyses based on actual treatment (ie, for analyses based on the Safety Analysis Set).

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Extension Period - Exenatide	Patients received open-label exenatide 2 mg SC injection once weekly for 28 weeks during the extension period. Patients in this treatment group had previously received exenatide during the controlled assessment period.
Extension Period – Placebo to Exenatide	Patients received open-label exenatide 2 mg SC injection once weekly for 28 weeks during the extension period. Patients in this treatment group had previously received placebo during the controlled assessment period.

Serious Adverse Events

Controlled Assessment Period – Exenatide

Controlled Assessment Period – Placebo

Extension Period - Exenatide

Extension Period – Placebo to Exenatide

Total, serious adverse events

# participants affected / at risk

2/59 (3.39%)

1/23 (4.35%)

3/50 (6.00%)

1/22 (4.55%)

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/59 (0.00%)

0/23 (0.00%)

1/50 (2.00%)

0/22 (0.00%)

# events

Gastrointestinal disorders

Irritable bowel syndrome¹,^†

# participants affected / at risk

0/59 (0.00%)

1/23 (4.35%)

0/50 (0.00%)

0/22 (0.00%)

# events

Infections and infestations

Abscess limb¹,^†

# participants affected / at risk

1/59 (1.69%)

0/23 (0.00%)

0/50 (0.00%)

0/22 (0.00%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/59 (0.00%)

0/23 (0.00%)

1/50 (2.00%)

0/22 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/59 (0.00%)

0/23 (0.00%)

1/50 (2.00%)

0/22 (0.00%)

# events

Psychiatric disorders

Major depression¹,^†

# participants affected / at risk

1/59 (1.69%)

0/23 (0.00%)

0/50 (0.00%)

0/22 (0.00%)

# events

Psychiatric disorders

Suicidal ideation¹,^†

# participants affected / at risk

0/59 (0.00%)

0/23 (0.00%)

1/50 (2.00%)

1/22 (4.55%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 23.0

Other Adverse Events

Time Frame	After the first dose of study medication in period through the end of the treatment in period + 90 days for SAEs (or + 7 days for non-serious (i.e. Other) AEs. Overall time frame: up to maximum of approximately 37 weeks and 41 weeks for controlled assessment period and extension period, respectively.
Additional Description	The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. One patient who was randomized to placebo received a dose of exenatide in error and was subsequently reassigned to the exenatide treatment group for analyses based on actual treatment (ie, for analyses based on the Safety Analysis Set).

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Controlled Assessment Period – Exenatide	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.
Controlled Assessment Period – Placebo	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Extension Period - Exenatide	Patients received open-label exenatide 2 mg SC injection once weekly for 28 weeks during the extension period. Patients in this treatment group had previously received exenatide during the controlled assessment period.
Extension Period – Placebo to Exenatide	Patients received open-label exenatide 2 mg SC injection once weekly for 28 weeks during the extension period. Patients in this treatment group had previously received placebo during the controlled assessment period.

Other Adverse Events

Controlled Assessment Period – Exenatide

Controlled Assessment Period – Placebo

Extension Period - Exenatide

Extension Period – Placebo to Exenatide

Total, other (not including serious) adverse events

# participants affected / at risk

25/59 (42.37%)

10/23 (43.48%)

10/50 (20.00%)

4/22 (18.18%)

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

2/59 (3.39%)

3/23 (13.04%)

1/50 (2.00%)

0/22 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

3/59 (5.08%)

0/23 (0.00%)

1/50 (2.00%)

0/22 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

5/59 (8.47%)

1/23 (4.35%)

1/50 (2.00%)

0/22 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

4/59 (6.78%)

1/23 (4.35%)

0/50 (0.00%)

1/22 (4.55%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/59 (5.08%)

0/23 (0.00%)

2/50 (4.00%)

0/22 (0.00%)

# events

General disorders and administration site conditions

Injection site erythema¹,^†

# participants affected / at risk

3/59 (5.08%)

1/23 (4.35%)

0/50 (0.00%)

0/22 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

4/59 (6.78%)

2/23 (8.70%)

1/50 (2.00%)

1/22 (4.55%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

6/59 (10.17%)

0/23 (0.00%)

2/50 (4.00%)

0/22 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

3/59 (5.08%)

2/23 (8.70%)

0/50 (0.00%)

0/22 (0.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

1/59 (1.69%)

1/23 (4.35%)

0/50 (0.00%)

2/22 (9.09%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

3/59 (5.08%)

0/23 (0.00%)

1/50 (2.00%)

0/22 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

3/59 (5.08%)

0/23 (0.00%)

0/50 (0.00%)

0/22 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

4/59 (6.78%)

2/23 (8.70%)

2/50 (4.00%)

1/22 (4.55%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

4/59 (6.78%)

1/23 (4.35%)

0/50 (0.00%)

2/22 (9.09%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 23.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data

For statistical analyses of change from baseline in HOMA-B and HOMA-S, due to the limited sample size (n=14 and n=7 in the extenatide and placebo groups, respectively) it is difficult to accurately interpret these data. The study design included an extended safety follow-up period which continued for up to 3 years or until the increase in height between two 6-month interval visits was <5 mm (whichever came first). No study medication was administered during the extended safety follow-up period.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

redacted SAP
Download
redacted CSP
Download
CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

redacted SAP

redacted CSP

CSR Synopsis

Trial Results Summaries