A Study to Assess the Effect of Exenatide Treatment on Mean 24-Hour Heart Rate in Patients with Type 2 Diabetes

Study identifier:H8O-MC-GWCD

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Study to Assess the Effect of Exenatide Treatment on Mean 24-Hour Heart Rate in Patients with Type 2 Diabetes

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 3

Healthy volunteers

Study drug

exenatide, placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 01 Sept 2007

Primary Completion Date: 01 Apr 2008

Study Completion Date: 01 Apr 2008

Study design

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

Verification:

Verified 01 Mar 2015 by AstraZeneca Pharmaceuticals

Collaborators

Eli Lilly and Company

Inclusion and exclusion criteria

Location

Research Site

Toronto, Ontario, Canada

Location

Research Site

Halifax, Nova Scotia, Canada

Location

Research Site

Etten-Leur, Netherlands

Location

Research Site

Utrecht, Netherlands

Location

Research Site

Rotterdam, Netherlands

Location

Research Site

Leiden, Netherlands

Arms	Assigned Interventions
Experimental: Exenatide Arm This arm will receive 5mcg exenatide for 4 weeks, and then 10mcg exenatide for the remaining 8 weeks of the study.	Drug: exenatide subcutaneous injection, 5mcg or 10mcg, twice a day Other Name: Byetta Other Name: AC2993 Other Name: LY2148568
Placebo Comparator: Placebo Arm This arm will receive placebo injection (volume equivalent to the exenatide injection in the experimental arm).	Drug: placebo subcutaneous injection, volume equivalent to active, twice a day

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Participant Flow: Overall Study

	Exenatide BID	Placebo
STARTED	28	26
COMPLETED	22	23
NOT COMPLETED	6	3
Adverse Event	0	1
Subject Decision	4	2
Loss of Glucose Control	2	0

Baseline Characteristics

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

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Baseline Measures

	Exenatide BID	Placebo	Total
Number of Participants [units: Participants]	28	26	54.0
Age Categorical [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	23	23	46
>=65 years	5	3	8
Age Continuous [units: years] Mean ± Standard Deviation	56.62 ± 10.90	54.14 ± 10.13	55.43 ± 10.51
Gender, Male/Female [units: participants]
Female	9	15	24
Male	19	11	30

Outcome Measures

1. Primary Outcome Measure: Change in mean 24-hour heart rate from baseline to endpoint [ Time Frame: 12 weeks ]

Measure Type	Primary
Measure Name	Change in mean 24-hour heart rate from baseline to endpoint
Measure Description	Change from baseline to endpoint in average heart rate measured over 24 hours by an ambulatory blood pressure monitor.
Time Frame	12 weeks
Safety Issue?	No

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.
Intent to treat; Last observation carried forward

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Measured Values

	Exenatide BID	Placebo
Number of Participants Analyzed [units:participants]	26	25
Change in mean 24-hour heart rate from baseline to endpoint [units: beats per minute] Least Squares Mean (Standard Error)
Baseline (Week 0)	74.83 (2.04)	74.47 (2.08)
Change at endpoint (Week 12)	2.14 (1.39)	-0.71 (1.42)

Statistical Analysis 1 for Change in mean 24-hour heart rate from baseline to endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.1585

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Approximately 25 subjects were intended to be randomized to both the exenatide and placebo arms. Assuming an approximate 24% dropout rate, 19 patients per treatment arm would complete the study. A sample of 19 patients per treatment group would provide 90% power to detect a 10 bpm difference between treatment groups in change in daily mean heart rate from baseline.
[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.

2. Secondary Outcome Measure: Change in daytime heart rate from baseline to endpoint [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Change in daytime heart rate from baseline to endpoint
Measure Description	Change from baseline to endpoint in daytime heart rate as measured by an ambulatory blood pressure monitor
Time Frame	12 weeks
Safety Issue?	No

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.
Intent to treat; Last observation carried forward

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Measured Values

	Exenatide BID	Placebo
Number of Participants Analyzed [units:participants]	26	25
Change in daytime heart rate from baseline to endpoint [units: beats per minute] Least Squares Mean (Standard Error)
Baseline (Week 0)	75.97 (2.22)	75.37 (2.26)
Change at endpoint (Week 12)	2.35 (1.59)	-0.87 (1.62)

Statistical Analysis 1 for Change in daytime heart rate from baseline to endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.1624

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Power calculation for the primary endpoint is described as part of the primary endpoint information above.
[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.

3. Secondary Outcome Measure: Change in nighttime (2400-0600) heart rate from baseline to endpoint [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Change in nighttime (2400-0600) heart rate from baseline to endpoint
Measure Description	Change from baseline to endpoint in nighttime (2400-0600) heart rate as measured by an ambulatory blood pressure monitor
Time Frame	12 weeks
Safety Issue?	No

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.
Intent to treat; Last observation carried forward

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Measured Values

	Exenatide BID	Placebo
Number of Participants Analyzed [units:participants]	26	25
Change in nighttime (2400-0600) heart rate from baseline to endpoint [units: beats per minute] Least Squares Mean (Standard Error)
Baseline (Week 0)	71.54 (2.12)	71.77 (2.16)
Change at endpoint (Week 12)	1.43 (1.79)	-0.28 (1.83)

Statistical Analysis 1 for Change in nighttime (2400-0600) heart rate from baseline to endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.5077

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Power calculation for the primary endpoint is described as part of the primary endpoint information above.
[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.

4. Secondary Outcome Measure: Change in mean 24 hour systolic blood pressure from baseline to endpoint [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Change in mean 24 hour systolic blood pressure from baseline to endpoint
Measure Description	Change from baseline to endpoint in average systolic blood pressure measured over 24 hours by an ambulatory blood pressure monitor
Time Frame	12 weeks
Safety Issue?	No

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.
Intent to treat; Last observation carried forward

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Measured Values

	Exenatide BID	Placebo
Number of Participants Analyzed [units:participants]	26	25
Change in mean 24 hour systolic blood pressure from baseline to endpoint [units: mmHg] Least Squares Mean (Standard Error)
Baseline (Week 0)	126.61 (3.04)	119.93 (3.10)
Change at endpoint (Week 12)	-0.81 (2.67)	-0.34 (2.72)

Statistical Analysis 1 for Change in mean 24 hour systolic blood pressure from baseline to endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.9034

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Power calculation for the primary endpoint is described as part of the primary endpoint information above.
[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. Secondary Outcome Measure: Change in mean 24 hour diastolic blood pressure from baseline to endpoint [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Change in mean 24 hour diastolic blood pressure from baseline to endpoint
Measure Description	Change from baseline to endpoint in average diastolic blood pressure measured over 24 hours by an ambulatory blood pressure monitor
Time Frame	12 weeks
Safety Issue?	No

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.
Intent to treat; Last observation carried forward

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Measured Values

	Exenatide BID	Placebo
Number of Participants Analyzed [units:participants]	26	25
Change in mean 24 hour diastolic blood pressure from baseline to endpoint [units: mmHg] Least Squares Mean (Standard Error)
Baseline (Week 0)	75.70 (2.05)	70.54 (2.09)
Change at endpoint (Week 12)	-0.60 (1.49)	-2.34 (1.52)

Statistical Analysis 1 for Change in mean 24 hour diastolic blood pressure from baseline to endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.4270

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Power calculation for the primary endpoint is described as part of the primary endpoint information above.
[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.

6. Secondary Outcome Measure: Change in hemoglobin A1c (HbA1c) from baseline to endpoint [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Change in hemoglobin A1c (HbA1c) from baseline to endpoint
Measure Description	Change from baseline to endpoint in HbA1c
Time Frame	12 weeks
Safety Issue?	No

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.
Intent to treat; Last observation carried forward

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Measured Values

	Exenatide BID	Placebo
Number of Participants Analyzed [units:participants]	27	25
Change in hemoglobin A1c (HbA1c) from baseline to endpoint [units: percent] Least Squares Mean (Standard Error)
Baseline (Week 0)	7.50 (0.16)	7.11 (0.17)
Change at endpoint (Week 12)	-0.15 (0.16)	0.12 (0.17)

Statistical Analysis 1 for Change in hemoglobin A1c (HbA1c) from baseline to endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.2600

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Power calculation for the primary endpoint is described as part of the primary endpoint information above.
[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.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Serious Adverse Events

Exenatide BID

Placebo

Total, serious adverse events

# participants affected / at risk

1/---

Injury, poisoning and procedural complications

Rib fracture¹,^†

# participants affected / at risk

1/---

0/---

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/---

1/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Exenatide BID	5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study.
Placebo	Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm).

Other Adverse Events

Exenatide BID

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

18/---

21/---

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

10/---

5/---

Nervous system disorders

Headache¹,^†

# participants affected / at risk

5/---

4/---

Infections and infestations

Influenza¹,^†

# participants affected / at risk

5/---

7/---

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

2/---

0/---

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain¹,^†

# participants affected / at risk

2/---

1/---

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

2/---

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/---

2/---

Metabolism and nutrition disorders

Hyperglycemia¹,^†

# participants affected / at risk

1/---

5/---

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/---

2/---

Nervous system disorders

Migraine¹,^†

# participants affected / at risk

0/---

2/---

Nervous system disorders

Restlessness¹,^†

# participants affected / at risk

0/---

2/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

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
No text entered.

Results Point of Contact

Name/Title:	Peter Ohman, Medical Science Director
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center Support Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Chief Medical Officer

Eli Lilly and Company

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries