Proof of Concept in Patients with Generalized Anxiety Disorder (GAD)AZD7325

Study identifier:D1140C00014

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multi-Center, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Phase II Study of 2 Oral Dose Groups of AZD7325, with a Lorazepam Arm, in Subjects with Generalized Anxiety Disorder (GAD)

Medical condition

Anxiety Disorders

Phase

Phase 2

Healthy volunteers

Study drug

AZD7325, Lorazepam, Placebo

Sex

All

Actual Enrollment

369

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 01 Dec 2008

Primary Completion Date: 01 May 2009

Study Completion Date: 01 May 2009

Study design

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

Verification:

Verified 01 Sept 2010 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

LITTLE ROCK, AR, United States

Location

Research Site

MESA, AZ, United States

Location

Research Site

CARSON, CA, United States

Location

Research Site

ESCONDIDO, CA, United States

Location

Research Site

GLENDALE, CA, United States

Location

Research Site

IRVINE, CA, United States

Location

Research Site

REDLANDS, CA, United States

Location

Research Site

RIVERSIDE, CA, United States

Arms	Assigned Interventions
Experimental: A AZD7325 5mg twice daily	Drug: AZD7325 4 tablets and 1 capsule taken twice a day for 28 days
Experimental: B AZD7325 15mg twice daily	Drug: AZD7325 4 tablets and 1 capsule taken twice a day for 28 days
Active Comparator: C Lorazepam 2mg twice daily	Drug: Lorazepam 4 tablets and 1 capsule taken twice a day for 28 days
Placebo Comparator: D Placebo	Drug: Placebo 4 tablets and 1 capsule taken twice a day for 28 days

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
International multi-center study, 43 sites recruited between Dec 2008 and May 2009

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening for eligibility and wash-out of restriced medications

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Participant Flow: Overall Study

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
STARTED	93	92	92	92
COMPLETED	66	67	78	77
NOT COMPLETED	27	25	14	15
Adverse Event	12	12	5	4
Protocol Violation	4	5	3	3
Withdrawal by Subject	5	4	1	4
Lost to Follow-up	4	0	2	1
Lack of Efficacy	0	0	1	2
Intake of prohibited medicine	0	0	2	0
All other reasons (not provided)	2	4	0	1

Baseline Characteristics

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

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Baseline Measures

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo	Total
Number of Participants [units: Participants]	93	92	92	92	369
Age, Customized [units: Participants]
18-39 years	46	42	43	44	175
40-65 years	47	50	49	48	194
Gender, Male/Female [units: Participants]
Female	58	43	45	45	191
Male	35	49	47	47	178

Outcome Measures

1. Primary Outcome Measure: Change in the Hamilton Rating Scale for Anxiety (HAM-A) total score [ Time Frame: Baseline to week 4 ]

Measure Type	Primary
Measure Name	Change in the Hamilton Rating Scale for Anxiety (HAM-A) total score
Measure Description	HAM-A total score 0-56 units, 14 questions scored on scale of 0-4 (0= Not present, 4=Very severe) . Higher HAM-A scores indicate higher levels of anxiety Change : score at week 4 minus score at randomization
Time Frame	Baseline to week 4
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.

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Measured Values

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
Number of Participants Analyzed [units:participants]	89	89	91	90
Change in the Hamilton Rating Scale for Anxiety (HAM-A) total score [units: Units on scale] Least Squares Mean (Standard Error)	-10.1 (0.89)	-10.4 (0.89)	-10.8 (0.88)	-9.5 (0.88)

No statistical analysis provided for Change in the Hamilton Rating Scale for Anxiety (HAM-A) total score

2. Secondary Outcome Measure: Change in Hospital Anxiety and Depression Scale for anxiety (HADS-A) total score [ Time Frame: Baseline to week 4 ]

Measure Type	Secondary
Measure Name	Change in Hospital Anxiety and Depression Scale for anxiety (HADS-A) total score
Measure Description	HADS-A total score 0-21 units, 0 is the best, Higher total scores indicate a higher severity of the mood or anxiety disorder Change : score at week 4 minus score at randomization
Time Frame	Baseline to week 4
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.

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Measured Values

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
Number of Participants Analyzed [units:participants]	89	89	91	90
Change in Hospital Anxiety and Depression Scale for anxiety (HADS-A) total score [units: Units on scale] Least Squares Mean (Standard Error)	-5.0 (0.51)	-4.9 (0.51)	-5.0 (0.51)	-4.5 (0.50)

No statistical analysis provided for Change in Hospital Anxiety and Depression Scale for anxiety (HADS-A) total score

3. Secondary Outcome Measure: Change in psychic anxiety factor as measured by HAM-A psychic cluster score [ Time Frame: Baseline to week 4 ]

Measure Type	Secondary
Measure Name	Change in psychic anxiety factor as measured by HAM-A psychic cluster score
Measure Description	The HAM-A psychic anxiety cluster score 0-28 units consists of 7 questions scored on scale of 0-4 (0=Not present, 4=Very severe) . Higher scores indicate higher levels of psychic anxiety disorder. Change: score at week 4 minus score at randomization
Time Frame	Baseline to week 4
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.

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Measured Values

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
Number of Participants Analyzed [units:participants]	89	89	91	90
Change in psychic anxiety factor as measured by HAM-A psychic cluster score [units: Units on scale] Least Squares Mean (Standard Error)	-5.5 (0.51)	-5.7 (0.51)	-6.0 (0.51)	-5.1 (0.51)

No statistical analysis provided for Change in psychic anxiety factor as measured by HAM-A psychic cluster score

4. Secondary Outcome Measure: Change in somatic symptoms as measured by HAM-A somatic cluster score [ Time Frame: Baseline to week 4 ]

Measure Type	Secondary
Measure Name	Change in somatic symptoms as measured by HAM-A somatic cluster score
Measure Description	The HAM-A Somatic cluster score 0-28 units consists of 7 questions scored on scale of 0-4 (0=Not present, 4=Very severe ) . Higher scores indicate higher levels of psychic anxiety disorder.
Time Frame	Baseline to week 4
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.

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Measured Values

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
Number of Participants Analyzed [units:participants]	89	89	91	90
Change in somatic symptoms as measured by HAM-A somatic cluster score [units: Units on scale] Least Squares Mean (Standard Error)	-4.5 (0.43)	-4.7 (0.43)	-4.9 (0.43)	-4.3 (0.43)

No statistical analysis provided for Change in somatic symptoms as measured by HAM-A somatic cluster score

5. Secondary Outcome Measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) percent maximum total score [ Time Frame: Baseline to week 4 ]

Measure Type	Secondary
Measure Name	Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) percent maximum total score
Measure Description	Q-LES-Q total score is the sum of the first 14 times of Q-LES-Q, and this total score is converted to a % maximum total score by : Q-LES-Q total score /70 x 100%, Larger values indicate a higher perceived quality of life enjoyment and satisfaction. Change : percentage at week 4 minus percentage at randomization
Time Frame	Baseline to week 4
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.

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Measured Values

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
Number of Participants Analyzed [units:participants]	88	89	91	90
Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) percent maximum total score [units: percentage] Least Squares Mean (Standard Error)	7.79 (1.339)	9.04 (1.338)	7.46 (1.318)	6.95 (1.317)

No statistical analysis provided for Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) percent maximum total score

Serious Adverse Events

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

Reporting Groups

	Description
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Serious Adverse Events

	AZD7325 5 mg	AZD7325 15 mg	Lorazepam	Placebo
Total, serious adverse events
# participants affected / at risk	0/93 (0.00%)	0/92 (0.00%)	0/92 (0.00%)	0/92 (0.00%)

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
AZD7325 5 mg	AZD7325 5 mg twice daily (BID)
AZD7325 15 mg	AZD7325 15 mg twice daily (BID)
Lorazepam	Lorazepam 2 mg twice daily (BID)
Placebo	Placebo

Other Adverse Events

AZD7325 5 mg

AZD7325 15 mg

Lorazepam

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

63/93 (67.74%)

59/92 (64.13%)

65/92 (70.65%)

51/92 (55.43%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

11/93 (11.83%)

8/92 (8.70%)

7/92 (7.61%)

8/92 (8.70%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

3/93 (3.23%)

7/92 (7.61%)

5/92 (5.43%)

Gastrointestinal disorders

Dry Mouth¹,^†

# participants affected / at risk

4/93 (4.30%)

5/92 (5.43%)

6/92 (6.52%)

3/92 (3.26%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/93 (3.23%)

1/92 (1.09%)

2/92 (2.17%)

5/92 (5.43%)

General disorders

Fatigue¹,^†

# participants affected / at risk

10/93 (10.75%)

2/92 (2.17%)

15/92 (16.30%)

8/92 (8.70%)

General disorders

Feeling Abnormal¹,^†

# participants affected / at risk

5/93 (5.38%)

8/92 (8.70%)

4/92 (4.35%)

3/92 (3.26%)

General disorders

Feeling Drunk¹,^†

# participants affected / at risk

5/93 (5.38%)

4/92 (4.35%)

5/92 (5.43%)

0/92 (0.00%)

Infections and infestations

Upper Respiratory Tract Infection¹,^†

# participants affected / at risk

2/93 (2.15%)

5/92 (5.43%)

1/92 (1.09%)

6/92 (6.52%)

Metabolism and nutrition disorders

Increased Appetite¹,^†

# participants affected / at risk

5/93 (5.38%)

0/92 (0.00%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

31/93 (33.33%)

27/92 (29.35%)

14/92 (15.22%)

11/92 (11.96%)

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

18/93 (19.35%)

16/92 (17.39%)

29/92 (31.52%)

11/92 (11.96%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

8/93 (8.60%)

8/92 (8.70%)

11/92 (11.96%)

Nervous system disorders

Sedation¹,^†

# participants affected / at risk

3/93 (3.23%)

6/92 (6.52%)

7/92 (7.61%)

1/92 (1.09%)

Psychiatric disorders

Euphoric Mood¹,^†

# participants affected / at risk

8/93 (8.60%)

7/92 (7.61%)

4/92 (4.35%)

1/92 (1.09%)

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

5/93 (5.38%)

3/92 (3.26%)

1/92 (1.09%)

Psychiatric disorders

Mood Altered¹,^†

# participants affected / at risk

5/93 (5.38%)

4/92 (4.35%)

0/92 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
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:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=251&filename=CSR-D1140C00014.pdf
Download
CSR-D1140C00014.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

Quintiles Worldwide

clinical.studies.ns@quintiles.com

Investigators

Principal Investigator

Mark A. Smith

AstraZeneca Pharmaceuticals

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=251&filename=CSR-D1140C00014.pdf

CSR-D1140C00014.pdf

Trial Results Summaries