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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00808249
• Collaborator: (none)
• Enrollment: 725
• Locations: 52
• Arms: 4
• Duration (Months): 5
• Patients Per Site: 13.9
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine whether AstraZeneca's drug AZD7325 is safe and effective in the treatment of generalized anxiety disorder.

Condition or Disease	Intervention/Treatment	Phase
Anxiety Disorders	Drug: AZD7325; Drug: AZD7325; Drug: AZD7325; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 725 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Efficacy and Safety Study of AZD7325 in the Treatment of Generalized Anxiety Disorder (GAD)
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A-AZD7325 2mg AZD7325 2mg BID	Drug: AZD7325; 2 tablets taken twice a day for 28 days
Experimental: B-AZD7325 5mg AZD7325 5mg BID	Drug: AZD7325; 2 tablets taken twice a day for 28 days
Experimental: C-AZD7325 10mg AZD7325 10mg QD	Drug: AZD7325; 2 tablets taken twice a day for 28 days
Experimental: D-Placebo Placebo	Drug: Placebo; 2 tablets taken twice a day for 28 days

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score [From randomization (baseline) to week 4]

   The HAM -A is a 14-item clinician administered scale for the evaluation of anxiety symptoms. Each HAM-A item is rated on a 0 (not present) to 4 (very severe) scale, higher score indicates high level of anxiety. The HAM-A total score is calculated as the sum of 14 individual scores, with 56 as the maximum.

Secondary Outcome Measures

1. Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score [From randomization (baseline) to week 4]

   The HADS-A is a 7 item, self administered instrument to measure level of anxiety. Each item is a score rate from 0 (happens rarely ) to 3 (happens frequently), and the items are totaled for a maximum score of 21. The mimimum score 0 indicates that the patient rarely suffered from anxiety symptoms.

2. Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score [From baseline (randomization) to week 4]

   The HAM-A psychic anxiety factor score is calculated as the sum of 7 HAM-A individual items related with psychic anxiety ( each rated from 0 to 4, 0 is the best). The minimum score for HAM-A psychic anxiety factor is 0 and maximum score is 28, higher score indicates severe psychic anxiety symptoms.

3. Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score [From baseline ( randomization) to week 4]

   The HAM-A somatic factor score is calculated as the sum of 7 individual HAM-A items (each is rated from 0 to 4, 0 is the best) related with somatic anxiety symptoms. The minimum score for HAM-A somatic factor is 0 and maximum score is 28, higher score indicates severe somatic anxiety symptoms

4. Change in Sheehan Disability Scale (SDS) Global Total Score [From baseline ( randomization) to week 4]

   The Sheehan Disability Scale is a patient-rated measure of functional disability in 3 subscales: work, social, and family life. Each subscale is rated from 0 to 10, with 0 as the best. SDS global total score is calculated as the sum of 3 subscales and ranges from 0(unimpaired) to 30 (highly impaired)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent before any study-related procedures start.

• The patient is previously diagnosed with Generalized Anxiety Disorder.

• The patient has a HADS-A (anxiety) score ≥10 at both screening and randomization.

Exclusion Criteria:

• Patient has a lifetime history of schizophrenia or other psychotic disorders

• Patient has a history of seizures or seizure disorder.

• Patient is pregnant or breast feeding.

• Patient has received electroconvulsive treatment (ECT) in the past.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Tucson	Arizona	United States
3	Research Site	Arcadia	California	United States
4	Research Site	Beverly Hills	California	United States
5	Research Site	Cerritos	California	United States
6	Research Site	Chino	California	United States
7	Research Site	Encino	California	United States
8	Research Site	Los Alamitos	California	United States
9	Research Site	Novato	California	United States
10	Research Site	Oceanside	California	United States
11	Research Site	San Diego	California	United States
12	Research Site	Norwich	Connecticut	United States
13	Research Site	Ft Myers	Florida	United States
14	Research Site	Miami	Florida	United States
15	Research Site	Pembroke Pines	Florida	United States
16	Research Site	St Petersberg	Florida	United States
17	Research Site	Tampa	Florida	United States
18	Research Site	Winter Park	Florida	United States
19	Research Site	Atlanta	Georgia	United States
20	Research Site	Marietta	Georgia	United States
21	Research Site	Smyrna	Georgia	United States
22	Research Site	Libertyville	Illinois	United States
23	Research Site	Park Ridge	Illinois	United States
24	Research Site	Indianapolis	Indiana	United States
25	Research Site	Overland Park	Kansas	United States
26	Research Site	Baltimore	Maryland	United States
27	Research Site	Boston	Massachusetts	United States
28	Research Site	Cambridge	Massachusetts	United States
29	Research Site	St. Louis	Missouri	United States
30	Research Site	Clementon	New Jersey	United States
31	Research Site	Fresh Meadows	New York	United States
32	Research Site	Mount Kisco	New York	United States
33	Research Site	New York	New York	United States
34	Research Site	Rochester	New York	United States
35	Research Site	Raleigh	North Carolina	United States
36	Research Site	Winston-salem	North Carolina	United States
37	Research Site	Bismarck	North Dakota	United States
38	Research Site	Beechwood	Ohio	United States
39	Research Site	Cincinnati	Ohio	United States
40	Research Site	Middleburg Heights	Ohio	United States
41	Research Site	Oklahoma City	Oklahoma	United States
42	Research Site	Portland	Oregon	United States
43	Research Site	Jenkintown	Pennsylvania	United States
44	Research Site	Norristown	Pennsylvania	United States
45	Research Site	Memphis	Tennessee	United States
46	Research Site	Friendswood	Texas	United States
47	Research Site	San Antonio	Texas	United States
48	Research Site	Salt Lake City	Utah	United States
49	Research Site	Woodstock	Vermont	United States
50	Research Site	Herndon	Virginia	United States
51	Research Site	Spokane	Washington	United States
52	Research Site	Middleton	Wisconsin	United States

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Mark A. Smith, MD, PhD, AstraZeneca
• Principal Investigator: David V. Sheehan, University of South Florida College of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00808249
• Other Study ID Numbers: D1140C00006
• First Posted: Dec 15, 2008
• Last Update Posted: Jun 20, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: Generalized Anxiety Disorder; GAD; Anxiety
• Additional relevant MeSH terms: Disease; Anxiety Disorders

Study Results

Participant Flow

Recruitment Details	International multi-center study, 44 sites recruited between Dec 2008 and May 2009
Pre-assignment Detail	Screening for eligibility and wash-out of restriced medications. 725 subjects enrolled but 424 subjects were randomized. Number of participants analyzed is the number of subjects in MITT (modified intent to treat) population, it is different with any of population listed in the participant flow chart.

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo
Period Title: Overall Study
STARTED	107	106	105	106
COMPLETED	90	91	83	90
NOT COMPLETED	17	15	22	16

Baseline Characteristics

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo	Total
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo	Total of all reporting groups
Overall Participants	107	106	105	106	424
Age, Customized (Number) [Number]
18-39	44 41.1%	43 40.6%	48 45.7%	53 50%	188 44.3%
40-65	63 58.9%	63 59.4%	57 54.3%	53 50%	236 55.7%
Sex: Female, Male (Count of Participants)
Female	62 57.9%	62 58.5%	61 58.1%	62 58.5%	247 58.3%
Male	45 42.1%	44 41.5%	44 41.9%	44 41.5%	177 41.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score
Description	The HAM -A is a 14-item clinician administered scale for the evaluation of anxiety symptoms. Each HAM-A item is rated on a 0 (not present) to 4 (very severe) scale, higher score indicates high level of anxiety. The HAM-A total score is calculated as the sum of 14 individual scores, with 56 as the maximum.
Time Frame	From randomization (baseline) to week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo
Measure Participants	105	105	103	102
Least Squares Mean (Standard Error) [Units on scale]	-10.9 (0.87)	-11.1 (0.86)	-11.5 (0.87)	-10.9 (0.88)

2. Secondary Outcome

Title	Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score
Description	The HADS-A is a 7 item, self administered instrument to measure level of anxiety. Each item is a score rate from 0 (happens rarely ) to 3 (happens frequently), and the items are totaled for a maximum score of 21. The mimimum score 0 indicates that the patient rarely suffered from anxiety symptoms.
Time Frame	From randomization (baseline) to week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo
Measure Participants	105	105	103	102
Least Squares Mean (Standard Error) [Units on scale]	-4.5 (0.49)	-4.2 (0.49)	-5.2 (0.50)	-4.6 (0.50)

3. Secondary Outcome

Title	Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score
Description	The HAM-A psychic anxiety factor score is calculated as the sum of 7 HAM-A individual items related with psychic anxiety ( each rated from 0 to 4, 0 is the best). The minimum score for HAM-A psychic anxiety factor is 0 and maximum score is 28, higher score indicates severe psychic anxiety symptoms.
Time Frame	From baseline (randomization) to week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo
Measure Participants	105	105	103	102
Least Squares Mean (Standard Error) [Unit on scale]	-5.9 (0.51)	-5.8 (0.51)	-6.5 (0.52)	-5.8 (0.52)

4. Secondary Outcome

Title	Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score
Description	The HAM-A somatic factor score is calculated as the sum of 7 individual HAM-A items (each is rated from 0 to 4, 0 is the best) related with somatic anxiety symptoms. The minimum score for HAM-A somatic factor is 0 and maximum score is 28, higher score indicates severe somatic anxiety symptoms
Time Frame	From baseline ( randomization) to week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo
Measure Participants	105	105	103	102
Least Squares Mean (Standard Error) [Units on scale]	-5.0 (0.41)	-5.3 (0.41)	-5.1 (0.42)	-5.2 (0.42)

5. Secondary Outcome

Title	Change in Sheehan Disability Scale (SDS) Global Total Score
Description	The Sheehan Disability Scale is a patient-rated measure of functional disability in 3 subscales: work, social, and family life. Each subscale is rated from 0 to 10, with 0 as the best. SDS global total score is calculated as the sum of 3 subscales and ranges from 0(unimpaired) to 30 (highly impaired)
Time Frame	From baseline ( randomization) to week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A-AZD7325 2 mg	B-AZD7325 5 mg	C-AZD7325 10 mg	D-Placebo
Arm/Group Description	AZD7325 2 mg BID	AZD7325 5 mg BID	AZD7325 10 mg QD	Placebo
Measure Participants	81	78	75	81
Least Squares Mean (Standard Error) [Units on scale]	-4.7 (0.79)	-5.7 (0.80)	-6.8 (0.82)	-6.8 (0.79)

Adverse Events

Adverse Event Reporting Description	Number at risk is number of patients in safety population. The participant flow shows patients randomized and completed the study. The numbers are not the same since 2 patients were randomized but did not take study drug.
Arm/Group Title	A-AZD7325 2 mg		B-AZD7325 5 mg		C-AZD7325 10 mg		D-Placebo
Arm/Group Description	AZD7325 2 mg BID		AZD7325 5 mg BID		AZD7325 10 mg QD		Placebo
All Cause Mortality
	A-AZD7325 2 mg		B-AZD7325 5 mg		C-AZD7325 10 mg		D-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	A-AZD7325 2 mg		B-AZD7325 5 mg		C-AZD7325 10 mg		D-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		1/ (NaN)		0/ (NaN)		0/ (NaN)
Injury, poisoning and procedural complications
Road Traffic Accident	0/106 (0%)		1/106 (0.9%)		0/105 (0%)		0/105 (0%)
Nervous system disorders
Grand Mal Convulsion	0/106 (0%)		1/106 (0.9%)		0/105 (0%)		0/105 (0%)
Psychiatric disorders
Anxiety	1/106 (0.9%)		0/106 (0%)		0/105 (0%)		0/105 (0%)
Vascular disorders
Deep Vein Thrombosis	1/106 (0.9%)		0/106 (0%)		0/105 (0%)		0/105 (0%)
Other (Not Including Serious) Adverse Events
	A-AZD7325 2 mg		B-AZD7325 5 mg		C-AZD7325 10 mg		D-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/ (NaN)		18/ (NaN)		32/ (NaN)		14/ (NaN)
Gastrointestinal disorders
Dry Mouth	6/106 (5.7%)		4/106 (3.8%)		11/105 (10.5%)		7/105 (6.7%)
Nausea	10/106 (9.4%)		9/106 (8.5%)		10/105 (9.5%)		8/105 (7.6%)
General disorders
Fatigue	8/106 (7.5%)		7/106 (6.6%)		5/105 (4.8%)		3/105 (2.9%)
Feeling Abnormal	1/106 (0.9%)		4/106 (3.8%)		8/105 (7.6%)		0/105 (0%)
Nervous system disorders
Dizziness	13/106 (12.3%)		18/106 (17%)		32/105 (30.5%)		12/105 (11.4%)
Headache	8/106 (7.5%)		17/106 (16%)		9/105 (8.6%)		14/105 (13.3%)
Sedation	5/106 (4.7%)		6/106 (5.7%)		10/105 (9.5%)		1/105 (1%)
Somnolence	13/106 (12.3%)		9/106 (8.5%)		17/105 (16.2%)		6/105 (5.7%)
Psychiatric disorders
Euphoric Mood	7/106 (6.6%)		11/106 (10.4%)		10/105 (9.5%)		6/105 (5.7%)
Insomnia	4/106 (3.8%)		5/106 (4.7%)		2/105 (1.9%)		7/105 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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