Generalized Anxiety Disorder Adjunct Study

A Multicenter, Rand., Double-blind, Parallel-group, Pbo-controlled Study of the Efficacy and Safety of SEROQUEL® XR Compared With Pbo as an Adjunct to Treatment in Patients With Generalized Anxiety Disorder Who Demonstrate Partial or No Response to a SSRI or SNRI Alone or in Combination With a Benzo

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00534599

Enrollment

409

Registered

2007-09-26

Start date

2007-08-31

Completion date

2008-09-30

Last updated

2011-04-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anxiety, Anxiety Disorders, Anxiety Neuroses, Anxiety States

Keywords

Generalized anxiety disorders, anxiety, adjunct treatment in anxiety, anxiety disorder, partial or non-responder in anxiety

Brief summary

This study is being carried out to see if extended release quetiapine fumarate (Seroquel®XL) when added to standard selective serotonin reuptake inhibitor (SSRI) / serotonin-norepinephrine reuptake inhibitor (SNRI) therapy is effective and safe for the treatment of Generalized Anxiety Disorder in patients with partial or no response to SSRI/SNRI alone or in combination with a benzodiazepine, and if so, how it compares with placebo

Interventions

DRUGPlacebo

oral

DRUGquetiapine fumarate XR

oral

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

Provision of Informed Consent * Documented diagnosis of Generalized Anxiety Disorder * Female patients must not be pregnant and be willing to use a reliable method of birth control * Be able to understand and comply with study requirements

Exclusion criteria

Other psychiatric disorders that could confound the study results, as judged by the study doctor * Moderate to severe depression * Other clinically relevant diseases, as judged by the study doctor * Medication that you are taking, as judged by the study doctor

Design outcomes

Primary

Measure	Time frame	Description
Least Square Mean Change From Randomization to Week 8 in Hamilton Rating Scale for Anxiety (HAM-A) Total Score	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) consists of 14 items to evaluate anxiety. Each item is rated on a scale from 0-4, with '0' showing no anxiety (not present) and '4' showing the worst (very severe). Results based on MITT population with available data for this outcome measure. Least square mean of each treatment was adjusted for baseline value.

Secondary

Measure	Time frame	Description
Number of Patients With Clinical Global Impression-Global Improvement (CGI-I) Score of Much/Very Much Improved at Week 8	Baseline (randomization) and then 8 weeks	This pertains to the CGI-I scale which rates improvement of anxiety on a scale from 1-7, with '1' showing the best improvement(Very Much Improved) and '7' showing the worst improvement (Very Much Worse) as compared to the baseline visit. A rating of '2' indicates 'Much Improved'. Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 8 in HAM-A Psychic Anxiety Subscale Score	Baseline (randomization) and then 8 weeks	The HAM-A psychic anxiety factor subscale is defined as the sum of the following 7 HAM-A factors: anxious mood, tension, fears, insomnia, intellectual, depressed mood and behavior at the interview (i.e.items 1-6 and 14, respectively) Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 8 in HAM-A Somatic Anxiety Subscale Score	Baseline (randomization) and then 8 weeks	The HAM-A Somatic cluster subscale is defined as the sum of the following 7 HAM-A items: somatic (muscular), somatic (sensory), cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms and autonomic system (i.e. items 7-13 respectively). Results based on MITT population with available data for this outcome measure.
Number of Patients With HAM-A Response (≥50% Score Reduction From Randomization) at Week 8	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) response is derived from the HAM-A total score and is defined as a decrease from baseline total HAM-A score of at least 50%. (1=Yes, 0=No) Results based on MITT population with available data for this outcome measure.
Number of Patients With HAM-A Remission (Total Score ≤7) at Week 8	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) remission is derived from the HAM-A total score and is defined as a HAM-A total score of ≤7. 1=Yes, 0=No Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 8 in Quality of Life Enjoyment and Satisfaction Questionaire (Q-LES-Q) Percent Maximum Total Score	Baseline (randomization) and then 8 weeks	The Q-LES-Q score is the sum of the first 14 items, larger values indicating a higher perceived quality of life enjoyment and satisfaction. This total score was converted to a % maximum score using the following scoring conversion: %Maximum score = (Total score-14)\*(100/560)rounded to an integer. Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 8 in Clinical Global Impression-Severity of Illness (CGI-S) Score	Baseline (randomization) and then 8 weeks	The CGI-S is assessed on a seven-point scale ranging from most extremely ill/very much worse (7) to normal/very much improved (1). Results based on MITT population with available data for this outcome measure.
Mean Change From Randomization to Week 8 in Q-LES-Q Item 16 (Overall Quality of Life) Score	Baseline (randomization) and then 8 weeks	Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 1 in HAM-A Total Score	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) consists of 14 items to evaluate anxiety. Each item is rated on a scale from 0-4, with '0' showing no anxiety (not present) and '4' showing the worst (very severe). Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 1 in HAM-A Psychic Anxiety Subscale Score	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) consists of 14 items to evaluate anxiety. Each item is rated on a scale from 0-4, with '0' showing no anxiety (not present) and '4' showing the worst (very severe).Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 1 in HAM-A Somatic Anxiety Subscale Score	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) consists of 14 items to evaluate anxiety. Each item is rated on a scale from 0-4, with '0' showing no anxiety (not present) and '4' showing the worst (very severe). Results based on MITT population with available data for this outcome measure.
Least Square Mean Change From Randomization to Week 1 in CGI-S Score	Baseline (randomization) and then 8 weeks	Results based on MITT population with available data for this outcome measure.
Number of Patients With HAM-A Response (≥50% Score Reduction From Randomization) at Week 1	Baseline (randomization) and then 8 weeks	Hamilton Rating Scale for Anxiety (HAM-A) consists of 14 items to evaluate anxiety. Each item is rated on a scale from 0-4, with '0' showing no anxiety (not present) and '4' showing the worst (very severe). Results based on MITT population with available data for this outcome measure.
Mean Change From Randomization to Week 8 in Q-LES-Q Item 15 (Satisfaction With Medication) Score	Baseline (randomization) and then 8 weeks	Results based on MITT population with available data for this outcome measure.

Countries

United States

Participant flow

Recruitment details

Patient enrollment from 31 August 2007 to 02 September 2008

Pre-assignment details

Wash-out period of up to 35 days for discontinuation of prohibited medications

Participants by arm

Arm	Count
Quetiapine XR 50 mg to 300 mg extended release tablets once daily	204
Placebo Matching placebo tablets once daily	198
Total	402

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	25	4
Overall Study	Developed study-specific d/c criteria	5	0
Overall Study	Generalized anxiety disorder worsened	0	1
Overall Study	Incorrect enrollment	2	1
Overall Study	Lack of Efficacy	0	1
Overall Study	Lost to Follow-up	11	14
Overall Study	Mis-randomization	2	2
Overall Study	Other	7	0
Overall Study	Protocol Violation	1	3
Overall Study	Withdrawal by Subject	4	6

Baseline characteristics

Characteristic	Quetiapine XR	Placebo	Total
Age Continuous	46.6 Years STANDARD_DEVIATION 12.1	44.2 Years STANDARD_DEVIATION 10.9	44.4 Years STANDARD_DEVIATION 11.5
Sex: Female, Male Female	146 Participants	150 Participants	296 Participants
Sex: Female, Male Male	58 Participants	48 Participants	106 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	154 / 209	120 / 200
serious Total, serious adverse events	0 / 209	0 / 200

Outcome results

Primary

Least Square Mean Change From Randomization to Week 8 in Hamilton Rating Scale for Anxiety (HAM-A) Total Score

Hamilton Rating Scale for Anxiety (HAM-A) consists of 14 items to evaluate anxiety. Each item is rated on a scale from 0-4, with '0' showing no anxiety (not present) and '4' showing the worst (very severe). Results based on MITT population with available data for this outcome measure. Least square mean of each treatment was adjusted for baseline value.