Generalized Anxiety Disorder Proof of Concept Efficacy and Safety Study of SEP-225441 (Eszopiclone) In GAD Subjects

Study Overview
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Brief Summary
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To determine the safety and efficacy of SEP-225441 (eszopiclone) in subjects with generalized anxiety disorder (GAD).

Detailed Description
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This is a multicenter, randomized, double blind, placebo controlled study of the safety and efficacy of SEP-225441 (eszopiclone) in male and female adult subjects with a diagnosis of generalized anxiety disorder (GAD). The study consists of a screening period of 7-10 days, 8 weeks of treatment, and a 7 day follow-up period. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Official Title
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A Double Blind, Randomized, Placebo Controlled, Multicenter Study Examining the Efficacy and Safety of SEP-225441 in Subjects With Generalized Anxiety Disorder.

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: eszopiclone
* Drug: eszopiclone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects must be between 18 and 50 years of age Subjects must have GAD Subjects must be in otherwise good general health Exclusion Criteria: Subject has a documented history of HIV, hepatitis B or hepatitis C. Subject has a recent history (within 6 months of study entry) or current diagnosis of Major Depressive Disorder, panic disorder (or 3 or more panic attacks in the past month). Post Traumatic Stress Disorder, body dysmorphic disorder, eating disorder, or other disorder. Subject has a history or presence of Obsessive-Compulsive Disorder (OCD), any psychotic, bipolar or schizophrenic disorder. Subject has presence or history of antisocial personality or other severe disorder Subject has refractory GAD (previously unresponsive to 2 or more adequate courses of SSRI, SNRI, benzodiazepine or non-benzodiazepine treatment for GAD). Subject has history of seizures, including febrile seizures. Subject has initiated psychotherapeutic intervention with 30 days; however, continued psychotherapy is allowed if stable and not specifically directed at GAD. Subject is undergoing or has undergone electroconvulsive therapy. Subject is a current smoker or has smoked within the last 12 months. Subject has donated blood within the past 30 days or plans to donate during and within 30 days after study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>SEP-225441 (eszopiclone) total daily dose of 1.5 mg | Drug: eszopiclone<br>* SEP-225441 (eszopiclone) total daily dose of 1.5 mg<br>* Other names: SEP-225441;|
| Active Comparator: 2<br>SEP-225441 (eszopiclone) total daily dose of 0.9 mg | Drug: eszopiclone<br>* SEP-225441 (eszopiclone) total daily dose of 0.9 mg<br>* Other names: SEP-225441;|
| Placebo Comparator: 3<br>Placebo total daily dose 0.9 mg | Drug: Placebo<br>* Placebo total daily dose 0.9 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 8 in the Total Score on the Hamilton Anxiety Scale (HAM-A), as Assessed by the Site-trained Rater | THe HAM-M was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-M rating scale. These items included: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a 5-point scale (0-4). The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Hamilton Anxiety Scale (HAM-A) Total Score (Except for Week 8) | The HAM-A was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items included: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. all items are measured on a 5-point scale (0-4). Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms. | Baseline, Weeks 2, 4, 6 based on last observation carried forward (LOCF) | 
| Change in Individual Item Scores on HAM-A | The HAM-A was administered by a site trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items include: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a t5-point scale (0-4). Each HAM-A individual item score can range from 0 to 4 with higher scores indicating higher severity of anxiety questions. | Baseline, Weeks 2, 4, 6, 8 | 
| Change From Baseline in Clinician Global Impression of Severity (CGI-S) | The CGI-Swas completed by a board certified psychiatrist and represents the clinician's subjective assessment of severity of the subject's anxiety symptoms as assessed by a 7-scale score for a single question, Considering your total clinical experience with this particular population, how anxious is the subject at this time? The score was based on the following scale: 1=normal, not at all anxious; 2=borderline anxious; 3=mildly anxious; 4=moderately anxious; 5=markedly anxious; 6=severly anxious; 7=among the most extremely anxious subjects. CGI-S score can range from 0 to 7, with higher values indicating higher severity. | Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF) | 
| Clinical Global Impression- Improvement (CGI-I) | CGI-I was completed by a board certified psychiatrist and represented the clinician's subjective assessment of improvement of the subject's anxiety symptoms based on the following question, Compared to his/her condition at Visit 2, how much has he/she changed? The score was based on the following scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. CGI-I score can range from 0 to 7, with higher values indicating less improvement. | Weeks 2, 4, 6, 8, and 9, based on last observation carried forward (LOCF) | 
| Hamilton Anxiety Scale (HAM-A) 50% Anxiolytic Response | The HAM-A was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items include: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a 5-point scale (0-4). A 50% anxiolytic response was defined as a 50% or greater reduction from baseline in the HAM-A total score. The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms. | Week 2, 4, 6, 8 | 
| Hamilton Anxiety Scale (HAM-A) Remission | The HAM-A was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items include: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a 5-point scale (0-4). Remission was defined as a HAM-A total score of 7 or less. The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms. | Week 2, 4, 6, 8 based on last observation carried forward (LOCF) | 
| Change From Baseline on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form | The Q-LES-Q was completed by the subject and assessed quaility of life based on 16 items, each evaluated on a 5-point scale of overall level of enjoyment/satisfaction: 1=very poor; 2=poor; 3=fair; 4=good; 5=very good. The overall percentage score was computed as a sum of items 1 to 14 as expressed as a percentage of the maximum possible score: Overall Percentage Score = Sum [item 1... item 14]-14)/(70-14 ) *100%. Q-LES-Q overall percentage score can range from 0 to 100, with higher values indicating higher quality of life. | Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF) | 
| Change From Baseline Insomnia Severity Index (ISI) Total Score | The ISI was completed by the subject and is an assessment of the severity of insomnia. The administered extended ISI questionnaire consists of 5 items (containing 7 questions, as item 1 contains 3 questions) comprising the original ISI questionnaire, plus 6 quality of life related items (sleep quality, restedness/refreshness upon arising, daytime fatigue, attention/concentration, relationships and mood disturbances), and 2 items assessing duration and frequency of sleep problems. All items, except for the insomnia duration and frequency questions, are measured on a Likert-type 5-point scale (0-4). ISI total score can range from 0 to 28, with higher scores indicating more severe insomnia. | Baseline, Weeks 2, 4, 6, 8, based on lst observation carried forward (LOCF) | 
| Change From Baseline Sheehan Disability Scale (SDS) | The SDS was completed by the subject and captured the subject's level of disability. The subject rated the extent to which his or her work, social life or leisure activities, and home life or family responsibilities were impaired by his or her symptoms on a 10-point visual analog scale. SDS total score can range from 0 to 30, with higher scores indicating higher functional impairment. | Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF) | 
| Change From Baseline Epworth Sleepiness Scale (ESS) | ESS was completed by the subject and assessed daytime sedation based on 8 items, each presenting a situation for which the subject needed to evaluate how likely he/she is to doze off or fall asleep in contrast to feeling just tired. Each item was evaluated on the following scale: 0 = would never doze; 1 = slight chance of dozing; 2 = moderate chance of dozing; 3 = high chance of dozing. ESS total score can range from 0 to 24, with higher scores indicating higher levels of daytime sleepiness. | Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anxiety