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

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

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

Study Overview

• Status: Completed
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: eszopiclone; Drug: eszopiclone; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 456
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35226
      • Birmingham Psychiatry Pharaceutical Studies, Inc.
  • California
    • Arcadia, California, United States, 91007
    • Beverly Hills, California, United States, 90210
      • Southwestern Research, Inc.
    • Burbank, California, United States, 91506
      • Southwestern Research, Inc.
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group
    • Glendale, California, United States, 91202
      • California Clinical Trials Medical Group
    • Newport Beach, California, United States, 92660
    • Oceanside, California, United States, 92056
      • Excell Research
    • Paramount, California, United States, 90723
      • California Clinical Trials Medical Group
    • Pasadena, California, United States, 91107
      • Southwestern Research, Inc.
    • San Diego, California, United States, 92123
      • California Clinical Trials Medical Group
    • Stanford, California, United States, 94302
      • Stanford Universtiy Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • University of CT Health Center
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care, Pc
  • Florida
    • Bradenton, Florida, United States, 34208
      • Florida Clinical Research Center LLC
    • Gainsville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
    • St. Petersburg, Florida, United States, 33702
      • Comprehensive NeuroScience, Inc.
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials, LLC
    • West Palm Beach, Florida, United States, 33407
      • Janus Center For Psychiatric Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Comprehensive NeuroScience, Inc.
    • Smyrna, Georgia, United States, 30080
      • Carmen Research
  • Illinois
    • Hoffman Estates, Illinois, United States, 60194
      • Alexian Brothers Center for Psychiatric Research
    • Park Ridge, Illinois, United States, 60068
      • Comprehensive NeuroScience, Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associats Clinical Research
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trials Technology, Inc.
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharasite Research, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Braintree, Massachusetts, United States, 02184
      • Coastal Research Associates, Inc.
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Clementon, New Jersey, United States, 08021
      • CRI Worldwide, LLC
  • New York
    • Brooklyn, New York, United States, 11235
      • Social Psychiatry Research Institute
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
    • Fresh Meadows, New York, United States, 11366
      • Comprehensive NeuroScience, Inc.
    • New York, New York, United States, 10021
      • Fieve Clinica Services, Inc.
    • New York, New York, United States, 10021
      • Medical & Behavioral Health Research, PC
    • New York, New York, United States, 10023
      • Medical & Behavioral Health Research, P.C.
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Glenwood Psychiatric Associates, P.L.L.C.
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Horizon Medical Services
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • North Coast Clinical Trials
    • Cincinnati, Ohio, United States, 45242
      • Patient Priority Clinical Sties, LLC
    • Dayton, Ohio, United States, 45408
      • Midwest Clinical Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Mdical Research, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Center for Clinical Investigations, Inc.
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide, LLC
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Rhode Island Mood & Memory Research Institute
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78756
      • Future Search Trials
    • Houston, Texas, United States, 77042
      • Carolos Guerra, Jr., M.D.
    • San Antonio, Texas, United States, 78229
      • San Antonio Psychiatric Research Center
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia, Center for Psychiatric Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sunovion

Publications and helpful links

General Publications

• Williams JB, Kobak KA, Giller E, Reasner DS, Curry L, Detke MJ. Comparison of Site-Based Versus Central Ratings in a Study of Generalized Anxiety Disorder. J Clin Psychopharmacol. 2015 Dec;35(6):654-60. doi: 10.1097/JCP.0000000000000422.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 4, 2008
• First Submitted That Met QC Criteria: February 14, 2008
• First Posted (Estimate): February 15, 2008

Study Record Updates

• Last Update Posted (Estimate): April 8, 2016
• Last Update Submitted That Met QC Criteria: March 10, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Anxiety
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: 194-027