Randomized Trial of Adult Participants With Generalized Anxiety Disorder

Phase 3

Completed

Conditions: Generalized Anxiety Disorder

Interventions: Drug: Troriluzole
Drug: Placebo

Registration Number: NCT03829241

Lead Sponsor: Biohaven Pharmaceuticals, Inc.

Brief Summary: The purpose of this study is to compare the efficacy of troriluzole versus placebo in participants with generalized anxiety disorder.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 881

Inclusion Criteria

Primary diagnosis of generalized anxiety disorder (GAD) either moderate or severe as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) as confirmed by the MINI at Screening, in addition to a psychiatric evaluation by a board- certified or Biohaven-approved board-eligible psychiatrist; The duration of illness must be ≥ 1 year
Hamilton Anxiety Rating Scale (HAM-A) Total Score of ≥ 18 at both Screening and Baseline
Clinical Global Impression of Severity Scale (CGI-S) score of ≥ 4 at both Screening and Baseline
Determined by the investigator to be medically stable at baseline/randomization as assessed by medical history, physical examination, laboratory test results, and electrocardiogram testing. Participants must be physically able and expected to complete the trial as designed
Minimum of 6 years of education or equivalent to complete necessary scales and understand consent forms
Participants must be able to understand and agree to comply with the prescribed dosage regimens and procedures; report for regularly scheduled office visits; and reliably communicate with study personnel about adverse events and concomitant medications
Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to dosing at Baseline

Exclusion Criteria

Participants with a primary DSM-V psychiatric disorder diagnosis other than GAD within the past 6-months. Note: Participants with a secondary diagnosis of comorbid social anxiety disorder or specific phobia are allowed, if in the investigator's judgement, the diagnosis is not sufficiently prominent and active so as to be confound the assessment of GAD symptoms
Participants should be excluded at screening or baseline if any medical or psychiatric condition other than GAD, as specified in the inclusion criteria, could predominantly explain or contribute significantly to the subjects' symptoms or that could confound assessment of GAD symptoms
Participants who report a history of inadequate response (per investigator judgement) to 3 or more adequate trials (including current trial) of any SSRI or SNRI, at an adequate dose and adequate duration (at least 8 weeks) for the treatment of GAD within the 3 years prior to randomization
Hamilton Depression Rating Scale 17 (HAM-D-17) item 1 of >1 at Screening or Baseline
HAM-D-17 of > 19 at Baseline
Any eating disorder within the last 12 months prior to Screening
Acute suicidality in the last 12 months, or suicide attempt or self-injurious behavior in the last 12 months prior to Screening
Score of >0 on the Sheehan Suicidality Tracking Scale for the period of 12 months prior to screening, and at baseline
History of psychosurgery, deep brain stimulation (DBS) or electroconvulsive therapy (ECT)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomization Phase (Weeks 1 through 8): Participants received troriluzole matching placebo capsules BID orally for up to 8 weeks in the DB randomization phase. Extension Phase (Weeks 9 through 56): Participants, who completed the randomization phase and for whom the investigator believed OL treatment could offer an acceptable risk-benefit profile, entered the extension phase and received OL troriluzole capsules (continuing on the same dose and regimen that was taken at the end of the randomization phase) for up to additional 48 weeks.
Placebo	Troriluzole	Randomization Phase (Weeks 1 through 8): Participants received troriluzole matching placebo capsules BID orally for up to 8 weeks in the DB randomization phase. Extension Phase (Weeks 9 through 56): Participants, who completed the randomization phase and for whom the investigator believed OL treatment could offer an acceptable risk-benefit profile, entered the extension phase and received OL troriluzole capsules (continuing on the same dose and regimen that was taken at the end of the randomization phase) for up to additional 48 weeks.
Troriluzole	Troriluzole	Randomization phase (Weeks 1 through 8): Participants received troriluzole 100 mg capsules twice daily (BID) orally for up to 8 weeks in the double-blind (DB) randomization phase. Extension phase (Weeks 9 through 56): Participants, who completed the randomization phase and for whom the investigator believed open-label (OL) treatment could offer an acceptable risk-benefit profile, entered the extension phase and received OL troriluzole capsules (continuing on the same dose and regimen that was taken at the end of the randomization phase) for up to additional 48 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the HAM-A Total Score at Week 8	Baseline, Week 8	The HAM-A was an investigator-administered scale and consisted of 14 items: anxious mood, tension, fears, insomnia, concentration, depressed mood, behavior at interview, somatic muscular, somatic sensory, cardiovascular, respiratory, gastrointestinal, genitourinary, and autonomic symptoms. Each item was scored on a scale of 0 (not present) to 4 (severe) with a total score range of 0-56. A decreased score indicated a decrease in anxiety symptoms.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and TEAEs Judged to be Related to Study Medication During Randomized Phase	From first dose to Week 8 plus 30 days (maximum duration: 12 weeks)	A serious adverse event (SAE) was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention. Treatment-emergent AEs (TEAEs) in the randomization phase included any adverse event (AE) with an onset date on or after the first day of double-blind study drug and up to the first day of open-label study drug in the extension phase (for participants entering the extension phase) or last day of the randomization phase study drug + 30 days.
Number of Participants With Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs Judged to be Related to Study Drug During Extension Phase	From Week 9 to the last dose of troriluzole in extension phase plus 30 days (maximum duration: 333 days)	An SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention. TEAEs in the extension phase included any AE with an onset date on or after the first day of the study drug in the extension phase and up to the last day of the study drug in the extension phase + 30 days.
Number of Participants With Clinically Significant Laboratory Abnormalities During the Randomization Phase	From first dose to Week 8 plus 30 days (maximum duration: 12 weeks)	Clinically significant laboratory abnormalities were defined as Grade 3 to 4 laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events (CTCAE) Version 5.0 (2017) or the Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017), where Grade 3=Severe and Grade 4=Potentially Life Threatening. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8	Baseline, Week 8	The SDS was assessed in 3 domains: work/school (0-10), social life (0-10), and family life (0-10). The score from each domain was summed into a single-dimensional measure of global functional impairment (SDS total score) that ranged from 0 (unimpaired) to 30 (highly impaired).
Change From Baseline in Clinical Global Impression of Severity Scale (CGI-S) Score at Week 8	Baseline, Week 8	Participants rated on the seven-point severity of Illness with severity of wherein 1 = normal, not at all; 2= borderline ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7 = among the most extremely ill participants.

Trial Locations

Locations (48): CalNeuro Research Group
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Los Angeles, California, United States
University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Boston Clinical Trials
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Boston, Massachusetts, United States
Baylor College of Medicine
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Houston, Texas, United States
Pacific Research Partners, LLC
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Oakland, California, United States
Altea Research Institute
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Las Vegas, Nevada, United States
CNS Network
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Torrance, California, United States
California Neuroscience Research Medical Group, Inc
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Sherman Oaks, California, United States
Phoenix Medical Research
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Prairie Village, Kansas, United States
iResearch Atlanta LLC
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Decatur, Georgia, United States
Gulfcoast Clinical Research Center
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Fort Myers, Florida, United States
Collaborative Neuroscience Network, LLC.
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Garden Grove, California, United States
University of California, San Francisco-Fresno
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Fresno, California, United States
Pacific Clinical Research Medical Group
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Upland, California, United States
Galiz Research
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Hialeah, Florida, United States
Harmony Clinical Research
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North Miami Beach, Florida, United States
Suburban Research Associates, Inc.
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Media, Pennsylvania, United States
Northwest Clinical Research Center
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Bellevue, Washington, United States
Keystone Clinical Studies, LLC
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Norristown, Pennsylvania, United States
Red Oak Psychiatry Associates, PA
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Houston, Texas, United States
Axiom Research, LLC
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Colton, California, United States
Pharmacology Research Institute
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Newport Beach, California, United States
FutureSearch Trials of Dallas, LP
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Dallas, Texas, United States
Summit Research Network (Oregon) Inc.
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Portland, Oregon, United States
Desert Valley Research
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Rancho Mirage, California, United States
NRC Research Institute
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Orange, California, United States
Atemis Institute for Clinical Research
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San Marcos, California, United States
Midwest Clinical Research Center
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Dayton, Ohio, United States
Heartland Research Associates, LLC
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Wichita, Kansas, United States
Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
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Salem, Oregon, United States
InSite Clinical Research
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DeSoto, Texas, United States
IPS Research Company
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Oklahoma City, Oklahoma, United States
BTC of New Bedford
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New Bedford, Massachusetts, United States
Synergy San Diego
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Lemon Grove, California, United States
Woodland International Research Group
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Little Rock, Arkansas, United States
Comprehensive Psychiatric Care
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Norwich, Connecticut, United States
Meridien Research
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Bradenton, Florida, United States
Clinical Neuroscience Solutions, Inc
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Memphis, Tennessee, United States
Northwest Behavioral Research Center
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Marietta, Georgia, United States
New Hope Clinical Research
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Charlotte, North Carolina, United States
Center for Emotional Fitness
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Cherry Hill, New Jersey, United States
SPRI Clinical Trials, LLC
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Brooklyn, New York, United States
Richmond Behavioral Associates
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Staten Island, New York, United States
Volunteer Research Group, an AMR Company
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Knoxville, Tennessee, United States
Grayline Clinical Drug Trials
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Wichita Falls, Texas, United States
Stedman Clinical Trials
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Tampa, Florida, United States
Child Study Center at Yale University School of Medicine
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New Haven, Connecticut, United States
Albuquerque Neuroscience Inc.
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Albuquerque, New Mexico, United States