Randomized Trial of Adult Participants With Generalized Anxiety Disorder

A Multicenter, Randomized, Double-Blind, Placebo Controlled Trial of Troriluzole in Generalized Anxiety Disorder

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 881
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • Colton, California, United States, 92324
      • Axiom Research, Llc
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Fresno, California, United States, 93701
      • University of California, San Francisco-Fresno
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC.
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Los Angeles, California, United States, 91423
      • CalNeuro Research Group
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Oakland, California, United States, 94607
      • Pacific Research Partners, LLC
    • Orange, California, United States, 92868
      • NRC Research Institute
    • Rancho Mirage, California, United States, 92270
      • Desert Valley Research
    • San Marcos, California, United States, 92078
      • Atemis Institute for Clinical Research
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc
    • Torrance, California, United States, 90502
      • CNS Network
    • Upland, California, United States, 91786
      • Pacific Clinical Research Medical Group
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Child Study Center at Yale University School of Medicine
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care
  • Florida
    • Bradenton, Florida, United States, 34201
      • Meridien Research
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Hialeah, Florida, United States, 33016
      • Galiz Research
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc
    • North Miami Beach, Florida, United States, 33162
      • Harmony Clinical Research
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta LLC
    • Marietta, Georgia, United States, 30060
      • Northwest Behavioral Research Center
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Phoenix Medical Research
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • New Bedford, Massachusetts, United States, 02740
      • BTC of New Bedford
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research Institute
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center for Emotional Fitness
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience Inc.
  • New York
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials, LLC
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon) Inc.
    • Portland, Oregon, United States, 97214
      • Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates, Inc.
    • Norristown, Pennsylvania, United States, 19403
      • Keystone Clinical Studies, LLC
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group, an AMR Company
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc
  • Texas
    • Dallas, Texas, United States, 91316
      • FutureSearch Trials of Dallas, LP
    • DeSoto, Texas, United States, 75249
      • InSite Clinical Research
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Troriluzole; 100 mg capsule; Other Names: BHV-4157
Placebo Comparator: 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.	Drug: Troriluzole; 100 mg capsule; Other Names: BHV-4157; Drug: Placebo; Placebo matched to troriluzole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the HAM-A Total Score at 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.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	From first dose to Week 8 plus 30 days (maximum duration: 12 weeks)
Number of Participants With Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs Judged to be Related to Study Drug During Extension Phase	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.	From Week 9 to the last dose of troriluzole in extension phase plus 30 days (maximum duration: 333 days)
Number of Participants With Clinically Significant Laboratory Abnormalities During the Randomization Phase	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.	From first dose to Week 8 plus 30 days (maximum duration: 12 weeks)
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at 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).	Baseline, Week 8
Change From Baseline in Clinical Global Impression of Severity Scale (CGI-S) Score at 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.	Baseline, Week 8

Collaborators and Investigators

• Sponsor: Biohaven Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2019
• Primary Completion (Actual): January 14, 2020
• Study Completion (Actual): May 8, 2020

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Generalized Anxiety Disorder (GAD)
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Anxiety Disorders
• Other Study ID Numbers: BHV4157-207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No