Randomized Trial of Adult Participants With Generalized Anxiety Disorder

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

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

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: Troriluzole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Troriluzole<br>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<br>* 100 mg capsule<br>* Other names: BHV-4157;|
| Placebo Comparator: Placebo<br>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<br>* 100 mg capsule<br>* Other names: BHV-4157;Drug: Placebo<br>* Placebo matched to troriluzole<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Generalized Anxiety Disorder (GAD)