Clinical trial NCT03299166: Troriluzole (BHV-4157) in Adult Participants With Obsessive Compulsive Disorder
Official title: A Randomized, Double-blind, Placebo-controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-02
Enrollment: 426
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of troriluzole as adjunctive therapy versus placebo in participants with obsessive compulsive disorder (OCD) who had an inadequate response to selective serotonin reuptake inhibitor (SSRI), clomipramine, venlafaxine, or desvenlafaxine treatment


Eligibility criteria: Inclusion Criteria:

1. Primary diagnosis of OCD as per the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).
2. Participants must be currently experiencing non-response or inadequate response to their current standard of care (SOC) medication defined as:

   1. Participant Yale-Brown Obsessive Compulsive Scale total score must be ≥ 19 at screening and Baseline, reflecting moderate or severe OCD symptoms.
   2. Participants must currently be on a SSRI, clomipramine, venlafaxine or desvenlafaxine.
3. 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;
4. Minimum of 6 years of education or equivalent and sufficiently fluent in English to complete necessary scales and understand consent forms;
5. Participants must have adequate hearing, vision, and language skills to perform neuropsychiatric testing and interviews as specified in the protocol;
6. 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;
7. It is required that all women of child-bearing potential (WOCBP) who are sexually active agree to use two methods of contraception for the duration of the study (i.e. beginning 30 days prior to baseline and extending to 30 days after the last dose of study drug).
8. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to dosing at Baseline;
9. It is required that men who are sexually active with WOCBP agree to use 2 methods of contraception for the duration of the study (beginning at first treatment and extending to 90 days after the last dose of study drug).
10. The duration of the subject's OCD disease was to be ≥ 1 year.
11. In addition, subjects had to be on stable doses of other psychotropic medication for at least 12 weeks prior to screening.
12. Subjects had to have a Clinical Global Impression of Severity Scale (CGI-S) score of ≥ 4 at screening and baseline.

Exclusion Criteria:

1. Participants should be excluded with a history of more than 2 previous failed treatment trials of SSRIs, clomipramine, venlafaxine, or desvenlafaxine (not including the current SSRI trial) given for an adequate duration at an adequate dose as defined by the following criteria taken from the Massachusetts General Hospital Treatment Response Questionnaire for OCD (MGH-TRQ-OCD) as follows:

   1. Treatment failure / non-response: As per the MGH-TRQ-OCD, there has been minimal or no meaningful clinical benefit as perceived by the participant despite an adequate dose and duration of treatment;
   2. Adequate duration: At least 10 weeks of treatment with SSRI, clomipramine, venlafaxine, or desvenlafaxine
   3. Adequate dose: Defined by the the United States Prescribing Information labeling.
2. Evidence at screening or baseline of any medical or psychiatric condition other than OCD that could predominantly explain or contribute significantly to the subjects' symptoms or that could confound assessment of OCD symptoms
3. Mini Mental State Examination (MMSE) score of \< 24 at Screening
4. Current or prior history, per DSM-5 criteria, of bipolar I or II disorder, schizophrenia or other psychotic disorders, schizoaffective disorder, autism or autistic spectrum disorders, borderline personality disorder, antisocial personality disorder, body dysmorphic disorder, hoarding disorder (symptoms of hoarding disorder as part of the OCD diagnosis are allowed, but a primary diagnosis of hoarding disorder is excluded); a current diagnosis of Tourette's disorder is also excluded;
5. Any eating disorder within the last 12 months;
6. Acute suicidality or suicide attempt or self-injurious behavior in the last 6 months;
7. History of psychosurgery, Deep Brain Stimulation (DBS) or Electroconvulsive Therapy (ECT).
8. Transcranial Magnetic Stimulation (TMS) is prohibited within 3 months prior to screening and during the study.
9. Participants who may have received a non-biological investigational agent in any clinical trial within 30 days, or a biological agent within 90 days prior to screening are excluded.
10. Creatinine ≥ 2 mg/dL.
11. Course of treatment for participants with localized cancers (without metastatic spread) is 5 years prior to screening.
12. QTcF (Fridericia) interval ≥ 470 msec during the screening or baseline period or uncontrolled arrhythmia or frequent premature ventricular contraction (PVCs) (\> 5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block, or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥150 msec or evidence of acute or sub-acute myocardial infarction or ischemia and added or other electrocardiogram findings that, in the investigator's opinion, would preclude participation in the study.
13. Previous treatment with riluzole

Primary outcomes:
measure: Change From Baseline in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Total Score
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) and AEs Leading to Study Drug Discontinuation in the DB Randomization Phase
timeFrame: Up to 12 weeks
measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) and AEs Leading to Study Drug Discontinuation in the Open-Label Extension Phase
timeFrame: Up to 96 weeks
measure: Number of Participants With Clinically Significant Laboratory Abnormalities During the DB Randomization Phase
timeFrame: Up to 12 weeks
measure: Change From Baseline in Functional Disability Assessed Using the Sheehan Disability Scale (SDS) Total Score
timeFrame: Baseline, Week 12
measure: Change From Baseline in Clinical Global Impression of Severity Scale (CGI-S) Score
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Y-BOCS Obsessions Sub-Scale Score
timeFrame: Baseline, Week 12
Other outcomes:
measure: Change From Baseline in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Total Score at Weeks 4 and 8
timeFrame: Baseline, Week 4 and Week 8
Locations:
city: Chandler
country: United States
facility: Metropolitan Neuro Behavioral Institute
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Lemon Grove
country: United States
facility: Synergy Research San Diego
state: California
city: Los Angeles
country: United States
facility: CalNeuro Research Group
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Rancho Mirage
country: United States
facility: Desert Valley Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Marcos
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Stanford
country: United States
facility: Stanford University, Department of Psychiatry and Behavioral Sciences
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Medical Group
state: California
city: Denver
country: United States
facility: Mountain View Clinical Research, Inc.
state: Colorado
city: Hartford
country: United States
facility: Institute of Living / Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Norwich
country: United States
facility: Comprehensive Psychiatric Care
state: Connecticut
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida Department of Psychiatry
state: Florida
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Kissimmee
country: United States
facility: SIH Research, Inc
state: Florida
city: North Miami Beach
country: United States
facility: Harmony Clinical Research
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Savannah
country: United States
facility: iResearch Savannah
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Department of Psychiatry & Behavioral Neuroscience
state: Illinois
city: Naperville
country: United States
facility: AMR-Baber Research, Inc
state: Illinois
city: Prairie Village
country: United States
facility: Phoenix Medical Research, Inc.
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Pikesville
country: United States
facility: Pharmasite Research, Inc.
state: Maryland
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Clinical Research PC
state: Michigan
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Portsmouth
country: United States
facility: ActivMed Practices and Research, Inc.
state: New Hampshire
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Brooklyn
country: United States
facility: Integrative Clinical Trials LLC
state: New York
city: Great Neck
country: United States
facility: Bio Behavioral Institute
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Charlottesville
country: United States
facility: Psychiatric Alliance of the Blue Ridge, Inc.
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
Study officials:
References: