Clinical trial NCT01674361: A Study of Bitopertin (RO4917838) in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs) in Participants With Obsessive-Compulsive Disorder (OCD)
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate Efficacy and Safety of RO4917838 in Combination With Selective Serotonin Reuptake Inhibitors in Patients With Obsessive Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-08-28
Enrollment: 99
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: This multicenter, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of bitopertin in combination with SSRI in participants with obsessive-compulsive disorder. Participants will be randomized to receive either bitopertin 30 milligrams (mg) or bitopertin 10 mg or placebo orally daily in addition to their background therapy with an SSRI. Participants will be allocated to one of two strata. Participants in Stratum 1 will start study drug on Day 1. Participants in Stratum 2 will receive placebo from Day 1 (placebo lead-in) and will then start study drug at the Week 2 visit. Participants in both strata will receive the study drug in addition to their background therapy with an SSRI until Week 16.


Eligibility criteria: Inclusion Criteria:

* Primary diagnosis of OCD as per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
* On a stable dose of SSRI for at least 8 weeks prior to screening an between screening and Day 1
* An insufficient response to current treatment with an SSRI given at an adequate dose for at least 12 weeks prior to Day 1
* Females who are not postmenopausal or surgically sterile and who have (or may have) male sexual partners must agree to use two adequate methods of contraception as defined by protocol from the start of screening until 90 days after the last dose of study drug

Exclusion Criteria:

* Primary OCD symptom of hoarding
* More than two unsatisfactory trials within the last 2 years with different serotonin reuptake inhibitors (not including the current treatment with an SSRI) given in an adequate dose for at least 12 weeks
* Failure of more than three augmentation therapies within the last 2 years
* Undergoing acute behavioral therapy or having acute behavioral therapy that was completed less than 4 weeks prior to Day 1
* Any primary DSM-IV-TR Axis I disorder other than OCD
* Current or prior history of bipolar disorder, schizophrenia or other psychotic disorders, schizoaffective disorder, autism or autistic spectrum disorders, borderline personality disorder, or Gilles de la Tourette syndrome if symptoms have persisted into adulthood
* Any eating disorder within the last 6 months
* History of DSM-IV-TR-defined substance dependence and/or substance abuse in the last 6 months, with the exception of nicotine
* Previous treatment with bitopertin or another Glycine transporter 1 inhibitor
* Positive urine drug screening for cannabis, amphetamines (including 3,4-methylenedioxymethamphetamine \[MDMA\]/ecstasy), cocaine, barbiturate, and/or opiates
* Prior or current general medical condition that may impair cognition or other neuropsychiatric functioning
* Body mass index less than (\<) 18.5 kilogram per square meter (kg/m\^2) or greater than (\>) 40 kg/m\^2
* Pregnant or lactating women

Primary outcomes:
measure: Change From Baseline in Total Score on Yale-Brown Obsessive Compulsive Scale (Y-BOCS) After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1), Week 12; Stratum 2: Baseline (Week 2), Week 14
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1), Week 12; Stratum 2: Baseline (Week 2), Week 14
measure: Percentage of Participants with Response as per Pre-defined Criteria Based on the Y-BOCS and CGI
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Change From Baseline in Global Social Functioning Using Sheehan Disability Scale (SDS) Total Score After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1), Week 12; Stratum 2: Baseline (Week 2), Week 14
measure: Change From Baseline in Global Social Functioning Using SDS Domain Scores After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Change From Baseline in Obsessive Compulsive Inventory-Revised (OCI-R) Score After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Change From Baseline in Columbia Suicide Severity Rating Scale After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Mental Component Summary After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Change From Baseline in SF-36 - Physical Component Summary After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Change From Baseline in SF-36 - Domain Scores After 12 Weeks of Treatment
timeFrame: Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14
measure: Area Under The Concentration-Time Curve of Bitopertin
timeFrame: Pre-dose (0 hour) on Day 56 (Week 8), Day 84 (Week 12), Day 98 (Week 14), Day 112 (Week 16); 3 and 6 hours post-dose on Day 112 (Week 16)
Other outcomes:
Locations:
city: Oceanside
country: United States
facility: Excell Research
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine; Neuroscience Research Training Program
state: Connecticut
city: Leesburg
country: United States
facility: Compass Research North, LLC
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Saint Petersburg
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Chicago
country: United States
facility: Uni of Chicago; Centre For Advanced Medicine
state: Illinois
city: New Orleans
country: United States
facility: Louisiana Research Associates
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital - East
state: Massachusetts
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Minneapolis
country: United States
facility: Ambulatory Research Center (ARC), Department of Psychiatry
state: Minnesota
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Saint Louis
country: United States
facility: St Louis Clinical Trials
state: Missouri
city: New York
country: United States
facility: Mount Sinai School of Medicine; Department of Psychiatry
state: New York
city: New York
country: United States
facility: Medical Research Network - New York
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Middleburg Heights
country: United States
facility: North Star Research
state: Ohio
city: Oklahoma City
country: United States
facility: Ips Research Company
state: Oklahoma
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Providence
country: United States
facility: Butler Hospital - Department of Psychiatry and Human Behavior
state: Rhode Island
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions,Inc
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials, LP
state: Texas
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Middleton
country: United States
facility: Dean Foundation
state: Wisconsin
city: Edmonton
country: Canada
facility: Chokka Center for Integrative Health
state: Alberta
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research-Halifax
state: Nova Scotia
city: Kentville
country: Canada
facility: True North Clinical Research Kentville
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University - MacAnxiety Research Centre
state: Ontario
city: Mississauga
country: Canada
facility: Sunny Johnson Medical Research Associates Inc.; Medical Research Associates
state: Ontario
city: Toronto
country: Canada
facility: START Clinic for Mood & Anxiety Disorders
state: Ontario
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bandeira ID, Lins-Silva DH, Cavenaghi VB, Dorea-Bandeira I, Faria-Guimaraes D, Barouh JL, Jesus-Nunes AP, Beanes G, Souza LS, Leal GC, Sanacora G, Miguel EC, Sampaio AS, Quarantini LC. Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review. Harv Rev Psychiatry. 2022 Mar-Apr 01;30(2):135-145. doi: 10.1097/HRP.0000000000000330.