A Study of Bitopertin (RO4917838) in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs) in Participants With Obsessive-Compulsive Disorder (OCD)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Obsessive-Compulsive Disorder

Intervention / Treatment
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* Drug: Bitopertin
* Drug: Placebo
* Drug: SSRI


Participation Criteria
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Eligibility Criteria
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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

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bitopertin 30 mg<br>Participants in Stratum 1 will receive bitopertin 30 mg from Day 1 to Week 16 in addition to their background therapy with an SSRI. Participants in Stratum 2 will receive placebo from Day 1 and will then start bitopertin 30 mg at the Week 2 until Week 16 in addition to their background therapy with an SSRI. | Drug: Bitopertin<br>* Bitopertin once daily orally.<br>* Other names: RO4917838;Drug: Placebo<br>* Placebo matched to bitopertin once daily orally.<br>Drug: SSRI<br>* Participants will continue their background SSRI treatment as per standard of care at the same dose taken during the 8 weeks prior to Day 1. Protocol does not enforce any particular SSRI drug or regimen.<br>|
| Experimental: Bitopertin 10 mg<br>Participants in Stratum 1 will receive bitopertin 10 mg from Day 1 to Week 16 in addition to their background therapy with an SSRI. Participants in Stratum 2 will receive placebo from Day 1 and will then start bitopertin 10 mg at the Week 2 until Week 16 in addition to their background therapy with an SSRI. | Drug: Bitopertin<br>* Bitopertin once daily orally.<br>* Other names: RO4917838;Drug: Placebo<br>* Placebo matched to bitopertin once daily orally.<br>Drug: SSRI<br>* Participants will continue their background SSRI treatment as per standard of care at the same dose taken during the 8 weeks prior to Day 1. Protocol does not enforce any particular SSRI drug or regimen.<br>|
| Placebo Comparator: Placebo<br>Participants (both Stratum 1 and Stratum 2) will receive placebo from Day 1 to Week 16 in addition to their background therapy with an SSRI. | Drug: Placebo<br>* Placebo matched to bitopertin once daily orally.<br>Drug: SSRI<br>* Participants will continue their background SSRI treatment as per standard of care at the same dose taken during the 8 weeks prior to Day 1. Protocol does not enforce any particular SSRI drug or regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Score on Yale-Brown Obsessive Compulsive Scale (Y-BOCS) After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1), Week 12; Stratum 2: Baseline (Week 2), Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1), Week 12; Stratum 2: Baseline (Week 2), Week 14 | 
| Percentage of Participants with Response as per Pre-defined Criteria Based on the Y-BOCS and CGI | Response will be defined as having: At least a 35 percent (%) reduction on the total Y-BOCS score from baseline. A much or very much improved on the Clinical Global Impression of Change (CGI-C) rating from baseline. A combination of at least 35% reduction on the total Y-BOCS score from baseline and much or very much improved on the CGI-C from baseline. Achieved remission, as shown by a total Y-BOCS score less than or equal to (≤)10. | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Change From Baseline in Global Social Functioning Using Sheehan Disability Scale (SDS) Total Score After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1), Week 12; Stratum 2: Baseline (Week 2), Week 14 | 
| Change From Baseline in Global Social Functioning Using SDS Domain Scores After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Change From Baseline in Obsessive Compulsive Inventory-Revised (OCI-R) Score After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Change From Baseline in Columbia Suicide Severity Rating Scale After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Mental Component Summary After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Change From Baseline in SF-36 - Physical Component Summary After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Change From Baseline in SF-36 - Domain Scores After 12 Weeks of Treatment |  | Stratum 1: Baseline (Day 1) up to Week 12; Stratum 2: Baseline (Week 2) up to Week 14 | 
| Area Under The Concentration-Time Curve of Bitopertin |  | 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) |