Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 Study

Adv Ther. 2017 Feb;34(2):524-541. doi: 10.1007/s12325-016-0468-5. Epub 2017 Jan 2.

Abstract

Introduction: To determine if mavoglurant (modified release) as an augmentation therapy to selective serotonin reuptake inhibitors (SSRIs) could have beneficial effects reducing Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score in patients with obsessive-compulsive disorder (OCD) resistant to SSRI treatment.

Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2 study. Patients remained on their SSRI treatment and mavoglurant or placebo was added on. Non-smoking men and women aged 18-65 years primarily diagnosed with OCD according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria were randomized (1:1) to mavoglurant or placebo groups. After 50 patients were randomized, an interim analysis was conducted to determine whether the study should be continued. The primary outcome measure was absolute change in Y-BOCS from baseline at week 17. Safety was assessed by recording adverse events (AEs) and serious adverse events (SAEs).

Results: Interim analysis led to a decision to terminate the study. In total 38 (76.0%) participants completed 17 weeks of treatment and 37 (74.0%) completed the study. There was no significant difference in least squares (LS) mean change from baseline at week 17 in Y-BOCS total score for mavoglurant compared with placebo groups [-6.9 (1.75) vs. -8.0 (1.78), respectively; LS mean difference 1.1; 95% CI -3.9, 6.2; p = 0.671]. The incidence of AEs was higher in the mavoglurant compared with the placebo group (80.8% vs. 70.8%, respectively).

Conclusion: This study of mavoglurant in OCD was terminated because of the lack of efficacy at interim analysis. The study did not support the use of an antagonist of mGluR5 receptors for OCD treatment.

Trial registration: The study was registered with ClinicalTrials.gov: NCT01813019.

Funding: This study was sponsored by Novartis Pharma AG, Basel, Switzerland.

Keywords: AFQ056; Glutamate; Mavoglurant; Obsessive–compulsive disorder; Psychiatry; Randomized controlled trial; Selective serotonin reuptake inhibitors.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Diagnostic and Statistical Manual of Mental Disorders
  • Double-Blind Method
  • Drug Resistance
  • Drug Synergism
  • Drug Therapy, Combination
  • Early Termination of Clinical Trials
  • Female
  • Humans
  • Indoles* / administration & dosage
  • Indoles* / adverse effects
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder* / diagnosis
  • Obsessive-Compulsive Disorder* / drug therapy
  • Psychiatric Status Rating Scales
  • Psychotropic Drugs / administration & dosage
  • Psychotropic Drugs / adverse effects
  • Receptor, Metabotropic Glutamate 5 / antagonists & inhibitors*
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Indoles
  • Psychotropic Drugs
  • Receptor, Metabotropic Glutamate 5
  • Serotonin Uptake Inhibitors
  • mavoglurant

Associated data

  • ClinicalTrials.gov/NCT01813019