PMID- 28044255
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20221207
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Linking)
VI  - 34
IP  - 2
DP  - 2017 Feb
TI  - Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin 
      Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 
      Study.
PG  - 524-541
LID - 10.1007/s12325-016-0468-5 [doi]
AB  - 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.
FAU - Rutrick, Daniel
AU  - Rutrick D
AD  - Adams Clinical Trials, Watertown, MA, 02472, USA.
FAU - Stein, Dan J
AU  - Stein DJ
AD  - MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Groote Schuur 
      Hospital, University of Cape Town, Cape Town, 7925, South Africa.
FAU - Subramanian, Ganesan
AU  - Subramanian G
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, 500 081, India.
FAU - Smith, Brian
AU  - Smith B
AD  - Novartis Pharmaceutical Corporation, Cambridge, MA, 02139, USA.
FAU - Fava, Maurizio
AU  - Fava M
AD  - Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 02115, USA.
FAU - Hasler, Gregor
AU  - Hasler G
AD  - Division of Molecular Psychiatry, Psychiatric University Hospital, University of 
      Bern, Bern 60, 3000, Bern, Switzerland.
FAU - Cha, Jang-Ho
AU  - Cha JH
AD  - Novartis Pharmaceutical Corporation, Cambridge, MA, 02139, USA.
FAU - Gasparini, Fabrizio
AU  - Gasparini F
AD  - Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056, Basel, 
      Switzerland.
FAU - Donchev, Toni
AU  - Donchev T
AD  - Clinic of Psychiatry, 1606, Sofia, Bulgaria.
FAU - Ocwieja, Magdalena
AU  - Ocwieja M
AD  - Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056, Basel, 
      Switzerland.
FAU - Johns, Donald
AU  - Johns D
AD  - Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056, Basel, 
      Switzerland.
AD  - Biogen, 300 Binney Street, Cambridge, MA, 02142, USA.
FAU - Gomez-Mancilla, Baltazar
AU  - Gomez-Mancilla B
AD  - Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056, Basel, 
      Switzerland. baltazar.gomezmancilla@novartis.com.
AD  - Department Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. 
      baltazar.gomezmancilla@novartis.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01813019
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20170102
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Indoles)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - GT0I9SV4F6 (mavoglurant)
MH  - Adult
MH  - Delayed-Action Preparations/administration & dosage/adverse effects
MH  - Diagnostic and Statistical Manual of Mental Disorders
MH  - Double-Blind Method
MH  - Drug Resistance
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Early Termination of Clinical Trials
MH  - Female
MH  - Humans
MH  - *Indoles/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - *Obsessive-Compulsive Disorder/diagnosis/drug therapy
MH  - Psychiatric Status Rating Scales
MH  - Psychotropic Drugs/administration & dosage/adverse effects
MH  - Receptor, Metabotropic Glutamate 5/*antagonists & inhibitors
MH  - Selective Serotonin Reuptake Inhibitors/administration & dosage/adverse effects
MH  - Treatment Outcome
OTO - NOTNLM
OT  - AFQ056
OT  - Glutamate
OT  - Mavoglurant
OT  - Obsessive-compulsive disorder
OT  - Psychiatry
OT  - Randomized controlled trial
OT  - Selective serotonin reuptake inhibitors
EDAT- 2017/01/04 06:00
MHDA- 2017/08/15 06:00
CRDT- 2017/01/04 06:00
PHST- 2016/06/02 00:00 [received]
PHST- 2017/01/04 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2017/01/04 06:00 [entrez]
AID - 10.1007/s12325-016-0468-5 [pii]
AID - 10.1007/s12325-016-0468-5 [doi]
PST - ppublish
SO  - Adv Ther. 2017 Feb;34(2):524-541. doi: 10.1007/s12325-016-0468-5. Epub 2017 Jan 
      2.