Daniel Rutrick1, Dan J Stein2, Ganesan Subramanian3, Brian Smith4, Maurizio Fava5, Gregor Hasler6, Jang-Ho Cha4, Fabrizio Gasparini7, Toni Donchev8, Magdalena Ocwieja7, Donald Johns7,9, Baltazar Gomez-Mancilla10,11. 1. Adams Clinical Trials, Watertown, MA, 02472, USA. 2. MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, 7925, South Africa. 3. Novartis Healthcare Pvt. Ltd., Hyderabad, 500 081, India. 4. Novartis Pharmaceutical Corporation, Cambridge, MA, 02139, USA. 5. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 02115, USA. 6. Division of Molecular Psychiatry, Psychiatric University Hospital, University of Bern, Bern 60, 3000, Bern, Switzerland. 7. Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056, Basel, Switzerland. 8. Clinic of Psychiatry, 1606, Sofia, Bulgaria. 9. Biogen, 300 Binney Street, Cambridge, MA, 02142, USA. 10. Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056, Basel, Switzerland. baltazar.gomezmancilla@novartis.com. 11. Department Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. baltazar.gomezmancilla@novartis.com.
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.
RCT Entities:
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.
Authors: Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Anna L Blobaum; Frank W Byers; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte Journal: Bioorg Med Chem Lett Date: 2018-04-22 Impact factor: 2.823
Authors: Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Katrina A Bollinger; Daryl F Venable; Anna L Blobaum; Frank W Byers; Analisa Thompson Gray; J Scott Daniels; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte Journal: Bioorg Med Chem Lett Date: 2017-09-20 Impact factor: 2.823
Authors: Andrew S Felts; Katrina A Bollinger; Christopher J Brassard; Alice L Rodriguez; Ryan D Morrison; J Scott Daniels; Anna L Blobaum; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Kyle A Emmitte; Craig W Lindsley Journal: Bioorg Med Chem Lett Date: 2018-11-10 Impact factor: 2.823
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Authors: Andrew S Felts; Alice L Rodriguez; Anna L Blobaum; Ryan D Morrison; Brittney S Bates; Analisa Thompson Gray; Jerri M Rook; Mohammed N Tantawy; Frank W Byers; Sichen Chang; Daryl F Venable; Vincent B Luscombe; Gilles D Tamagnan; Colleen M Niswender; J Scott Daniels; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte Journal: J Med Chem Date: 2017-05-31 Impact factor: 7.446
Authors: Anna R Zuena; Luisa Iacovelli; Rosamaria Orlando; Luisa Di Menna; Paola Casolini; Giovanni Sebastiano Alemà; Gabriele Di Cicco; Giuseppe Battaglia; Ferdinando Nicoletti Journal: Front Pharmacol Date: 2018-07-31 Impact factor: 5.810