TY - JOUR
T1 - Cognitive effects of MIN-101 in patients with schizophrenia and negative symptoms
T2 - Results from a randomized controlled trial
AU - Keefe, Richard S.E.
AU - Harvey, Philip D.
AU - Khan, Anzalee
AU - Saoud, Jay B.
AU - Staner, Corinne
AU - Davidson, Michael
AU - Luthringer, Remy
N1 - Funding Information:
Submitted: June 15, 2017; accepted November 1, 2017. Published online: May 15, 2018. Potential conflicts of interest: Dr Keefe currently or in the past 36 months has received investigator-initiated research funding support from the Department of Veterans Affairs, National Institute of Mental Health, and the Singapore National Medical Research Council; currently or in the past 36 months has received honoraria, served as a consultant, speaker, or advisory board member for Abbvie, Acadia, Aeglea, Akebia, Akili, Alkermes, ArmaGen, Astellas, Avanir, AviNeuro/ChemRar, Axovant, Biogen, Boehringer-Ingelheim, Cerecor, CoMentis, Critical Path Institute, FORUM, Global Medical Education (GME), GW Pharmaceuticals, Intracellular Therapeutics, Janssen, Lundbeck, Lysogene, MedScape, Merck, Minerva Neurosciences, Mitsubishi, Monteris, Moscow Research Institute of Psychiatry, Neuralstem, Neuronix, Novartis, NY State Office of Mental Health, Otsuka, Pfizer, Regenix Bio, Reviva, Roche, Sangamo, Sanofi, Sunovion, Takeda, Targacept, University of Moscow, University of Texas Southwest Medical Center, and WebMD; receives royalties from the BACS testing battery, the MATRICS Battery (BACS Symbol Coding), and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT); and is a shareholder in NeuroCog Trials and Sengenix. Dr Harvey, in the past 36 months, has served as an advisor to Abbvie, Acadia, Allergan, Boehringer-Ingelheim, Forum, Genentech, Lundbeck, Otsuka Digital Health, Sanofi, Sunovion, and Takeda and has received grant support from Takeda. Dr Khan has received funding from National Institute of Mental Health and is an employee at Nathan S. Kline Institute for Psychiatric Research, Manhattan Psychiatric Center, and NeuroCog Trials. Drs Saoud and Staner are employees of PPRS Research. Drs Davidson and Luthringer are employees of Minerva Neurosciences. Funding/support: This study was funded by Minerva Neurosciences Inc. Role of sponsor: Minerva Neurosciences provided funding for the clinical trial. The authors were not paid to generate or review this manuscript.
Publisher Copyright:
© Copyright 2018 Physicians Postgraduate Press, Inc.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Objective: Current dopamine-blocking antipsychotic drugs have little impact on the cognitive deficits associated with schizophrenia. We evaluated whether MIN-101, a molecule that combines sigma-2 antagonism and 5-HT2A antagonism, might improve cognitive deficits in individuals with moderate to severe negative symptoms in schizophrenia. Methods: Individuals (N = 244) aged 18 to 60 years with stable symptoms of DSM-5-defined schizophrenia and moderate to severe negative symptoms were randomized to placebo (n = 83), MIN-101 32 mg (n = 78), or MIN-101 64 mg (n = 83) in a 12-week, phase 2b, prospective, doubleblind, placebo-controlled, parallel-group trial between May 2015 and December 2015. In a post hoc analysis, mean z and T score changes from baseline at 12 weeks of treatment in the cognitive composite score and individual tests on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery were compared between MIN-101 and placebo. Results: A total of 79 patients (95.2%) from the placebo group, 76 (97.4%) from the MIN-101 32 mg group, and 79 (95.2%) from the MIN-101 64 mg group completed the BACS at baseline. The BACS token motor (P = .04), verbal fluency (P = .01), and composite z scores (P = .05) showed significant improvements in the MIN-101 32 mg group compared to the placebo group. At week 4, the clinical improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) negative factor showed a significant correlation with improvements from baseline on the BACS composite in the 64 mg group (r = -0.292, P = .020). At week 12, improvement in the PANSS negative factor showed significant correlations with improvements in the BACS composite (r = -0.408, P = .002), Trail Making Test (r = -0.394, P = .003), and verbal memory (r = -0.322, P = .017) for the 64 mg group. Conclusions: Results suggest a possible benefit of MIN-101 on cognitive performance in individuals with schizophrenia with stable positive symptoms and concurrent clinically significant negative symptoms.
AB - Objective: Current dopamine-blocking antipsychotic drugs have little impact on the cognitive deficits associated with schizophrenia. We evaluated whether MIN-101, a molecule that combines sigma-2 antagonism and 5-HT2A antagonism, might improve cognitive deficits in individuals with moderate to severe negative symptoms in schizophrenia. Methods: Individuals (N = 244) aged 18 to 60 years with stable symptoms of DSM-5-defined schizophrenia and moderate to severe negative symptoms were randomized to placebo (n = 83), MIN-101 32 mg (n = 78), or MIN-101 64 mg (n = 83) in a 12-week, phase 2b, prospective, doubleblind, placebo-controlled, parallel-group trial between May 2015 and December 2015. In a post hoc analysis, mean z and T score changes from baseline at 12 weeks of treatment in the cognitive composite score and individual tests on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery were compared between MIN-101 and placebo. Results: A total of 79 patients (95.2%) from the placebo group, 76 (97.4%) from the MIN-101 32 mg group, and 79 (95.2%) from the MIN-101 64 mg group completed the BACS at baseline. The BACS token motor (P = .04), verbal fluency (P = .01), and composite z scores (P = .05) showed significant improvements in the MIN-101 32 mg group compared to the placebo group. At week 4, the clinical improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) negative factor showed a significant correlation with improvements from baseline on the BACS composite in the 64 mg group (r = -0.292, P = .020). At week 12, improvement in the PANSS negative factor showed significant correlations with improvements in the BACS composite (r = -0.408, P = .002), Trail Making Test (r = -0.394, P = .003), and verbal memory (r = -0.322, P = .017) for the 64 mg group. Conclusions: Results suggest a possible benefit of MIN-101 on cognitive performance in individuals with schizophrenia with stable positive symptoms and concurrent clinically significant negative symptoms.
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U2 - 10.4088/JCP.17m11753
DO - 10.4088/JCP.17m11753
M3 - Article
C2 - 29873956
AN - SCOPUS:85049424221
VL - 79
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
SN - 0160-6689
IS - 3
M1 - 17m11753
ER -