Cognitive Effects of MIN-101 in Patients With Schizophrenia and Negative Symptoms: Results From a Randomized Controlled Trial

J Clin Psychiatry. 2018 May/Jun;79(3):17m11753. doi: 10.4088/JCP.17m11753.

Abstract

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, double-blind, 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.

Trial registration: EU Clinical Trials Register identifier: 2014-004878-42​.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Double-Blind Method
  • Female
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Male
  • Middle Aged
  • Narcotic Antagonists / administration & dosage
  • Narcotic Antagonists / pharmacology*
  • Outcome Assessment, Health Care*
  • Prospective Studies
  • Receptors, sigma / antagonists & inhibitors*
  • Schizophrenia / complications
  • Schizophrenia / physiopathology*
  • Serotonin 5-HT2 Receptor Antagonists / administration & dosage
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology*
  • Young Adult

Substances

  • Indoles
  • Narcotic Antagonists
  • Receptors, sigma
  • Serotonin 5-HT2 Receptor Antagonists
  • roluperidone

Associated data

  • EudraCT/2014-004878-42