Effects of Roluperidone (MIN-101) on two dimensions of the negative symptoms factor score: Reduced emotional experience and reduced emotional expression.

Background: Recent research has suggested that negative symptoms (NS) can be considered in terms of two different dimensions: reduced expression (expressive deficit) and reduced experience (experiential deficit). Roluperidone, a compound with high affinities for 5 HT2A and sigma2 receptors, has previously shown superiority over placebo on improving NS in a prospective study in patients with schizophrenia. The objective here is to explore the effect of roluperidone compared to placebo, on the 2 domains of the Negative Symptoms. Methods: This was a multi-national Phase 2b trial that enrolled 244 symptomatically stable patients with schizophrenia who had baseline scores >= 20 on the NS subscale of the PANSS. Patients were randomized to daily mono-therapy with roluperidone 32 mg, roluperidone 64 mg, or placebo in a 1:1:1 ratio. All enrolled patients were Caucasian, and 137 (56%) were male. The 3 treatment groups were balanced on all demographic and illness-related baseline characteristics. Results: Both doses of roluperidone were superior to placebo on both domains: Reduced Experience (p <=.006 for the 32 mg; p <=.001 for the 64 mg) with persistent superiority from Week 2 for the 64 mg dose and Week 8 for the 32 mg dose; Reduced Expression (p <=.003 for 32 mg: p <=.001 for 64 mg) with similar persistence. (C) 2019 Elsevier B.V. All rights reserved.