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 monotherapy 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. Implications: Both doses of roluperidone previously improved PANSS negative symptoms in general and demonstrated tolerability in stable schizophrenia patients. The post hoc analysis reported here found the drug to work on both the reduced emotional experience and reduced emotional expression sub-scales empirically derived from the PANSS.