Efficacy and safety of MIN-101: A new drug for the treatment of negative symptoms in schizophrenia a 12-week randomized, double blind, placebo-controlled trial

Abstract

Objective

To compare the efficacy, safety, and tolerability of MIN-101, a compound with high affinities for sigma 2 and 5-HT 2A receptors, to placebo in treating negative symptoms, in stabilized patients with schizophrenia.

Methods

This multi-national phase 2b trial enrolled 244 patients with schizophrenia who were symptomatically stable for ≥ 3 months prior to entering the trial and had scores ≥ 20 negative subscale of the PANSS. Patients were randomized to monotherapy with MIN-101 32 mg/day, MIN-101 64 mg/day or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the five factors (pentagonal) model.

Results

Statistically significant reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (P ≤ 0.022, ES 0.45 and ≤ 0.003, ES 0.58, respectively). This was supported by similar effects on most of the secondary measurements including: the PANSS three factors negative symptoms subscale, PANSS total score, CGI, BACS, CDSS, and PSP. There were no statistically significant differences in PANSS positive subscale scores between MIN-101 and placebo. No weight gain or clinically significant changes in vital sings, prolactin levels, routine laboratory values, metabolic indices and extrapyramidal symptom scores (EPS) were observed.

Conclusions

Since positive symptoms and EPS did not change, the improvement in negative symptoms was not secondary to improvement in positive symptoms or EPS, suggesting that MIN-101 might be the first specific treatment to have a direct effect on negative symptoms.

Disclosure of interest

I have received consultant fees from Minerva Neuroscience the sponsor of this trial and own stock of Minerva Neuroscience