Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia

Background This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma(2), and alpha(1A)-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population. Methods Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms. The primary endpoint was the PANSS-derived Negative Symptom Factor Score (NSFS) and the key secondary endpoint was Personal and Social Performance scale (PSP) total score. Results NSFS scores were lower (improved) for roluperidone 64 mg compared to placebo and marginally missing statistical significance for the intent-to-treat (ITT) analysis data set (P <= .064), but reached nominal significance (P <= .044) for the modified-ITT (m-ITT) data set. Changes in PSP total score were statistically significantly better on roluperidone 64 mg compared to placebo for both ITT and m-ITT (P <= .021 and P <= .017, respectively). Conclusions Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning in patients with schizophrenia. Study registration: Eudra-CT: 2017-003333-29; NCT03397134.