Abstract
Roluperidone has antagonist properties for 5-HT
, sigma
, α
- and α
-adrenergic receptors, but no dopaminergic binding affinities. In 2 randomized controlled trials (RCT), treatment improved negative symptoms of schizophrenia and social functioning among patients with moderate to severe negative symptoms. We report results of the protocol specified analysis of 2 open-label extension studies of 24 and 40 weeks investigating whether improvement of negative symptoms was sustained without significant adverse effects or worsening of psychosis. Following 12-week double-blind phase of both RCTs, patients were eligible to receive monotherapy roluperidone 32 mg/day or 64 mg/day for 24 weeks (trial 1) or 40 weeks (trial 2) in open-label extension study. Trial 1 included 244 patients of whom 142 entered 24-week open-label extension and trial 2 included 513 patients of whom 341 entered 40-week open-label extension. Trial 1 had PANSS negative factor score of Pentagonal Structure Model as primary outcome. Trial 2 had Marder Negative Symptoms Factor Score as primary outcome measure and Personal and Social Performance (PSP) Total score as secondary outcome. During open-label extensions, continued improvements in negative symptoms and on PSP were observed. Overall rate of symptomatic worsening requiring discontinuation of roluperidone and treatment with an antipsychotic was <10 %. Roluperidone was well tolerated with no meaningful changes in vital signs, laboratory values, weight gain, metabolic indices, or extrapyramidal symptoms. Results of 2 open-label extension trials support roluperidone as a treatment of negative symptoms and social functioning deficits in patients with moderate to severe negative symptoms of schizophrenia.
