Efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia: Results from a randomized, double-blind, placebo-controlled, multicenter, dose-finding study

Rationale: Bifeprunox is a partial dopamine agonist with a unique receptor-binding profile and potential antipsychotic properties. Objectives: The current study evaluated the efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia. Materials and methods: In this 6-week, double-blind, placebo-controlled study, 589 patients were randomly assigned to once-daily treatment with bifeprunox 5, 10, or 20 mg, placebo, or risperidone 6 mg. Efficacy was assessed by changes in symptom rating scales [Positive and Negative Syndrome Scale (PANSS) total and subscale scores; PANSS-derived BPRS scores; Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores]. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms (EPS), laboratory values, electrocardiograms, prolactin levels, and weight. Results: Compared with placebo, bifeprunox 20 mg produced a statistically significantly greater reduction from baseline to last assessment in the primary efficacy variable (PANSS total score; effect size=-0.339), as well as most secondary efficacy measures. No statistically significant differences in efficacy were seen with lower doses of bifeprunox. The most common treatment-emergent adverse events (TEAEs) noted with bifeprunox were gastrointestinal; no clear dose-related trend in the incidence of any TEAE was observed in the bifeprunox groups. Compared to placebo, treatment with bifeprunox led to small but statistically significant decreases in weight and prolactin levels. EPS were comparable between bifeprunox and placebo. The active reference in this study, risperidone 6 mg, showed statistically significant differences from placebo for the primary efficacy parameter (effect size=-0.628) and all secondary efficacy parameters. Conclusions: These data suggest that 20 mg of bifeprunox may be efficacious in improving symptoms in patients with an acute exacerbation of schizophrenia. Bifeprunox appeared to be safe and well tolerated by patients in this 6-week study.