Efficacy and safety of brexpiprazole in schizophrenia: Meta-analysis of three double-blind, randomized, placebo-controlled phase 3 studies

Abstract

Introduction

Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.

Objectives

To evaluate the efficacy, safety, and tolerability of brexpiprazole in patients with acute schizophrenia in a meta-analysis of three phase 3 studies with brexpiprazole.

Aim

The primary endpoint was change from baseline to week 6 in PANSS total score.

Methods

Data from the 3 clinical studies in patients with acute schizophrenia were combined and analyzed using individual patient data meta-analysis. In two similarly designed studies (NCT01396421; NCT01393613), patients with acute schizophrenia were randomized to fixed-doses of brexpiprazole 2 mg/day, 4 mg/day or placebo (a low-dose treatment group was included in each study [0.25 mg and 1.0 mg]; not included in the meta-analysis). In the third study (NCT01810380), patients were randomized to flexible dosing of brexpiprazole (2 to 4 mg/day), placebo, or an active reference (quetiapine extended release). Changes from baseline for brexpiprazole vs. placebo were analyzed using an MMRM approach.

Results

Brexpiprazole 2–4 mg (n = 868) was superior to placebo (n = 517) in change from baseline in PANSS total score (−20.1 vs. −14.3; estimated treatment difference to placebo: −5.8 [95% CI: −8.0; −3.6]; P < 0.001). The proportions of patients reporting TEAEs were similar between the brexpiprazole and placebo treatment groups (57.9% vs. 57.5%). No unexpected safety concerns were observed.

Conclusion

This meta-analysis supports evidence from three individual trials that brexpiprazole is efficacious and safe in treating patients with acute schizophrenia.

Disclosure of interest

The authors have not supplied their declaration of competing interest.