Efficacy and safety of brexpiprazole in early-episode schizophrenia: post hoc analysis of Phase 3 clinical trials in adults and adolescents

OBJECTIVE: To evaluate the efficacy and safety of brexpiprazole in patients with early-episode schizophrenia. METHODS: Data were pooled from four 6-week, randomized, double-blind, placebo-controlled trials in schizophrenia. Three trials (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380) enrolled adults aged 18-65 years; one trial (NCT03198078) enrolled adolescents aged 13-17 years. Data from participants meeting early-episode criteria (age 13-35 years, ≤5 years illness duration) were pooled for participants randomized to brexpiprazole 2-4 mg or placebo. Efficacy on schizophrenia symptoms was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS; primary endpoint in all trials). Change in functioning was measured using the Personal and Social Performance (PSP) scale in adults and Children's Global Assessment Scale (CGAS) in adolescents. Safety was also assessed. RESULTS: Across 476 participants (brexpiprazole 2-4 mg/day, n = 289; placebo, n = 187), change from baseline to Week 6 was greater with brexpiprazole versus placebo on PANSS total score (least squares LS mean difference -3.6; 95% confidence interval CI -7.0, -0.1; p = 0.04; Cohen's d 0.19), and a combined PSP/CGAS functioning score (LS mean difference 2.3; 95% CI: 0.1, 4.5; p = 0.04; Cohen's d 0.19). The incidence of treatment-emergent adverse events (TEAEs) was 50.7% with brexpiprazole and 46.3% with placebo. The most common TEAEs with brexpiprazole were insomnia (brexpiprazole, 9.2%; placebo, 9.5%) and akathisia (brexpiprazole, 6.5%; placebo, 2.1%). CONCLUSION: This analysis expands the evidence base for brexpiprazole in schizophrenia by demonstrating efficacy in patients who are early in their disease course. The safety profile of brexpiprazole was consistent with previous clinical trials.