Efficacy and Safety of Brexpiprazole for the Treatment of Borderline Personality Disorder: a 12-Week, Phase 2, Randomized, Double-Blind, Placebo-Controlled Study

Abstract: Background: Atypical antipsychotics may be efficacious in the treatment of borderline personality disorder (BPD). This double-blind, Phase 2 study (NCT04100096) evaluated the efficacy and safety of brexpiprazole in BPD treatment. Methods: Following a 1-week placebo run-in phase, adults with BPD were randomized (1:1) to brexpiprazole 2–3 mg/day (n=159) or placebo (n=165) for 11 weeks. The primary endpoint was the change in Zanarini Rating Scale for BPD (ZAN-BPD) Total score from randomization to Week 10. The key secondary endpoint was the change in Clinical Global Impression – Severity (CGI-S) score from randomization to Week 10. Safety was assessed by standard variables. Results: Mean ZAN-BPD Total and CGI-S scores at baseline indicated moderate severity of BPD in both groups. Study completion rate was 73.8% (placebo: 77.0%; brexpiprazole: 70.4%). No statistically significant difference was observed between brexpiprazole and placebo in mean change from randomization to Week 10 in ZAN-BPD Total score (placebo: -6.25; brexpiprazole: -7.27; p=0.24) and in CGI-S score (placebo: -1.09; brexpiprazole: -1.13; p=0.78). However, brexpiprazole was associated with nominally significant improvements versus placebo in ZAN-BPD Total score at Week 8 (p=0.029) and Week 12 (p=0.010), and in CGI-S score at Week 12 (p=0.031). The incidence of treatment-emergent adverse events was 60.5% with brexpiprazole and 47.9% with placebo. Conclusion: There was no statistically significant difference between brexpiprazole and placebo efficacy in the primary and secondary endpoints, although exploratory analyses favored brexpiprazole at other timepoints. Brexpiprazole was generally well tolerated, with a safety profile similar to that observed in other indications.Short Description: This double-blind study evaluated the efficacy and safety of brexpiprazole 2–3 mg/day in 324 patients with borderline personality disorder (NCT04100096). No statistically significant difference was observed between brexpiprazole and placebo in mean change from randomization to Week 10 in ZAN-BPD Total score (p=0.24) or in CGI-S score (p=0.78), although exploratory analyses favored brexpiprazole at other timepoints. Brexpiprazole was generally well tolerated, with a safety profile similar to that of other indications.Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA, and H. Lundbeck A/S, Valby, Denmark