Efficacy and Safety of BI 1358894 in Patients With Borderline Personality Disorder: Results of a Phase 2 Randomized, Placebo-Controlled, Parallel Group Dose-Ranging Trial

Objective: To provide proof-of-concept (PoC), dose-range finding, and safety data for BI 1358894, a TRPC4/5 ion channel inhibitor, in patients with borderline personality disorder (BPD). Methods: This was a phase 2, multinational, randomized, double-blind, placebo-controlled trial. Patients were randomized to oral placebo or BI 1358894 (5 mg, 25 mg, 75 mg, or 125 mg) once daily in a 2.5:1:1:1:2 ratio for 12 weeks. The primary end point was change from baseline in the Zanarini Rating Scale for BPD (ZAN-BPD) total score at Week 10. Secondary end points included ≥30% ZAN-BPD reduction response from baseline at Week 10, change from baseline at Week 10 in the Difficulties in Emotion Regulation Scale-16 item total, State-Trait Anxiety Inventory–State Anxiety total, Patient Health Questionnaire-9 total, Clinical Global Impressions–Severity, and Patient Global Impression–Severity scores. Results: Of 655 enrolled patients, 390 were randomized and 323 (82.8%) completed the trial. For primary and secondary end points, no differences were observed between treatment and placebo; therefore, PoC was not established. The proportion of patients with adverse events (AEs, BI 1358894 overall vs placebo: 77.9% vs 75.0%) and serious AEs (SAEs; 10.3% vs 8.6%) was comparable between treatments. The proportion of patients with an SAE of suicidal ideation was 4.2% (BI 1358894 overall) and 6.3% (placebo). Conclusions: Although the primary end point was not met, BI 1358894 was well tolerated with no increase in self-harm or suicidality. More targeted populations, alternative outcome assessments, and additional measures to minimize placebo effects should be considered for future trials.