Long-term safety and tolerability of lumateperone 42 mg in patients with bipolar disorder: results from a 6-month open-label extension study.

This 6-month open-label extension (OLE) period of a Phase 3 placebo-controlled study (NCT02600494) examined the safety of lumateperone in patients with bipolar I or bipolar II depression. Eligible patients completing the placebo-controlled period received lumateperone 42 mg once daily up to 175 days. The primary endpoint was safety and tolerability, assessed by adverse events (AEs) and clinical laboratory evaluations analyzed by imputing missing data using a last observation carried forward approach. The secondary endpoint was efficacy measured by Montgomery-Åsberg Depression Rating Scale (MADRS) total and Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) scores. Of 127 patients in the OLE, 58.3% completed treatment, and 42.5% experienced a drug-related treatment-emergent AE (TEAE); the most common TEAEs were headache (20.5%), dry mouth (11.8%), dizziness (10.2%), and nausea (10.2%). The majority (92%) of TEAEs were of mild or moderate severity. There were no notable changes in extrapyramidal symptom scores, cardiometabolic parameters, or body morphology. MADRS total score (mean change, -8.9, nominal P < 0.0001), CGI-BP-S total score (-2.3, nominal P < 0.0001), and CGI-BP-S depression subscore (-1.3, nominal P < 0.0001) improved over time, from baseline to Day 175. Overall, 6-month lumateperone 42 mg was generally well tolerated, and depressive symptoms based on MADRS total score and CGI-BP-S improved over time.