Long-Term Lumateperone Treatment in Bipolar Disorder: Six-Month Open-label Extension Study

Abstract: Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. A recent Phase 3 trial, Study 401 (NCT02600494) investigating the efficacy and safety of lumateperone 42mg in bipolar depression comprised a 6-week, randomized, double-blind, placebo-controlled period and a 6-month open-label extension period (OLE). Here, we report the results of the OLE, examining long-term safety. Methods: Patients (18-75 years) with a clinical diagnosis of bipolar I or bipolar II disorder experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale Total score≥20 and a Clinical Global Impression Scale-Bipolar Version-Severity score≥4) were eligible for Study 401. Patients completing the double-blind study were eligible for direct rollover into the OLE or were re-screened if completing the double-blind period prior to OLE initiation. During the OLE, lumateperone 42mg was administered once-daily in the evening for 25 weeks. Safety and tolerability were measured by adverse events (AEs), laboratory parameters, cardiometabolic measurements, electrocardiogram (ECG), and vital signs. Results: Of 127 patients enrolled in the OLE, 58.3% (n=74) completed the study. Treatment-emergent AEs (TEAEs) occurred in 73 patients (57.5%) with 54 (42.5%) experiencing a drug-related TEAE. TEAEs that occurred in ≥5% of patients were headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most TEAEs were mild or moderate in severity. Extrapyramidal symptom-related TEAEs were rare. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal. Conclusion: In patients with bipolar depression, long-term lumateperone treatment was generally well tolerated.Short Description: This analysis reports the long-term safety of lumateperone in the open-label extension period (OLE) of a recent Phase 3 trial investigating the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a major depressive episode. In the 25 week OLE, most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. Extrapyramidal-symptom-related TEAEs were rare. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.