Metabolic Syndrome in Bipolar Depression With Lumateperone (ITI-007): A Post Hoc Analysis of 2 Randomized, Placebo-Controlled Trials

Abstract: Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. This post hoc, pooled analysis of 2 randomized, double-blind, placebo-controlled studies (Study 401 [NCT02600494]; Study 404 [NCT03249376]) compares rates of metabolic syndrome (MetSy) with lumateperone 42mg monotherapy and placebo in the treatment of bipolar depression. Methods: The incidence and shift in MetSy were analyzed in data pooled from 2 studies that recruited patients (18-75 years) with a diagnosis of bipolar I or bipolar II disorder experiencing an MDE (Montgomery-Åsberg Depression Rating Scale Total score≥20, Clinical Global Impression Scale-Bipolar Version-Severity score≥4). Patients were randomized 1:1 to 6 weeks lumateperone or placebo. Results: The safety population comprised 746 patients (lumateperone=372; placebo=374). Rates of MetSy were similar between groups at baseline (lumateperone, 20.7%; placebo, 22.2%) and the end of treatment (EOT, lumateperone, 21.8%; placebo, 23.8%). More lumateperone patients (36.4%) compared with placebo patients (30.1%) improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. The individual criteria that shifted the most from meeting MetSy criteria at baseline to no longer meeting criteria at EOT was blood pressure for lumateperone (46.8%) and glucose for placebo (43.2%). The rate of MetSy developed during treatment was similar for lumateperone (10.8%) and placebo (10.7%) with approximately half of these patients (lumateperone=43.8%; placebo=45.2%) shifting due to a change in ≥2 criteria. Conclusion: In this post hoc analysis, lumateperone 42mg had a favorable metabolic profile, with similar rates of MetSy compared with placebo.Short Description: A post hoc, pooled analysis of 2 randomized, double-blind, placebo-controlled studies compared rates of metabolic syndrome (MetSy) with lumateperone 42mg vs placebo in patients with a major depressive episode associated with bipolar I or II disorder. At baseline and end of treatment, rates of MetSy were similar between the lumateperone and placebo groups. Compared with placebo, more lumateperone patients improved from having MetSy at baseline to no longer meeting MetSy criteria at end of treatment.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.