Efficacy of Lumateperone in Pooled Short-Term Late-Phase Clinical Trials for the Treatment of Major Depressive Episodes Associated With Bipolar II Disorder

This work was sponsored by Intra-Cellular Therapies, Inc. Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder as monotherapy and as adjunctive therapy with lithium or valproate. This analysis evaluated the efficacy of lumateperone 42mg across pooled short-term studies in patients with depressive episodes associated with bipolar II disorder. Methods: Trials enrolled adults (18-75 years) with bipolar I or II disorder experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score≥20 and Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score≥4), stratified by bipolar I or bipolar II diagnosis. This post hoc analysis pooled data from 3 placebo-controlled studies of once-daily lumateperone 42mg monotherapy (Study 401 [NCT02600494], Study 404 [NCT03249376]) and adjunctive therapy to lithium/valproate (Study 402 [NCT02600507]). Assessments included change from baseline in MADRS Total score, CGI-BP-S Total score, and CGI-BP-S subscores. Results: Lumateperone 42mg significantly improved MADRS Total score compared with placebo from baseline to Day 43 in the pooled intent-to-treat population (placebo, n=539; lumateperone 42mg, n=528; least squares mean difference vs placebo [LSMD], −2.5; 95% CI −3.8, −1.2; P<.001 and="" in="" the="" patients="" with="" bipolar="" ii="" disorder="" n="87;" lumateperone="" lsmd="" ci="" p="" significantly="" improved="" illness="" severity="" at="" day="" compared="" placebo="" as="" measured="" by="" cgi-bp-s="" total="" depression="" overall="" scores="" conclusion:="" short-term="" monotherapy="" or="" adjunctive="" therapy="" symptoms="" of="" disease="" disorder.="">