(#10) Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From an Additional Randomized, Double-Blind, Phase 3 Trial

Abstract: Background: Lumateperone is FDA-approved to treat schizophrenia and bipolar depression. This Phase 3, randomized, double-blind, placebo-controlled, multicenter trial (NCT05061706) evaluated adjunctive lumateperone 42mg in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response. Methods: Adults with DSM-5ñdiagnosed MDD with inadequate response to 1-2 ADT in the current depressive episode were randomized to 6-week lumateperone 42mg+ADT or placebo+ADT. Primary and key secondary endpoints were change from baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total and Clinical Global Impression Scale-Severity (CGI-S) scores. Additional measures included response (?50% MADRS Total decrease), remission (MADRS Total ?10), and change in Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) Total score. Safety was assessed. Results: Of 480 patients (placebo, 238; lumateperone, 242), 89% completed treatment. Lumateperone+ADT significantly improved MADRS Total (least squares mean difference vs placebo [LSMD]=?4.5; effect size [ES]=?0. 56; PShort Description: This Phase 3, randomized, double-blind, placebo-controlled trial (NCT05061706) evaluated adjunctive lumateperone 42mg in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response. Lumateperone+ADT significantly improved depressive symptoms and disease severity from baseline at Day 43 vs placebo+ADT, meeting primary and key secondary endpoints. Lumateperone+ADT was relatively well-tolerated; adverse events were mostly mild or moderate in severity. These results support lumateperone as a promising adjunctive therapy to treat MDD with inadequate ADT response.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.