(#25) Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder: Results From a 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 (NCT04985942) investigated adjunctive lumateperone 42mg in patients with major depressive disorder (MDD) with inadequate response to antidepressant therapy (ADT). 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 efficacy 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 Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) Total score. Safety was assessed. Results: Of 484 patients treated (placebo, 243; lumateperone, 241), 93% completed treatment. Lumateperone+ADT significantly improved MADRS Total (least squares mean difference vs placebo [LSMD]=?4.9; effect size [ES]=?0.61; PShort Description: This Phase 3, randomized, double-blind, placebo-controlled trial (NCT04985942) investigated adjunctive lumateperone 42mg in patients with major depressive disorder (MDD) with inadequate response to antidepressant therapy (ADT). Lumateperone+ADT met the primary and key secondary endpoints, significantly improving depressive symptoms and disease severity from baseline to Day 43 vs placebo+ADT. Lumateperone+ADT was generally well-tolerated; most common treatment-emergent adverse events were dry mouth, fatigue, and tremor. The results indicate lumateperone as a promising adjunctive therapy to treat MDD.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.