(#23) Long-Term Adjunctive Lumateperone Treatment in Major Depressive Disorder: Results From a Six-Month Open-Label Extension Study

Abstract: Background:Lumateperone is FDA-approved to treat schizophrenia and bipolar depression. Adjunctive lumateperone 42mg efficacy and safety was demonstrated in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response (Study 501, NCT04985942; Study 502, NCT05061706). This Phase 3 open-label extension (OLE) Study 503 (NCT05061719) investigated long-term lumateperone 42mg+ADT safety in patients who completed Studies 501/502. Methods:Studies 501/502 enrolled adults with DSM-5ñdefined MDD with inadequate response to 1-2 ADT in the current depressive episode; patients completing 6-week double-blind treatment enrolled in the OLE received 26-week lumateperone 42mg+ADT. Primary endpoint was safety/tolerability. Secondary endpoint was depression by Montgomery-Asberg Depression Rating Scale (MADRS) Total and Clinical Global Impression Scale-Severity (CGI-S) scores. Results:Of 809 patients, 84.5% completed treatment. Treatment-emergent adverse events (TEAEs) occurred in 548 patients (67.7%). Treatment discontinuation due to AEs occurred in 7.4% of patients. TEAEs (?5%) were headache (16.6%), dizziness (10.6%), dry mouth (8.0%), nausea (7.7%), somnolence (7.2%), diarrhea (6.2%), and nasopharyngitis (5.2%). Most TEAEs (98.9%) were mild-to-moderate severity. Extrapyramidal symptom (EPS)-related TEAE rates were low (3.8%) with no mean increase in EPS scales. Changes from baseline to end-of-treatment were minimal and not clinically meaningful for body morphology (weight, body mass index, waist circumference), cardiometabolic parameters, prolactin, blood pressure, and electrocardiogram measures. No emergence of serious suicidal ideation occurred. Depressive symptoms improved, by mean change from Study 501/502 baseline to Week 26 in MADRS Total (?22.9; PShort Description: This Phase 3 open-label extension trial (NCT05061719) investigated long-term 26-week safety of lumateperone 42mg adjunctive to antidepressant therapy (ADT) in patients with major depressive disorder (MDD) with inadequate ADT response. Most common treatment-emergent adverse events were headache, dizziness, dry mouth, nausea, somnolence, diarrhea, and nasopharyngitis. Changes in body morphology and cardiometabolic parameters were minimal. Depressive symptoms improved from baseline to Week 26 with lumateperone+ADT. Overall, lumateperone 42mg+ADT was safe and effective in patients with MDD.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.