Poster
13
(#13) Safety and Tolerability of Lumateperone 42 mg for the Adjunctive Treatment of Major Depressive Disorder: A Pooled Analysis of 2 Randomized Placebo-Controlled Trials
Psych Congress 2025
Abstract: Background: Lumateperone is FDA-approved to treat schizophrenia and bipolar depression. Two Phase 3, randomized, double-blind, placebo-controlled studies (501, NCT04985942; 502, NCT05061706) demonstrated efficacy and safety of lumateperone 42mg + antidepressant therapy (ADT) in patients with major depressive disorder (MDD) with inadequate ADT response. Pooled analysis of these studies evaluated safety and tolerability of lumateperone 42mg+ADT.
Methods: Data were pooled from 2 studies that enrolled adults with DSM-5-defined MDD with inadequate response to 1-2 ADTs in the current depressive episode. Patients had Montgomery-Asberg Depression Rating Scale Total score≥24, Clinical Global Impression Scale-Severity score≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item score≥14. Patients were randomized 1:1 to 6-weeks oral lumateperone 42mg+ADT or placebo+ADT. Safety assessments included adverse events (AEs), vital signs, laboratory parameters, and extrapyramidal symptoms (EPS).
Results: Of 964 patients (placebo, 481; lumateperone, 483), treatment-emergent AEs (TEAEs) occurred in 45.1% of the placebo+ADT and 68.1% of lumateperone+ADT groups. Common TEAEs (≥5%; twice placebo+ADT) were dizziness, dry mouth, somnolence, nausea, and fatigue. Serious TEAEs were rare and unrelated to treatment. Treatment discontinuation due to AEs occurred in 0.8% (placebo) and 8.7% (lumateperone). No patients died during the study. No notable changes from baseline occurred for body morphology (body mass index, waist circumference, and weight), prolactin, metabolic parameters, or EPS scales. Potentially clinically significant (≥7%) weight gain occurred in 1.3% and 0.4% of the placebo+ADT and lumateperone+ADT groups, respectively.
Conclusion: Lumateperone 42mg+ADT was generally safe and well-tolerated in patients MDD with inadequate ADT response, with minimal cardiometabolic, prolactin, and EPS risks.
Short Description: In this pooled analysis of 2 Phase 3 studies (NCT04985942, NCT05061706), safety of lumateperone 42mg + antidepressant therapy (ADT) was assessed in patients with major depressive disorder (MDD) with inadequate ADT response. Common TEAEs included dizziness, dry mouth, somnolence, nausea, and fatigue. Serious TEAEs were rare. Minimal changes occurred in body morphology, cardiometabolic parameters, prolactin, and EPS scales. Lumateperone 42mg+ADT was generally safe and well-tolerated, supporting the use of adjunctive lumateperone for adults with MDD.
Name of Sponsoring Organization(s): Intra-Cellular Therapies, a Johnson & Johnson Company
Methods: Data were pooled from 2 studies that enrolled adults with DSM-5-defined MDD with inadequate response to 1-2 ADTs in the current depressive episode. Patients had Montgomery-Asberg Depression Rating Scale Total score≥24, Clinical Global Impression Scale-Severity score≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item score≥14. Patients were randomized 1:1 to 6-weeks oral lumateperone 42mg+ADT or placebo+ADT. Safety assessments included adverse events (AEs), vital signs, laboratory parameters, and extrapyramidal symptoms (EPS).
Results: Of 964 patients (placebo, 481; lumateperone, 483), treatment-emergent AEs (TEAEs) occurred in 45.1% of the placebo+ADT and 68.1% of lumateperone+ADT groups. Common TEAEs (≥5%; twice placebo+ADT) were dizziness, dry mouth, somnolence, nausea, and fatigue. Serious TEAEs were rare and unrelated to treatment. Treatment discontinuation due to AEs occurred in 0.8% (placebo) and 8.7% (lumateperone). No patients died during the study. No notable changes from baseline occurred for body morphology (body mass index, waist circumference, and weight), prolactin, metabolic parameters, or EPS scales. Potentially clinically significant (≥7%) weight gain occurred in 1.3% and 0.4% of the placebo+ADT and lumateperone+ADT groups, respectively.
Conclusion: Lumateperone 42mg+ADT was generally safe and well-tolerated in patients MDD with inadequate ADT response, with minimal cardiometabolic, prolactin, and EPS risks.
Short Description: In this pooled analysis of 2 Phase 3 studies (NCT04985942, NCT05061706), safety of lumateperone 42mg + antidepressant therapy (ADT) was assessed in patients with major depressive disorder (MDD) with inadequate ADT response. Common TEAEs included dizziness, dry mouth, somnolence, nausea, and fatigue. Serious TEAEs were rare. Minimal changes occurred in body morphology, cardiometabolic parameters, prolactin, and EPS scales. Lumateperone 42mg+ADT was generally safe and well-tolerated, supporting the use of adjunctive lumateperone for adults with MDD.
Name of Sponsoring Organization(s): Intra-Cellular Therapies, a Johnson & Johnson Company
