Joseph R Calabrese1, Suresh Durgam1, Andrew Satlin1, Kimberly E Vanover1, Robert E Davis1, Richard Chen1, Susan G Kozauer1, Sharon Mates1, Gary S Sachs1. 1. Department of Psychiatry, Case Western Reserve School of Medicine, Cleveland, and University Hospitals Cleveland Medical Center, Cleveland (Calabrese); Intra-Cellular Therapies, Inc., New York (Durgam, Satlin [formerly], Vanover [formerly], Davis, Chen, Kozauer, Mates); Massachusetts General Hospital, Boston, and Signant Health, Plymouth Meeting, Pa. (Sachs).
Abstract
OBJECTIVE: In a phase 3 randomized double-blind placebo-controlled study, the authors investigated the efficacy and safety of 42 mg/day of lumateperone in patients with bipolar I or bipolar II disorder experiencing a major depressive episode. METHODS: Patients 18-75 years old with a clinical diagnosis of bipolar I or bipolar II disorder and experiencing a major depressive episode were eligible for the study. Patients were randomized in a 1:1 ratio to receive 42 mg/day of lumateperone (N=188) or placebo (N=189), administered orally once daily in the evening for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to day 43 in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale-Bipolar Version severity scale (CGI-BP-S), respectively. Safety assessments included treatment-emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms, and suicidality. RESULTS: At day 43, lumateperone treatment was associated with significantly greater improvement from baseline in MADRS score compared with placebo (least squares mean difference compared with placebo, -4.6 points; effect size=-0.56) and CGI-BP-S total score (least squares mean difference compared with placebo, -0.9; effect size=-0.46). Significant MADRS superiority for lumateperone over placebo was observed both in patients with bipolar I and bipolar II disorders. Somnolence and nausea were the only treatment-emergent adverse events that occurred with lumateperone at a clinically meaningful greater rate than placebo. The incidence of extrapyramidal symptom-related treatment-emergent adverse events was low and similar to that for placebo. Minimal changes were observed in weight, vital signs, or metabolic or endocrine assessments. CONCLUSIONS: Lumateperone at 42 mg/day significantly improved depression symptoms and was generally well tolerated in patients with major depressive episodes associated with both bipolar I and bipolar II disorders.
OBJECTIVE: In a phase 3 randomized double-blind placebo-controlled study, the authors investigated the efficacy and safety of 42 mg/day of lumateperone in patients with bipolar I or bipolar II disorder experiencing a major depressive episode. METHODS: Patients 18-75 years old with a clinical diagnosis of bipolar I or bipolar II disorder and experiencing a major depressive episode were eligible for the study. Patients were randomized in a 1:1 ratio to receive 42 mg/day of lumateperone (N=188) or placebo (N=189), administered orally once daily in the evening for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to day 43 in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale-Bipolar Version severity scale (CGI-BP-S), respectively. Safety assessments included treatment-emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms, and suicidality. RESULTS: At day 43, lumateperone treatment was associated with significantly greater improvement from baseline in MADRS score compared with placebo (least squares mean difference compared with placebo, -4.6 points; effect size=-0.56) and CGI-BP-S total score (least squares mean difference compared with placebo, -0.9; effect size=-0.46). Significant MADRS superiority for lumateperone over placebo was observed both in patients with bipolar I and bipolar II disorders. Somnolence and nausea were the only treatment-emergent adverse events that occurred with lumateperone at a clinically meaningful greater rate than placebo. The incidence of extrapyramidal symptom-related treatment-emergent adverse events was low and similar to that for placebo. Minimal changes were observed in weight, vital signs, or metabolic or endocrine assessments. CONCLUSIONS: Lumateperone at 42 mg/day significantly improved depression symptoms and was generally well tolerated in patients with major depressive episodes associated with both bipolar I and bipolar II disorders.
Entities:
Keywords:
Antipsychotics; Bipolar II Disorder; Bipolar and Related Disorders; Clinical Drug Studies
Authors: Roger S McIntyre; Martin Alda; Ross J Baldessarini; Michael Bauer; Michael Berk; Christoph U Correll; Andrea Fagiolini; Kostas Fountoulakis; Mark A Frye; Heinz Grunze; Lars V Kessing; David J Miklowitz; Gordon Parker; Robert M Post; Alan C Swann; Trisha Suppes; Eduard Vieta; Allan Young; Mario Maj Journal: World Psychiatry Date: 2022-10 Impact factor: 79.683
Authors: Melvin G McInnis; Ole A Andreassen; Ana C Andreazza; Uri Alon; Michael Berk; Teri Brister; Katherine E Burdick; Donghong Cui; Mark Frye; Marion Leboyer; Philip B Mitchell; Kathleen Merikangas; Andrew A Nierenberg; John I Nurnberger; Daniel Pham; Eduard Vieta; Lakshmi N Yatham; Allan H Young Journal: Bipolar Disord Date: 2022-03-18 Impact factor: 5.345