Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: Results from a randomized placebo-controlled clinical trial

Trisha Suppes; Suresh Durgam; Susan G Kozauer; Richard Chen; Hassan D Lakkis; Robert E Davis; Andrew Satlin; Kimberly E Vanover; Sharon Mates; Roger S McIntyre; Mauricio Tohen

doi:10.1111/bdi.13310

Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: Results from a randomized placebo-controlled clinical trial

Bipolar Disord. 2023 Sep;25(6):478-488. doi: 10.1111/bdi.13310. Epub 2023 Feb 26.

Authors

Trisha Suppes^{1

2}, Suresh Durgam³, Susan G Kozauer³, Richard Chen³, Hassan D Lakkis³, Robert E Davis³, Andrew Satlin³, Kimberly E Vanover³, Sharon Mates³, Roger S McIntyre^{4

5

6

7}, Mauricio Tohen⁸

Affiliations

¹ Stanford University School of Medicine, Stanford, California, USA.
² US Department of Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.
³ Intra-Cellular Therapies, Inc, New York City, New York, USA.
⁴ Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, Ontario, Canada.
⁵ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

PMID: 36779257
DOI: 10.1111/bdi.13310

Abstract

Objective: This phase 3, randomized, double-blind, placebo-controlled study (NCT02600507) evaluated the efficacy and safety of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression.

Methods: Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (MDE), with inadequate therapeutic response to lithium or valproate, were randomized 1:1:1 to 6 weeks adjunctive therapy with lumateperone 28 mg (n = 176), lumateperone 42 mg (n = 177), or placebo (n = 176). The primary and key secondary efficacy endpoints were change from baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score and the Clinical Global Impression Scale-Bipolar Version-Severity Scale (CGI-BP-S) depression subscore. Safety assessments included adverse events, laboratory evaluations, vital signs, extrapyramidal symptoms (EPS), and suicidality.

Results: Patients treated with adjunctive lumateperone 42 mg showed significantly greater improvement compared with adjunctive placebo in MADRS Total score (LS mean difference vs placebo [LSMD], -2.4; p = 0.02) and CGI-BP-S depression subscore (LSMD, -0.3; p = 0.01), while adjunctive lumateperone 28 mg showed numerical improvement in MADRS Total score (LSMD, -1.7; p = 0.10) and improvement in the CGI-BP-S depression subscore (LSMD, -0.3; p = 0.04). Adjunctive lumateperone treatment was well tolerated; treatment-emergent adverse events reported at rates >5% and twice placebo for lumateperone 42 mg were somnolence (11.3%), dizziness (10.7%), and nausea (8.5%), with minimal risk of EPS, metabolic abnormalities, or increased prolactin.

Conclusions: Lumateperone 42-mg treatment adjunctive to lithium or valproate significantly improved depression symptoms and was generally well tolerated in patients with MDEs associated with either bipolar I or bipolar II disorder.

Keywords: antipsychotic agent; bipolar depression; bipolar disorder; lumateperone.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Antipsychotic Agents*
Bipolar Disorder* / chemically induced
Bipolar Disorder* / drug therapy
Depressive Disorder, Major* / drug therapy
Double-Blind Method
Drug Therapy, Combination
Humans
Lithium / therapeutic use
Treatment Outcome
Valproic Acid / therapeutic use

Substances

lumateperone
Valproic Acid
Lithium
Antipsychotic Agents

Associated data

ClinicalTrials.gov/NCT02600507