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NCT04285515

Clinical Trial Evaluating Lumateperone Monotherapy in the Treatment of Bipolar Depression or Major Depressive Disorder

Completed Phase 3 Results posted Last updated 19 March 2025
What this trial tests

Phase 3 trial testing Lumateperone in Bipolar Depression in 488 participants. Completed in 30 November 2022.

Timeline
27 February 2020
Primary endpoint
30 November 2022
30 November 2022

Quick facts

Lead sponsorIntra-Cellular Therapies, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment488
Start date27 February 2020
Primary completion30 November 2022
Estimated completion30 November 2022
Sites42 locations across Russia, Ukraine, Serbia, Bulgaria, United States

Drugs / interventions tested

Conditions studied

Sponsor

Intra-Cellular Therapies, Inc. — full company profile →

Who can join

Adults 18 to 75, any sex, with Bipolar Depression or Major Depressive Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Primary · Day 43

The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

GroupValue95% CI
Lumateperone 42mg-18.1± 0.71
Placebo-12.4± 0.70
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Primary · Day 43

The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

GroupValue95% CI
Lumateperone 42mg-17.7± 1.00
Placebo-12.0± 0.96
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Primary · Day 43

The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

GroupValue95% CI
Lumateperone 42mg-18.2± 0.95
Placebo-12.2± 0.96
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Primary · Day 43

The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

GroupValue95% CI
Lumateperone 42mg-17.7± 0.64
Placebo-12.1± 0.63
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Secondary · Day 43

The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

GroupValue95% CI
Lumateperone 42mg-1.8± 0.08
Placebo-1.2± 0.08
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Secondary · Day 43

The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

GroupValue95% CI
Lumateperone 42mg-1.8± 0.11
Placebo-1.2± 0.11
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Secondary · Day 43

The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

GroupValue95% CI
Lumateperone 42mg-1.7± 0.11
Placebo-1.1± 0.11
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Secondary · Day 43

The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

GroupValue95% CI
Lumateperone 42mg-1.7± 0.07
Placebo-1.1± 0.07

Adverse events — posted to ClinicalTrials.gov

Time frame: From signing ICF until end of study procedures (~10 weeks), including 6 weeks of double-blind treatment.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lumateperone 42mg
Serious: 0/240 (0%)
Deaths: 0/240
Placebo
Serious: 1/241 (0%)
Deaths: 0/241

Serious adverse events (1 terms)

ReactionSystemLumateperone 42mgPlacebo
DermatitisSkin and subcutaneous tissue disorders
Other adverse events (4 terms — click to expand)

ReactionSystemLumateperone 42mgPlacebo
HeadacheNervous system disorders
SomnolenceNervous system disorders
DizzinessNervous system disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Dermatitis.

Data from ClinicalTrials.gov NCT04285515 adverse events section.

Sponsor's own description

This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of lumateperone monotherapy in the treatment of patients with major depressive episodes associated with Bipolar I or Bipolar II Disorder (Bipolar Depression) or major depressive disorder (MDD) who also meet the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5) criteria for mixed-features. The study consists of a Screening Period, a Double-blind Treatment Period, and a Safety Follow-up Period.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Lumateperone for the Treatment of Major Depressive Disorder With Mixed Features or Bipolar Depression With Mixed Features: A Randomized Placebo-Controlled Trial.
    Durgam S, Kozauer SG, Earley WR, Chen C, et al · · 2025 · cited 8× · PMID 39946099 · DOI 10.1097/jcp.0000000000001964
  2. Dose-response efficacy and safety of lumateperone in bipolar depression: A preliminary meta-analysis of randomized controlled trials.
    Hsu CW, Tu YK, Hung KC, Liang CS, et al · · 2025 · cited 1× · PMID 40874771 · DOI 10.1177/02698811251364389
  3. Efficacy and safety of lumateperone for bipolar depression and schizophrenia: a systematic review and meta-analysis.
    Peng H, Yan K, Liu S, Li X, et al · · 2024 · cited 1× · PMID 39487717 · DOI 10.1093/ijnp/pyae052
  4. The efficacy of lumateperone across symptoms of a major depressive episode with mixed features in patients with major depressive disorder and bipolar disorder: Post hoc analyses.
    Yatham LN, Kozauer SG, Earley WR, Huo J, et al · · 2026 · PMID 41740754 · DOI 10.1016/j.jad.2026.121499
  5. ACNP 63rd Annual Meeting: Poster Abstracts P1-P304
    · 2024
  6. LUMATEPERONE TREATMENT FOR MAJOR DEPRESSIVE EPISODES WITH MIXED FEATURES IN MAJOR DEPRESSIVE DISORDER AND BIPOLAR I OR BIPOLAR II DISORDER
    · 2025
  7. EFFECT MODIFICATION OF TUMOR NECROSIS FACTOR-α ON THE KYNURENINE AND SEROTONIN PATHWAYS IN MAJOR DEPRESSIVE DISORDER ON TYPE 2 DIABETES MELLITUS
    · 2025
  8. LUMATEPERONE IN THE TREATMENT OF PATIENTS WITH MAJOR DEPRESSIVE DISORDER AND BIPOLAR DISORDER WITH ANXIOUS DISTRESS AND MIXED FEATURES
    · 2025

Verify or expand the search:

Other trials of Lumateperone

Trials testing the same drug.

Other recruiting trials for Bipolar Depression

Currently open trials in the same condition.

Other Intra-Cellular Therapies, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04285515.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing