Bipolar DepressionPhase 3NCT04285515

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

A Phase 3 study testing Lumateperone in people with Bipolar Depression and Major Depressive Disorder, run by Intra-Cellular Therapies, Inc. at 42 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Bipolar Depression, Major Depressive Disorder
What is being tested?: Lumateperone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 488 participants
Where: 42 sitesin 5 countries
Study dates: 27 Feb 2020to 30 Nov 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Major Inclusion Criteria:

Male or female subjects of any race, ages 18-75 inclusive
Meets the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM 5) criteria for Bipolar I or Bipolar II Disorder or MDD
The start of the current major depressive episode is at least 2 weeks but no more than 6 months prior to the Screening (Visit 1)
Has at least moderate severity of illness, as measured by a rater-administered MADRS total score ≥ 24 and corresponding to a CGI S score of ≥ 4 at Screening (Visit 1) and Baseline (Visit 2)
The patient meets the DSM-5 criteria for mixed-features specific to the Bipolar I or II diagnosis or MDD diagnosis
Current major depressive episode is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning
Able to provide written informed consent

Major Exclusion Criteria:

Any female subject who is pregnant or breast-feeding
Any subject judged to be medically inappropriate for study participation
The patient has a significant risk for suicidal behavior
The patient presents with a lifetime history of epilepsy, seizure or convulsion, or electroencephalogram with clinically significant abnormalities, delirium, dementia, amnestic, or other cognitive disorder or significant brain trauma

Trial locations and contacts

42 sites in 5 countries.

Country

City, postcode or hospital

42 sites in 5 countries

United States13 sites

Clinical Site
Atlanta, Georgia, 30331
Clinical Site
Bellevue, Washington, 98007
Clinical Site
Cedarhurst, New York, 11694
Clinical Site
Charlotte, North Carolina, 28211
Clinical Site
Decatur, Georgia, 30030
Clinical Site
Garden Grove, California, 92845
Clinical Site
Lauderhill, Florida, 33319
Clinical Site
Miami, Florida, 33122
Clinical Site
New York, New York, 10128
Clinical Site
O'Fallon, Missouri, 63368
Clinical Site
Oceanside, California, 92056
Clinical Site
Orange City, Florida, 32763
Clinical Site
Sherman Oaks, California, 91403

Other trials in United States

Bulgaria11 sites

Clinical Site
Burgas, 8000
Clinical Site
Kardzhali, 6600
Clinical Site
Plovdiv, 4004
Clinical Site
Rousse, 7003
Clinical Site
Sofia, 1113
Clinical Site
Sofia, 1408
Clinical Site
Sofia, 1431
Clinical Site
Sofia, 1680
Clinical Site
Varna, 9020
Clinical Site
Veliko Tarnovo, 5000
Clinical Site
Vratsa, 3000

Other trials in Bulgaria

Russia8 sites

Clinical Site
Moscow, 105082
Clinical Site
Saint Petersburg, 190121
Clinical Site
Saint Petersburg, 192019
Clinical Site
Saint Petersburg, 195160
Clinical Site
Saint Petersburg, 197341
Clinical Site
Saint Petersburg, 199106
Clinical Site
Tomsk, 634009
Clinical Site
Yekaterinburg, 620030

Other trials in Russia

Ukraine7 sites

Clinical Site
Kyiv, 1133
Clinical Site
Lviv, 79021
Clinical site
Odesa, 65006
Clinical Site
Odesa, 67513
Clinical Site
Poltava, 36013
Clinical Site
Smila, 20708
Clinical Site
Vinnytsia, 21005

Other trials in Ukraine

Serbia3 sites

Clinical Site
Belgrade, 11000
Clinical Site
Kovin, 26220
Clinical Site
Kragujevac, 34000

Other trials in Serbia

About this study

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess 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

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.

Conditions: Bipolar Depression, Major Depressive Disorder
Being tested: Lumateperone, Placebos
Keywords: Mixed Features
Medical subject headings: Bipolar Disorder, Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LumateperoneDrug
Lumateperone 42mg oral capsule
PlacebosDrug
Placebo oral capsule

Study groups in NCT04285515
Study group	Role	What they receive
Lumateperone 42mg	Experimental	Lumateperone 42mg administered once daily in the evening Receives: Drug: Lumateperone
Placebo	Placebo comparator	Matching placebo administered once daily in the evening Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
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.
Measured: Day 43

Secondary outcomes (1)

Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S)
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).
Measured: Day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Feb 202030 Nov 2022

First posted26 Feb 2020
Study start27 Feb 2020
Primary completion30 Nov 2022
Study completion30 Nov 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Bipolar DepressionStudies of the same condition, open and under way.
More trials run by Intra-Cellular Therapies, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 488 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04285515
Sponsor's protocol ID: ITI-007-403
Status last verified: Mar 2025
First submitted: 24 Feb 2020
Last updated: 19 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Durgam S, Kozauer SG, Earley WR, Chen C, Huo J, Lakkis H, Stahl S, McIntyre RS. Lumateperone for the Treatment of Major Depressive Disorder With Mixed Features or Bipolar Depression With Mixed Features: A Randomized Placebo-Controlled Trial. J Clin Psychopharmacol. 2025 Mar-Apr 01;45(2):67-75. doi: 10.1097/JCP.0000000000001964. Epub 2025 Feb 14.
PubMed 39946099

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Safety and Feasibility of DBS for Bipolar Depression
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Affective Cognitive Training in Mood Disorders and High-risk Relatives
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All Bipolar Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess 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
ClinicalTrials.gov ID: NCT04285515
Acronym / sponsor ID: ITI-007-403
Conditions: Bipolar Depression, Major Depressive Disorder
Keywords: Mixed Features
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 488 participants (actual)
Lead sponsor: Intra-Cellular Therapies, Inc.Industry (pharma, biotech, devices)
Study start: 27 Feb 2020 (actual)
Primary completion: 30 Nov 2022 (actual)
Study completion: 30 Nov 2022 (actual)
First posted: 26 Feb 2020 (actual)
Results: Posted 19 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Lumateperone 42mg	Experimental	Drug: LumateperoneLumateperone 42mg administered once daily in the evening
Placebo	Placebo comparator	Drug: PlacebosMatching placebo administered once daily in the evening

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LumateperoneLumateperone 42mg oral capsule	Drug	Lumateperone 42mg
PlacebosPlacebo oral capsule	Drug	Placebo

Primary outcome

Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Time frame: 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.

1 secondary outcome

Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S)
Time frame: Day 43

Results and safety

Results posted to the registry on 19 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lumateperone 42mg	243	211
Placebo	245	217

Primary outcome: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

Time frame: Day 43. Least squares mean (Standard Error). Unit: score on a scale

Measure	Lumateperone 42mg n = 192	Placebo n = 191
Value	-18.1 (0.71)	-12.4 (0.70)

Lumateperone 42mg vs Placebo: Least Squares Mean Difference: -5.7 (95% CI -7.60 to -3.84), p <0.0001, Mixed Effects Model for Repeated Measure

Population analysed: Combined MDD and Bipolar Depression Mixed Features Population

Primary outcome: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

Time frame: Day 43. Least squares mean (Standard Error). Unit: score on a scale

Measure	Lumateperone 42mg n = 100	Placebo n = 99
Value	-17.7 (1.00)	-12.0 (0.96)

Lumateperone 42mg vs Placebo: Least Squares Mean Difference: -5.7 (95% CI -8.29 to -3.05), p <0.0001, Mixed Effects Model for Repeated Measure

Population analysed: Bipolar Depression Mixed Features Population

Primary outcome: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

Time frame: Day 43. Least squares mean (Standard Error). Unit: score on a scale

Measure	Lumateperone 42mg n = 92	Placebo n = 92
Value	-18.2 (0.95)	-12.2 (0.96)

Lumateperone 42mg vs Placebo: Least Squares Mean Difference: -5.9 (95% CI -8.61 to -3.29), p <0.0001, Mixed Effects Model for Repeated Measure

Population analysed: MDD Mixed Features Population

Primary outcome: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

Time frame: Day 43. Least squares mean (Standard Error). Unit: score on a scale

Measure	Lumateperone 42mg n = 239	Placebo n = 238
Value	-17.7 (0.64)	-12.1 (0.63)

Lumateperone 42mg vs Placebo: Least Squares Mean Difference: -5.6 (95% CI -7.25 to -3.88), p <0.0001, Mixed Effects Model for Repeated Measure

Population analysed: Overall Population

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From signing ICF until end of study procedures (~10 weeks), including 6 weeks of double-blind treatment.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lumateperone 42mg	0 of 240 (0%)	84 of 240 (35%)	0 of 240
Placebo	1 of 241 (0.4%)	37 of 241 (15.4%)	0 of 241

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39946099Durgam S, Kozauer SG, Earley WR, Chen C, Huo J, Lakkis H, Stahl S, McIntyre RS. Lumateperone for the Treatment of Major Depressive Disorder With Mixed Features or Bipolar Depression With Mixed Features: A Randomized Placebo-Controlled Trial. J Clin Psychopharmacol. 2025 Mar-Apr 01;45(2):67-75. doi: 10.1097/JCP.0000000000001964. Epub 2025 Feb 14.
Individual participant dataSharing planned: No

Related trials for Bipolar Depression

Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)
RecruitingPhase 3
Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients
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RecruitingObservational study
Natural History of Depression, Bipolar Disorder and Suicide Risk
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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Susan Kozauer, MD study director

Intra-Cellular Therapies, Inc.

42 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lumateperone in people with Bipolar Depression and Major Depressive Disorder, run by Intra-Cellular Therapies, Inc. at 42 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States, Bulgaria, Russia, Ukraine, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score (time frame: Day 43). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04285515, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.