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Major Depressive DisorderPhase 3NCT04985942

Clinical Trial of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

A Phase 3 study testing Lumateperone in people with Major Depressive Disorder, run by Intra-Cellular Therapies, Inc. at 54 sites in 6 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

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
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
485 participants
Where
54 sitesin 6 countries
Study dates
30 Jul 2021to 27 Feb 2024
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients between the ages of 18 and 65 years, inclusive;
  • Meet DSM-5 diagnostic criteria for MDD (a diagnosis of MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor-approved rater using the Mini-International Neuropsychiatric Interview (MINI), and meet all the following criteria:
  • The start of the current major depressive episode (MDE) is at least 8 weeks but not more than 18 months prior to Screening;
  • Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening and at Baseline;
  • Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening and at Baseline;
  • Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14 at Screening and at Baseline;
Show all 18Show fewer
  • Has sufficient history and medical record confirmation verifying the ADT and the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  • Currently having an inadequate response to ADT (less than 50% improvement) as confirmed by the Investigator and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration:
  • citalopram/escitalopram
  • fluoxetine
  • paroxetine
  • sertraline
  • duloxetine
  • levomilnacipran/milnacipran (if locally approved for MDD)
  • venlafaxine/desvenlafaxine
  • buproprion
  • vilazodone
  • vortioxetine

Who cannot join

  • Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including:
  • Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder;
  • Bipolar Disorder;
  • Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including:
  • Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses.
  • Eating disorder;
Show all 17Show fewer
  • Substance use disorders (excluding nicotine);
  • Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status;
  • Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment;
  • The patient experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline;
  • The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;
  • In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or:
  • At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit;
  • At Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening;
  • At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or
  • The patient is considered to be in imminent danger to him/herself or others.
  • The patient has a first MDE at age 60 years or older.

Trial locations and contacts

54 sites in 6 countries.

54 sites in 6 countries

United States15 sites

  • Clinical Site

    Austin, Texas, 78737

  • Clinical Site

    Berlin, New Jersey, 08009

  • Clinical Site

    Boston, Massachusetts, 02131

  • Clinical Site

    Cedarhurst, New York, 11516

  • Clinical Site

    Decatur, Georgia, 30030

  • Clinical Site

    Fort Lauderdale, Florida, 33319

  • Clinical Site

    Glendale, California, 91206

  • Clinical Site

    Jacksonville, Florida, 32256

  • Clinical Site

    Oceanside, California, 92056

  • Clinical Site

    Orlando, Florida, 32801

  • Clinical Site

    Phoenix, Arizona, 85012

  • Clinical Site

    Redlands, California, 92374

  • Clinical Site

    Temecula, California, 92591

  • Clinical Site

    Toms River, New Jersey, 08755

  • Clinical Site

    Upland, California, 91786

Other trials in United States

India15 sites

  • Clinical Site

    Ahmedabad, Gujarat, 380013

  • Clinical Site

    Chhatrapati Sambhajinagar, Maharashtra, 431005

  • Clinical Site

    Guwahati, Assam, 781011

  • Clinical Site

    Jaipur, Rajasthan, 302017

  • Clinical Site

    Jūnāgadh, Gujarat, 362001

  • Clinical Site

    Kozhikode, Kerala, 673009

  • Clinical Site

    Lucknow, Uttar Pradesh, 226003

  • Clinical Site

    Ludhiana, Punjab, 141001

  • Clinical Site

    Mangaluru, Karnataka, 575003

  • Clinical Site

    Mysore, Karnataka, 570001

  • Clinical Site

    Nagpur, Maharashtra, 440010

  • Clinical Site

    Nashik, Maharashtra, 422005

  • Clinical Site

    Nashik, Maharashtra, 422101

  • Clinical Site

    Vadodara, Gujarat, 390021

  • Clinical Site

    Varanasi, Uttar Pradesh, 221005

Other trials in India

Bulgaria8 sites

  • Clinical Site

    Burgas, 8001

  • Clinical Site

    Kazanlak, 6100

  • Clinical Site

    Pleven, 5809

  • Clinical Site

    Rousse, 7003

  • Clinical Site

    Tsarev Brod, 9747

  • Clinical Site

    Veliko Tarnovo, 5000

  • Clinical Site

    Veliko Tarnovo, 5047

  • Clinical Site

    Vratsa, 3001

Other trials in Bulgaria

Czechia6 sites

  • Clinical Site

    Brno, 60200

  • Clinical Site

    Brno, 615 000

  • Clinical Site

    Ostrava, 70800

  • Clinical site

    Pilsen, 301 00

  • Clinical Site

    Prague, 160 00

  • Clinical Site

    Prague, 186 00

Other trials in Czechia

Slovakia6 sites

  • Clinical Site

    Bratislava, 82007

  • Clinical Site

    Košice, 04001

  • Clinical Site

    Rimavská Sobota, 979 01

  • Clinical Site

    Svidník, 089 01

  • Clinical Site

    Vranov nad Topľou, 09301

  • Clinical Site

    Zlaté Moravce, 953 01

Other trials in Slovakia

Hungary4 sites

  • Clinical Site

    Budapest, 1033

  • Clinical Site

    Budapest, 1083

  • Clinical Site

    Budapest, 1134

  • Clinical Site

    Gyöngyös, 3200

Other trials in Hungary

About this study

Official title: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT.

Read the detailed description

The study will be conducted in three periods:

  • Screening Period (up to 2 weeks) during which patient eligibility will be assessed;
  • Double-blind Treatment Period (6 weeks) in which all patients will be randomized to receive placebo or lumateperone 42mg/day in 1:1 ratio.
  • Safety Follow-up Period (1 week) in which all patients will return to the clinic for a safety follow-up visit approximately one week after the last dose of study treatment.
Being tested
Lumateperone, Placebo
Keywords
Adjunctive MDD Therapy
Medical subject headings
Depressive Disorder, Major

What participants receive

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

  • LumateperoneDrug

    Lumateperone 42 mg capsules administered orally, once daily.

  • PlaceboDrug

    Matching capsules administered orally, once daily.

Study groups in NCT04985942
Study groupRoleWhat they receive
Lumateperone 42 mgExperimentalNot described
Receives: Drug: Lumateperone
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

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

  1. Montgomery-Åsberg Depression Rating Scale

    Change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The MADRS 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)

  1. Clinical Global Impression Scale-Severity

    Change from baseline to Day 43 in the Clinical Global Impression Scale-Severity (CGI-S). The CGI-S 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.

  1. First posted2 Aug 2021
  2. Study start30 Jul 2021
  3. Primary completion22 Feb 2024
  4. Study completion27 Feb 2024

Resources

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
485 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04985942
Sponsor's protocol ID
ITI-007-501
Status last verified
May 2025
First submitted
22 Jul 2021
Last updated
2 May 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sachs GS, Durgam S, Earley WR, Kozauer SG, Chen C, Masand P. Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of a Phase 3, Randomized, Double-Blind Trial. J Clin Psychiatry. 2026 Sep 14;87(3):26m16409. doi: 10.4088/JCP.26m16409.

    PubMed 42752587

  • Earley WR, Durgam S, Kozauer SG, Chen C, Migliore R, Correll CU. Safety and Tolerability of Adjunctive Lumateperone for the Treatment of Major Depressive Disorder: A Pooled Analysis of Two Randomized Placebo-Controlled Trials. CNS Drugs. 2026 Jul 15. doi: 10.1007/s40263-026-01314-8. Online ahead of print.

    PubMed 42455478

  • Durgam S, Earley WR, Kozauer SG, Chen C, Lakkis H, McIntyre RS, Stahl S. Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder: Results From a Randomized, Double-Blind, Phase 3 Trial. J Clin Psychiatry. 2025 Aug 25;86(4):25m15848. doi: 10.4088/JCP.25m15848.

    PubMed 40875502

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lumateperone in people with Major Depressive Disorder, run by Intra-Cellular Therapies, Inc. at 54 sites in 6 countries.

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

Who may be eligible to take part?

The sponsor lists 18 inclusion and 17 exclusion criteria. 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 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States, India, Bulgaria, Czechia, Slovakia and 1 more country. 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 2 May 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?

Montgomery-Åsberg Depression Rating Scale (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 NCT04985942, which also lists 3 linked publications.

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 2 May 2025.

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