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

August 27, 2026 updated by: Intra-Cellular Therapies, Inc.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 42 mg/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.

Study Type

Interventional

Enrollment (Estimated)

470

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Bulgaria
      • Cherven Bryag, Bulgaria, 5980
        • Recruiting
        • Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET
      • Kardzhali, Bulgaria, 6600
        • Recruiting
        • Medical Center Lifemed
      • Pleven, Bulgaria, 5800
        • Recruiting
        • Medical Center Medconsult-Pleven
      • Plovdiv, Bulgaria, 4004
        • Recruiting
        • Medical Center Mentalcare OOD
      • Sofia, Bulgaria, 1680
        • Recruiting
        • Medical Center Intermedica, OOD
      • Sofia, Bulgaria, 1510
        • Recruiting
        • Medical Center Hera EOOD
      • Sofia, Bulgaria, 1202
        • Recruiting
        • MHC - Sofia, EOOD
      • Sofia, Bulgaria, 1431
        • Terminated
        • University Multiprofile Hospital for Active Treatment - UMHAT Alexandrovska EAD
      • Stara Zagora, Bulgaria, 6003
        • Completed
        • UMHAT Prof. Dr. St. Kirkovich AD
      • Varna, Bulgaria, 9020
        • Recruiting
        • Diagnostic Consulting Center Mladost - M Varna
  • France
      • Douai, France, 59500
        • Recruiting
        • Cabinet Medical des Drs Prizac-Desbonnet Scottez
      • Nantes, France, 44093
        • Recruiting
        • CHU de Nantes hotel Dieu
      • Nîmes, France, 30029
        • Recruiting
        • Hopital Caremeau
      • Paris, France, 75012
        • Recruiting
        • Groupe Hospitalier Pitie-Salpetriere
      • Poitiers, France, 86021
        • Recruiting
        • CH Henri Laborit
  • India
      • Ahmedabad, India, 380008
        • Suspended
        • Ratandeep Surgical Hospital And Endoscopy Clinic
      • Ahmedabad, India, 380009
        • Suspended
        • Sushrusha Navneet Memorial Hospital
      • Ajmer, India, 305001
        • Suspended
        • J L N Medical College and Attached Hospitals
      • Bikaner, India, 334001
        • Recruiting
        • S P Medical College And Associated Group of Hospitals
      • Bārāmati, India, 413102
        • Recruiting
        • Baramati Hospital
      • Chandigarh, India, 160012
        • Recruiting
        • Post Graduate Institute of Medical Education And Research PGIMER
      • Guwahati, India, 781032
        • Completed
        • Gauhati Medical College and Hospital
      • Kolhāpur, India, 416001
        • Recruiting
        • Swastik Hospital
      • Nagpur, India, 440001
        • Recruiting
        • KIMS-Kingsway Hospitals
      • Palsāna, India, 394315
        • Recruiting
        • Divyam Hospital
      • Pune, India, 411011
        • Recruiting
        • Shree Samarth Hospital
      • Rajkot, India, 360001
        • Completed
        • Nagecha Hospital
      • Wardha, India, 442004
        • Suspended
        • Acharya Vinoba Bhave Rural Hospital
  • Lithuania
      • Kaunas, Lithuania, LT-44279
        • Completed
        • Romuvos Klinika, JSC
      • Ziegzdriai, Lithuania, 53136
        • Completed
        • Kaunas Hospital of Lithuanian University of Health Sciences Psychiatric Clinic Mariu division
  • Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • University Clinical Center of Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Institute of Mental Health Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Clinical Center Dr Dragisa Misovic Dedinje
      • Kovin, Serbia, 26220
        • Recruiting
        • Special Hospital for Psychiatric Diseases Kovin
      • Kragujevac, Serbia, 34000
        • Recruiting
        • University Clinical Center Kragujevac
      • Kragujevac, Serbia, 34000
        • Recruiting
        • University Clinical Center Kragujevac 1
      • Niš, Serbia, 18000
        • Recruiting
        • University Clinical Center Nis
      • Niš, Serbia, 18000
        • Recruiting
        • University Clinical Center NIS 1
      • Novi Kneževac, Serbia, 23330
        • Recruiting
        • Special Hospital for Psychiatric Diseases Sveti Vracevi
  • Spain
      • Barcelona, Spain, 08036
        • Recruiting
        • Hosp. Clinic de Barcelona
      • Barcelona, Spain, 08035
        • Recruiting
        • Hosp Univ Vall D Hebron
      • Madrid, Spain, 28034
        • Recruiting
        • Hosp. Univ. Ramon Y Cajal
      • Sabadell, Spain, 08208
        • Recruiting
        • Hosp.Univ.Parc Tauli
      • Zamora, Spain, 49021
        • Recruiting
        • Hosp. Prov. de Zamora
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35801
        • Recruiting
        • University of Alabama at Birmingham
    • California
      • Pico Rivera, California, United States, 90660
        • Recruiting
        • CNRI-Los Angeles, LLC
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • Recruiting
        • University of Connecticut Health Center
    • Florida
      • Clermont, Florida, United States, 34711
        • Terminated
        • Vertex Clinical Research
      • Hialeah, Florida, United States, 33012
        • Suspended
        • New Life Medical Research Center, Inc.
      • Miami, Florida, United States, 33122
        • Recruiting
        • Premier Clinical Research Institute
      • Miami, Florida, United States, 33137
        • Recruiting
        • Miami Jewish Health System
      • Tampa, Florida, United States, 33629
        • Recruiting
        • Interventional Psychiatry of Tampa Bay
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • The Emory Clinic
      • Decatur, Georgia, United States, 30030
        • Recruiting
        • CenExeli Research LLC
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Terminated
        • University of Kansas Medical Center Research Institute
      • Overland Park, Kansas, United States, 66210
        • Recruiting
        • Collective Medical Research
    • Massachusetts
      • Methuen, Massachusetts, United States, 01844
        • Terminated
        • ActivMed Practices and Research
    • Missouri
      • O'Fallon, Missouri, United States, 63368
        • Recruiting
        • Psychiatric Care and Research Center (PCRC)
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Recruiting
        • Bio Behavioral Health
    • New York
      • Brooklyn, New York, United States, 11235
        • Recruiting
        • SPRI Clinical Trials, LLC
      • New York, New York, United States, 10036
        • Recruiting
        • Manhattan Behavioral Medicine
    • Ohio
      • Avon Lake, Ohio, United States, 44012
        • Recruiting
        • Quest Therapeutics of Avon Lake
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania - Perelman School of Medicine
    • Texas
      • Houston, Texas, United States, 77081
        • Recruiting
        • DM Clinical Research
      • Mansfield, Texas, United States, 76063
        • Completed
        • Hawkins Psychiatry, PC
      • Richardson, Texas, United States, 75080
        • Recruiting
        • Pillar Clinical Research, LLC
    • Washington
      • Bellevue, Washington, United States, 98007
        • Recruiting
        • Northwest Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female patients between the ages of 18 and 65 years, inclusive;

  2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria:

    1. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than 18 months prior to Screening;
    2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening and at Baseline;
    3. Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening and at Baseline;
    4. Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening and at Baseline;
    5. 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.

  3. Currently having an inadequate response (less than 50% improvement) to 2 or more ADTs in the current MDE as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) 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:

    1. citalopram/escitalopram
    2. fluoxetine
    3. paroxetine
    4. sertraline
    5. duloxetine
    6. levomilnacipran/milnacipran (if locally approved for MDD)
    7. venlafaxine/desvenlafaxine
    8. bupropion
    9. vilazodone
    10. vortioxetine

Exclusion Criteria:

  1. Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including:

    1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder;
    2. Bipolar Disorder;

  2. Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including:

    1. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment;
    2. Eating disorder;
    3. Substance use disorders (excluding nicotine);
    4. Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status;
    5. Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment;
  3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline;
  4. The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;

  5. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or:

    1. 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;
    2. At Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening;
    3. At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or
    4. The patient is considered to be in imminent danger to him/herself or others.
  6. The patient has a first MDE at age 60 years or older.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Matching capsules administered orally, once daily
Experimental: Lumateperone 42 mg
Drug: Lumateperone
Lumateperone 42 mg capsules administered orally, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale
Time Frame: Day 43
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.
Day 43

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression Scale-Severity
Time Frame: Day 43
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).
Day 43

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intra-Cellular Therapies, Inc.

Investigators

  • Study Director: Intra-Cellular Therapies, Inc. Clinical Trial, Intra-Cellular Therapies, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2023

Primary Completion (Estimated)

April 5, 2027

Study Completion (Estimated)

April 5, 2027

Study Registration Dates

First Submitted

April 28, 2023

First Submitted That Met QC Criteria

April 29, 2023

First Posted (Actual)

May 9, 2023

Study Record Updates

Last Update Posted (Actual)

August 28, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ITI-007-505 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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