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

NCT04985942 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ITI-007-501
• Study Type: interventional
• Target: 485
• Locations: 6 countries
• Sites: 54

Brief 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.

Conditions

Major Depressive Disorder

Keywords

Adjunctive MDD Therapy

Outcome Measures

Primary Outcomes (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.

  Day 43

Secondary Outcomes (1)

• Clinical Global Impression Scale-Severity

  Day 43

Study Arms (2)

Lumateperone 42 mg

EXPERIMENTAL

Drug: Lumateperone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Lumateperone DRUG

Lumateperone 42 mg capsules administered orally, once daily.

Lumateperone 42 mg

Placebo DRUG

Matching capsules administered orally, once daily.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Intra-Cellular Therapies, Inc.: lead

Study Sites (54)

Clinical Site

Phoenix, Arizona, 85012, United States

Location

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Glendale, California, 91206, United States

Location

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Oceanside, California, 92056, United States

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Redlands, California, 92374, United States

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Temecula, California, 92591, United States

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Upland, California, 91786, United States

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Fort Lauderdale, Florida, 33319, United States

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Jacksonville, Florida, 32256, United States

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Orlando, Florida, 32801, United States

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Decatur, Georgia, 30030, United States

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Boston, Massachusetts, 02131, United States

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Berlin, New Jersey, 08009, United States

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Toms River, New Jersey, 08755, United States

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Cedarhurst, New York, 11516, United States

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Austin, Texas, 78737, United States

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Burgas, 8001, Bulgaria

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Kazanlak, 6100, Bulgaria

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Pleven, 5809, Bulgaria

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Rousse, 7003, Bulgaria

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Tsarev Brod, 9747, Bulgaria

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Veliko Tarnovo, 5000, Bulgaria

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Veliko Tarnovo, 5047, Bulgaria

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Vratsa, 3001, Bulgaria

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Brno, 60200, Czechia

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Brno, 615 000, Czechia

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Ostrava, 70800, Czechia

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Pilsen, 301 00, Czechia

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Prague, 160 00, Czechia

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Prague, 186 00, Czechia

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Budapest, 1033, Hungary

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Budapest, 1083, Hungary

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Budapest, 1134, Hungary

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Gyöngyös, 3200, Hungary

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Guwahati, Assam, 781011, India

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Ahmedabad, Gujarat, 380013, India

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Jūnāgadh, Gujarat, 362001, India

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Vadodara, Gujarat, 390021, India

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Mangaluru, Karnataka, 575003, India

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Mysore, Karnataka, 570001, India

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Kozhikode, Kerala, 673009, India

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Aurangabad, Maharashtra, 431005, India

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Nagpur, Maharashtra, 440010, India

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Nashik, Maharashtra, 422005, India

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Nashik, Maharashtra, 422101, India

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Ludhiana, Punjab, 141001, India

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Jaipur, Rajasthan, 302017, India

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Lucknow, Uttar Pradesh, 226003, India

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Varanasi, Uttar Pradesh, 221005, India

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Bratislava, 82007, Slovakia

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Košice, 04001, Slovakia

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Rimavská Sobota, 979 01, Slovakia

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Svidník, 089 01, Slovakia

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Vranov nad Topľou, 09301, Slovakia

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Clinical Site

Zlaté Moravce, 953 01, Slovakia

Location

Related Publications (1)

• 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.

  PMID: 40875502 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

lumateperone

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: ITI Clinical Trials
• Organization: Intra-Cellular Therapies, Inc.

ITCIClinicalTrials@itci-inc.com

646 440-9333

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 2, 2021
• Study Start: July 30, 2021
• Primary Completion: February 22, 2024
• Study Completion: February 27, 2024
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

BU (8); IN (15); HU (4); US (15); CZ (6); SL (6)