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

• ClinicalTrials.gov Identifier: NCT05850689
• Recruitment Status: Recruiting
• First Posted: May 9, 2023
• Last Update Posted: January 10, 2024
• Sponsor: Intra-Cellular Therapies, Inc.
• Information provided by (Responsible Party): Intra-Cellular Therapies, Inc.

Tracking Information

• First Submitted Date: April 28, 2023
• First Posted Date: May 9, 2023
• Last Update Posted Date: January 10, 2024
• Actual Study Start Date: May 2, 2023
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2023)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 29, 2023)

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).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
• 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
• 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

• Drug: Lumateperone
  Lumateperone 42 mg capsules administered orally, once daily
• Drug: Placebo
  Matching capsules administered orally, once daily

Study Arms

• Experimental: Lumateperone 42 mg
  Intervention: Drug: Lumateperone
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2023): 470
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2025
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 8 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 to ADT (less than 50% improvement) 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ITI Clinical Trials; 646 440-9333; ITCIClinicalTrials@itci-inc.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05850689
• Other Study ID Numbers: ITI-007-505
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Intra-Cellular Therapies, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Intra-Cellular Therapies, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Intra-Cellular Therapies, Inc.
• Verification Date: January 2024