Clinical trial NCT05850689: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Adjunctive MDD Therapy
Lead sponsor: Intra-Cellular Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-09
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: Day 43
Secondary outcomes:
measure: Clinical Global Impression Scale-Severity
timeFrame: Day 43
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clinical Site
state: Alabama
city: Pico Rivera
country: United States
facility: Clinical Site
state: California
city: Farmington
country: United States
facility: Clinical Site
state: Connecticut
city: Clermont
country: United States
facility: Clinical Site
state: Florida
city: Hialeah
country: United States
facility: Clinical Site
state: Florida
city: Miami
country: United States
facility: Clinical Site
state: Florida
city: Miami
country: United States
facility: Clinical Site
state: Florida
city: Miami
country: United States
facility: Clinical Site
state: Florida
city: Tampa
country: United States
facility: Clinical Site
state: Florida
city: Atlanta
country: United States
facility: Clinical Site
state: Georgia
city: Decatur
country: United States
facility: Clinical Site
state: Georgia
city: Kansas City
country: United States
facility: Clinical Site
state: Kansas
city: Kansas City
country: United States
facility: Clinical Site
state: Kansas
city: Overland Park
country: United States
facility: Clinical Site
state: Kansas
city: Methuen
country: United States
facility: Clinical Site
state: Massachusetts
city: O'Fallon
country: United States
facility: Clinical Site
state: Missouri
city: New York
country: United States
facility: Clinical Site
state: New York
city: Avon Lake
country: United States
facility: Clinical Site
state: Ohio
city: Cincinnati
country: United States
facility: Clinical Site
state: Ohio
city: Columbus
country: United States
facility: Clinical Site
state: Ohio
city: Philadelphia
country: United States
facility: Clinical Site
state: Pennsylvania
city: Houston
country: United States
facility: Clinical Site
state: Texas
city: Richardson
country: United States
facility: Clinical Site
state: Texas
city: Bellevue
country: United States
facility: Clinical Site
state: Washington
city: Cherven Bryag
country: Bulgaria
facility: Clinical Site
city: Kardzhali
country: Bulgaria
facility: Clinical Site
city: Pleven
country: Bulgaria
facility: Clinical Site
city: Sofia
country: Bulgaria
facility: Clinical Site
city: Sofia
country: Bulgaria
facility: Clinical Site
city: Sofia
country: Bulgaria
facility: Clinical Site
city: Stara Zagora
country: Bulgaria
facility: Clincal Site
city: Varna
country: Bulgaria
facility: Clinical Site
city: Kaunas
country: Lithuania
facility: Clinical Site
city: Ziegzdriai
country: Lithuania
facility: Clinical Site
city: Barcelona
country: Spain
facility: Clinical Site
city: Madrid
country: Spain
facility: Clinical Site
city: Zamora
country: Spain
facility: Clinical Site
Study officials:
References: