Clinical trial NCT04985942: Clinical Trial 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: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Adjunctive MDD Therapy
Lead sponsor: Intra-Cellular Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-02
Enrollment: 485
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 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients between the ages of 18 and 65 years, inclusive;
2. 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:

   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 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. buproprion
   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.
   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-Åsberg Depression Rating Scale
timeFrame: Day 43
Secondary outcomes:
measure: Clinical Global Impression Scale-Severity
timeFrame: Day 43
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Site
state: Arizona
city: Glendale
country: United States
facility: Clinical Site
state: California
city: Oceanside
country: United States
facility: Clinical Site
state: California
city: Redlands
country: United States
facility: Clinical Site
state: California
city: Temecula
country: United States
facility: Clinical Site
state: California
city: Upland
country: United States
facility: Clinical Site
state: California
city: Fort Lauderdale
country: United States
facility: Clinical Site
state: Florida
city: Jacksonville
country: United States
facility: Clinical Site
state: Florida
city: Orlando
country: United States
facility: Clinical Site
state: Florida
city: Decatur
country: United States
facility: Clinical Site
state: Georgia
city: Boston
country: United States
facility: Clinical Site
state: Massachusetts
city: Berlin
country: United States
facility: Clinical Site
state: New Jersey
city: Toms River
country: United States
facility: Clinical Site
state: New Jersey
city: Cedarhurst
country: United States
facility: Clinical Site
state: New York
city: Austin
country: United States
facility: Clinical Site
state: Texas
city: Burgas
country: Bulgaria
facility: Clinical Site
city: Kazanlak
country: Bulgaria
facility: Clinical Site
city: Pleven
country: Bulgaria
facility: Clinical Site
city: Ruse
country: Bulgaria
facility: Clinical Site
city: Tsarev Brod
country: Bulgaria
facility: Clinical Site
city: Veliko Tarnovo
country: Bulgaria
facility: Clinical Site
city: Veliko Tarnovo
country: Bulgaria
facility: Clinical Site
city: Vratsa
country: Bulgaria
facility: Clinical Site
city: Brno
country: Czechia
facility: Clinical Site
city: Brno
country: Czechia
facility: Clinical Site
city: Ostrava
country: Czechia
facility: Clinical Site
city: Plzen
country: Czechia
facility: Clinical site
city: Prague
country: Czechia
facility: Clinical Site
city: Prague
country: Czechia
facility: Clinical Site
city: Budapest
country: Hungary
facility: Clinical Site
city: Budapest
country: Hungary
facility: Clinical Site
city: Budapest
country: Hungary
facility: Clinical Site
city: Gyöngyös
country: Hungary
facility: Clinical Site
city: Guwahati
country: India
facility: Clinical Site
state: Assam
city: Ahmedabad
country: India
facility: Clinical Site
state: Gujarat
city: Junagadh
country: India
facility: Clinical Site
state: Gujarat
city: Vadodara
country: India
facility: Clinical Site
state: Gujarat
city: Mangaluru
country: India
facility: Clinical Site
state: Karnataka
city: Mysore
country: India
facility: Clinical Site
state: Karnataka
city: Kozhikode
country: India
facility: Clinical Site
state: Kerala
city: Aurangabad
country: India
facility: Clinical Site
state: Maharashtra
city: Nagpur
country: India
facility: Clinical Site
state: Maharashtra
city: Nashik
country: India
facility: Clinical Site
state: Maharashtra
city: Nashik
country: India
facility: Clinical Site
state: Maharashtra
city: Ludhiāna
country: India
facility: Clinical Site
state: Punjab
city: Jaipur
country: India
facility: Clinical Site
state: Rajasthan
city: Lucknow
country: India
facility: Clinical Site
state: Uttar Pradesh
city: Varanasi
country: India
facility: Clinical Site
state: Uttar Pradesh
city: Bratislava
country: Slovakia
facility: Clinical Site
city: Košice
country: Slovakia
facility: Clinical Site
city: Rimavská Sobota
country: Slovakia
facility: Clinical Site
city: Svidník
country: Slovakia
facility: Clinical Site
city: Vranov Nad Topľou
country: Slovakia
facility: Clinical Site
city: Zlaté Moravce
country: Slovakia
facility: Clinical Site
Study officials:
References: