Major Depressive Disorder
Conditions
Keywords
Adjunctive MDD Therapy
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.
Interventions
DRUGLumateperone
Lumateperone 42 mg capsules administered orally, once daily.
DRUGPlacebo
Matching capsules administered orally, once daily.
Sponsors
Intra-Cellular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Åsberg Depression Rating Scale | Day 43 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression Scale-Severity | Day 43 | Change from baseline to Day 43 in the Clinical Global Impression Scale-Severity (CGI-S). 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). |
Countries
Bulgaria, Czechia, Hungary, India, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone 42 mg Lumateperone: Lumateperone 42 mg capsules administered orally, once daily. | 241 |
| Placebo Placebo: Matching capsules administered orally, once daily. | 243 |
| Total | 484 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 2 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Lumateperone 42 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 12.39 | 45.0 years STANDARD_DEVIATION 12.43 | 45.1 years STANDARD_DEVIATION 12.51 |
| Montgomery Asberg Depression Rating Scale (MADRS) | 30.4 units on a scale STANDARD_DEVIATION 3.76 | 30.2 units on a scale STANDARD_DEVIATION 3.64 | 30.0 units on a scale STANDARD_DEVIATION 3.51 |
| Race/Ethnicity, Customized Asian | 40 Participants | 73 Participants | 33 Participants |
| Race/Ethnicity, Customized Black or African American | 20 Participants | 36 Participants | 16 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 180 Participants | 371 Participants | 191 Participants |
| Region of Enrollment Bulgaria | 54 participants | 109 participants | 55 participants |
| Region of Enrollment Czechia | 51 participants | 105 participants | 54 participants |
| Region of Enrollment Hungary | 6 participants | 16 participants | 10 participants |
| Region of Enrollment India | 34 participants | 65 participants | 31 participants |
| Region of Enrollment Slovakia | 21 participants | 39 participants | 18 participants |
| Region of Enrollment United States | 75 participants | 150 participants | 75 participants |
| Sex: Female, Male Female | 158 Participants | 318 Participants | 160 Participants |
| Sex: Female, Male Male | 83 Participants | 166 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 241 | 0 / 243 |
| other Total, other adverse events | 92 / 241 | 53 / 243 |
| serious Total, serious adverse events | 1 / 241 | 1 / 243 |
Outcome results
Primary
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.
Time frame: Day 43
Population: The analysis of the primary and secondary efficacy outcome measures are based on the Modified Intent-to-Treat (mITT) Population which included 481 randomized patients. The mITT Population includes all randomized patients who received at least 1 dose of study drug, had a baseline MADRS total score, and who had at least one on-study drug, postbaseline MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42 mg | Montgomery-Åsberg Depression Rating Scale | -14.7 score on a scale | Standard Error 0.54 |
| Placebo | Montgomery-Åsberg Depression Rating Scale | -9.8 score on a scale | Standard Error 0.53 |
p-value: <0.000195% CI: [-6.38, -3.44]Mixed Effects Model for Repeated Measure
Secondary
Clinical Global Impression Scale-Severity
Change from baseline to Day 43 in the Clinical Global Impression Scale-Severity (CGI-S). 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).
Time frame: Day 43
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42 mg | Clinical Global Impression Scale-Severity | -1.6 score on a scale | Standard Error 0.07 |
| Placebo | Clinical Global Impression Scale-Severity | -0.9 score on a scale | Standard Error 0.07 |
p-value: <0.000195% CI: [-0.85, -0.48]Mixed Effects Model for Repeated Measure