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 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.
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. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor-approved rater using the MINI 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 (Visit 1) 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. 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. 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-Asberg 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
Argentina, Bulgaria, Finland, Germany, Poland, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone 42 mg Lumateperone: Lumateperone 42 mg capsules administered orally, once daily. | 242 |
| Placebo Placebo: Matching capsules administered orally, once daily. | 238 |
| Total | 480 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 29 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 9 |
Baseline characteristics
| Characteristic | Placebo | Total | Lumateperone 42 mg |
|---|---|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 12.16 | 46.0 years STANDARD_DEVIATION 12.47 | 45.6 years STANDARD_DEVIATION 12.79 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 31.5 units on a scale STANDARD_DEVIATION 3.98 | 31.1 units on a scale STANDARD_DEVIATION 3.94 | 30.8 units on a scale STANDARD_DEVIATION 3.87 |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 14 Participants | 6 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 223 Participants | 458 Participants | 235 Participants |
| Region of Enrollment Argentina | 30 participants | 61 participants | 31 participants |
| Region of Enrollment Bulgaria | 35 participants | 68 participants | 33 participants |
| Region of Enrollment Germany | 18 participants | 34 participants | 16 participants |
| Region of Enrollment Poland | 78 participants | 161 participants | 83 participants |
| Region of Enrollment Sweden | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 76 participants | 154 participants | 78 participants |
| Sex: Female, Male Female | 165 Participants | 334 Participants | 169 Participants |
| Sex: Female, Male Male | 73 Participants | 146 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 242 | 0 / 238 |
| other Total, other adverse events | 138 / 242 | 54 / 238 |
| serious Total, serious adverse events | 2 / 242 | 0 / 238 |
Outcome results
Primary
Montgomery-Asberg 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 469 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-Asberg Depression Rating Scale | -14.7 units on a scale | Standard Error 0.56 |
| Placebo | Montgomery-Asberg Depression Rating Scale | -10.2 units on a scale | Standard Error 0.54 |
p-value: <0.000195% CI: [-6.03, -3.02]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 | -1.5 units on a scale | Standard Error 0.07 |
| Placebo | Clinical Global Impression Scale-Severity | -1.0 units on a scale | Standard Error 0.07 |
p-value: <0.000195% CI: [-0.72, -0.33]Mixed Effects Model for Repeated Measure