Depressive Disorder, Major
Conditions
Keywords
Depression
Brief summary
The study will evaluate the efficacy, safety, and tolerability of 225 milligrams (mg) and 450 milligrams (mg) of Rapastinel, compared to placebo in participants with major depressive disorder (MDD).
Interventions
DRUGRapastinel
Rapastinel (prefilled syringe, weekly intravenous IV administration).
DRUGPlacebo
Placebo (prefilled syringe, weekly IV administration).
Sponsors
Naurex, Inc, an affiliate of Allergan plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD * Current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1 * Treatment naive in the current episode or have inadequate response to 1-3 antidepressant therapies given at adequate dose and duration in the current episode * If female of childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test
Exclusion criteria
* DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1 * Lifetime history of meeting DSM-5 criteria for: 1. Schizophrenia spectrum or other psychotic disorder 2. Bipolar or related disorder 3. Major neurocognitive disorder 4. Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study 5. Dissociative disorder 6. Posttraumatic stress disorder 7. MDD with psychotic features * Significant suicide risk, as judged by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Treatment (End of Week 6). | Baseline to end of Week 6 | The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MADRS Total Score at 1 Day After First Dose of Treatment | Baseline to 1 Day post-first dose | The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement. |
Countries
Hungary, Japan, Poland, Russia, Slovakia
Participant flow
Pre-assignment details
Total of 68 participants were screened for eligibility; 50 participants randomized to receive double-blind treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (prefilled syringe, weekly IV administration). | 15 |
| Rapastinel 225mg Rapastinel (prefilled syringe, weekly intravenous IV administration). | 17 |
| Rapastinel 450mg Rapastinel (prefilled syringe, weekly intravenous IV administration). | 18 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double Blind Treatment Period | Lack of Efficacy | 1 | 0 | 0 |
| Double Blind Treatment Period | Study Terminated by Sponsor | 5 | 6 | 8 |
Baseline characteristics
| Characteristic | Placebo | Rapastinel 225mg | Rapastinel 450mg | Total |
|---|---|---|---|---|
| Age, Continuous | 42.4 Years STANDARD_DEVIATION 10.36 | 44.7 Years STANDARD_DEVIATION 10.83 | 43.2 Years STANDARD_DEVIATION 11.06 | 43.5 Years STANDARD_DEVIATION 10.6 |
| BMI | 25.83 kg/m^2 STANDARD_DEVIATION 4.41 | 25.85 kg/m^2 STANDARD_DEVIATION 5.5 | 24.82 kg/m^2 STANDARD_DEVIATION 5.09 | 25.47 kg/m^2 STANDARD_DEVIATION 4.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 17 Participants | 18 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 169.27 cm STANDARD_DEVIATION 10.68 | 163.77 cm STANDARD_DEVIATION 5.9 | 168.04 cm STANDARD_DEVIATION 6.36 | 166.96 cm STANDARD_DEVIATION 7.97 |
| Montgomery-Asberg Depression Rating Scale (MADRS) total score at baseline | 34.5 Score on a scale STANDARD_DEVIATION 4.34 | 35.2 Score on a scale STANDARD_DEVIATION 4.78 | 34.8 Score on a scale STANDARD_DEVIATION 4.72 | 34.9 Score on a scale STANDARD_DEVIATION 4.54 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 7 Participants | 9 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 10 Participants | 9 Participants | 26 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 7 Participants | 27 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 11 Participants | 23 Participants |
| Weight | 73.86 kg STANDARD_DEVIATION 13.14 | 69.58 kg STANDARD_DEVIATION 16.52 | 70.32 kg STANDARD_DEVIATION 15.72 | 71.13 kg STANDARD_DEVIATION 15.09 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 17 | 0 / 18 |
| other Total, other adverse events | 6 / 15 | 1 / 17 | 6 / 18 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 | 0 / 18 |
Outcome results
Primary
Change From Baseline on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Treatment (End of Week 6).
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Time frame: Baseline to end of Week 6
Population: The Modified Intent-to-Treat (mITT) Population consisted of all patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Treatment (End of Week 6). | -11.3 Score on a scale | Standard Deviation 9.06 |
| Rapastinel 225mg | Change From Baseline on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Treatment (End of Week 6). | -21.3 Score on a scale | Standard Deviation 10.31 |
| Rapastinel 450mg | Change From Baseline on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Treatment (End of Week 6). | -12.9 Score on a scale | Standard Deviation 11.36 |
Secondary
Change From Baseline in MADRS Total Score at 1 Day After First Dose of Treatment
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Time frame: Baseline to 1 Day post-first dose
Population: The Modified Intent-to-Treat (mITT) Population consists of all patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in MADRS Total Score at 1 Day After First Dose of Treatment | -6.7 Score on a scale | Standard Deviation 5.36 |
| Rapastinel 225mg | Change From Baseline in MADRS Total Score at 1 Day After First Dose of Treatment | -7.4 Score on a scale | Standard Deviation 9.1 |
| Rapastinel 450mg | Change From Baseline in MADRS Total Score at 1 Day After First Dose of Treatment | -6.4 Score on a scale | Standard Deviation 9.11 |