Depressive Disorder, Major
Conditions
Keywords
Depression
Brief summary
The study will evaluate the efficacy, safety, and tolerability of 450 milligrams (mg) or 225 mg of Rapastinel compared to placebo in the prevention of relapse in participants with major depressive disorder (MDD).
Interventions
DRUGRapastinel
Rapastinel 450 mg or 225 mg (prefilled syringe, weekly intravenous IV administration) or Rapastinel 450 mg or 225 mg (prefilled syringe, clinically driven schedule IV administration, variable interval, placebo on intervening weeks)
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
- * Completion of Study RAP-MD-30, RAP-MD-31, or RAP-MD-32 * 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 |
|---|---|---|
| Time to First Relapse During the 52 Weeks of the Double-Blind Treatment Period (DBTP) | 52 Weeks | The time in days to first relapse is defined as the number of days from the date of randomization to the first relapse. |
Countries
Hungary, Japan, Poland, Slovakia, United States
Participant flow
Recruitment details
Patients from RAP-MD-33 completed one of the rapastinel lead-in studies - RAP-MD-30, RAP-MD-31, or RAP-MD-32.
Pre-assignment details
363 patients enrolled in the Open Label Treatment Period (OLTP). Of these, 209 completed OLTP and 137 entered Double Blind Treatment Period (DBTP) and were randomized. Patients who completed or discontinued from the study can enter a 2-wk safety follow-up period (SFUP). 165 patients from OLTP and 91 patients from DBTP entered the SFUP.
Participants by arm
| Arm | Count |
|---|---|
| DBTP Placebo Weekly Placebo (prefilled syringe, weekly IV administration) | 40 |
| DBTP Rapastinel Clinically Driven Schedule Rapastinel 450 mg or 225 mg (prefilled syringe, clinically driven schedule IV administration, variable interval, placebo on intervening weeks) | 42 |
| DBTP Rapastinel Weekly Rapastinel 450 mg or 225 mg (prefilled syringe, weekly intravenous IV administration) | 55 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Treatment Period (DBTP) | Adverse Event | 0 | 2 | 0 | 1 |
| Double-Blind Treatment Period (DBTP) | Lost to Follow-up | 0 | 0 | 3 | 4 |
| Double-Blind Treatment Period (DBTP) | Miscellaneous Reasons | 0 | 1 | 0 | 0 |
| Double-Blind Treatment Period (DBTP) | Protocol Violation | 0 | 1 | 1 | 1 |
| Double-Blind Treatment Period (DBTP) | Study terminated by sponsor | 0 | 22 | 26 | 38 |
| Double-Blind Treatment Period (DBTP) | Withdrawal by Subject | 0 | 4 | 1 | 1 |
| Open-Label Treatment Period | Adverse Event | 7 | 0 | 0 | 0 |
| Open-Label Treatment Period | Lack of Efficacy | 18 | 0 | 0 | 0 |
| Open-Label Treatment Period | Lost to Follow-up | 10 | 0 | 0 | 0 |
| Open-Label Treatment Period | Non-compliance with study drug | 1 | 0 | 0 | 0 |
| Open-Label Treatment Period | Protocol-specified withdrawal met | 6 | 0 | 0 | 0 |
| Open-Label Treatment Period | Protocol Violation | 2 | 0 | 0 | 0 |
| Open-Label Treatment Period | Study terminated by sponsor | 74 | 0 | 0 | 0 |
| Open-Label Treatment Period | Withdrawal by Subject | 36 | 0 | 0 | 0 |
| Safety Follow-Up Period | Lost to Follow-up | 1 | 0 | 0 | 1 |
| Safety Follow-Up Period | Miscellaneous Reasons | 2 | 0 | 0 | 0 |
| Safety Follow-Up Period | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | DBTP Placebo Weekly | DBTP Rapastinel Clinically Driven Schedule | DBTP Rapastinel Weekly | Total |
|---|---|---|---|---|
| Age, Continuous | 47 Years STANDARD_DEVIATION 13.95 | 43.6 Years STANDARD_DEVIATION 12.57 | 43.9 Years STANDARD_DEVIATION 11.66 | 44.7 Years STANDARD_DEVIATION 12.63 |
| BMI | 29.89 kg/m^2 STANDARD_DEVIATION 5.686 | 30.95 kg/m^2 STANDARD_DEVIATION 7.289 | 31.15 kg/m^2 STANDARD_DEVIATION 6.279 | 30.72 kg/m^2 STANDARD_DEVIATION 6.421 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 8 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 34 Participants | 46 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 168.31 cm STANDARD_DEVIATION 8.996 | 166.92 cm STANDARD_DEVIATION 9.858 | 168.47 cm STANDARD_DEVIATION 9.196 | 167.95 cm STANDARD_DEVIATION 9.304 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 5 Participants | 11 Participants | 24 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 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 33 Participants | 42 Participants | 102 Participants |
| Sex: Female, Male Female | 30 Participants | 29 Participants | 44 Participants | 103 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 11 Participants | 34 Participants |
| Weight | 84.84 kg STANDARD_DEVIATION 17.86 | 85.88 kg STANDARD_DEVIATION 19.21 | 88.53 kg STANDARD_DEVIATION 19.24 | 86.64 kg STANDARD_DEVIATION 18.77 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 363 | 0 / 40 | 0 / 42 | 0 / 55 |
| other Total, other adverse events | 44 / 363 | 17 / 40 | 9 / 42 | 13 / 55 |
| serious Total, serious adverse events | 4 / 363 | 1 / 40 | 1 / 42 | 0 / 55 |
Outcome results
Primary
Time to First Relapse During the 52 Weeks of the Double-Blind Treatment Period (DBTP)
The time in days to first relapse is defined as the number of days from the date of randomization to the first relapse.
Time frame: 52 Weeks
Population: The Double-blind Safety Population consisted of all patients in the Open-label Safety Population who were randomized to a treatment group during the DBTP of the study and received at least 1 dose of double-blind IP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBTP Placebo Weekly | Time to First Relapse During the 52 Weeks of the Double-Blind Treatment Period (DBTP) | NA Days |
| DBTP Rapastinel Clinically Driven Schedule | Time to First Relapse During the 52 Weeks of the Double-Blind Treatment Period (DBTP) | 203 Days |
| DBTP Rapastinel Weekly | Time to First Relapse During the 52 Weeks of the Double-Blind Treatment Period (DBTP) | NA Days |