Depressive Disorder, Major
Conditions
Brief summary
This study will evaluate the long-term safety and tolerability of rapastinel as an adjunctive to antidepressant therapy (ADT) in patients with major depressive disorder (MDD).
Interventions
DRUGRapastinel
Rapastinel pre-filled syringes for IV injections.
Sponsors
Naurex, Inc, an affiliate of Allergan plc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 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 Screening * Have no more than partial response (\< 50% improvement) to ongoing treatment with a protocol-allowed antidepressant * 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 Screening * Lifetime history of meeting DSM-5 criteria for: * Schizophrenia spectrum or other psychotic disorder * Bipolar or related disorder * Major neurocognitive disorder * 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 * Dissociative disorder * Posttraumatic stress disorder * MDD with psychotic features * Significant suicide risk, as judged by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 52 Weeks | An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brief Psychiatric Rating Scale Positive Symptoms Subscale (BPRS+) | Baseline to 52 Weeks | The BPRS+ is a subset of the BPRS that assesses 4 components of the BPRS+ related to the degree of psychosis: Conceptual Disorganization, Suspiciousness, Hallucinatory Behavior, and Unusual Thought Content assessed by the investigator using a 7-point scale ranging from 1=Not Present to 7=Extremely Severe for a total possible score of 0 (best) to 28 (worst). A negative change from Baseline indicates improvement. |
| Change From Baseline in the Clinician Administered Dissociative States Scale (CADSS) | Baseline to 52 Weeks | The Clinician Administered Dissociative States Scale (CADSS) is a clinician-administered measure of perceptual, behavioral, and attentional alterations occurring during active dissociative experiences composed of 23 subjective self-reported and 5 objective observer-reported ratings, each scored from 0 (not at all) to 4 (extremely). Only the 23 subjective items will be collected and analyzed. The sum of each of the 23 subjective items was used for a total score of 0-92. A negative change from Baseline indicates improvement. |
Countries
United States
Participant flow
Recruitment details
The study was planned to be terminated when 100 patients had completed the 52-week Open Label Treatment Period (OLTP).
Pre-assignment details
Patients who either completed the RAP-MD-04 Double-blind Treatment Period (DBTP) or who did not meet criteria to be randomized into the DBTP of RAP-MD-04 and were therefore discontinued from that study were eligible for Study RAP-MD-06.
Participants by arm
| Arm | Count |
|---|---|
| Rapastinel Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks. | 617 |
| Total | 617 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 23 |
| Overall Study | Lack of Efficacy | 20 |
| Overall Study | Lost to Follow-up | 21 |
| Overall Study | Miscellaneous Reasons | 10 |
| Overall Study | Non-compliance w/Background ADT | 1 |
| Overall Study | Non-compliance with Study Drug | 4 |
| Overall Study | Pregnancy | 4 |
| Overall Study | Protocol Violation | 21 |
| Overall Study | Site Terminated by Sponsor | 5 |
| Overall Study | Study Terminated by Sponsor | 257 |
| Overall Study | Withdrawal by Subject | 72 |
Baseline characteristics
| Characteristic | Rapastinel |
|---|---|
| Age, Continuous | 46.5 Years STANDARD_DEVIATION 11.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 83 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 534 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 107 Participants |
| Race/Ethnicity, Customized Multiple | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 4 Participants |
| Race/Ethnicity, Customized White | 485 Participants |
| Sex: Female, Male Female | 455 Participants |
| Sex: Female, Male Male | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 617 |
| other Total, other adverse events | 285 / 617 |
| serious Total, serious adverse events | 28 / 617 |
Outcome results
Primary
The Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: 52 Weeks
Population: The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rapastinel | The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 457 Count of Participants |
Secondary
Change From Baseline in Brief Psychiatric Rating Scale Positive Symptoms Subscale (BPRS+)
The BPRS+ is a subset of the BPRS that assesses 4 components of the BPRS+ related to the degree of psychosis: Conceptual Disorganization, Suspiciousness, Hallucinatory Behavior, and Unusual Thought Content assessed by the investigator using a 7-point scale ranging from 1=Not Present to 7=Extremely Severe for a total possible score of 0 (best) to 28 (worst). A negative change from Baseline indicates improvement.
Time frame: Baseline to 52 Weeks
Population: The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rapastinel | Change From Baseline in Brief Psychiatric Rating Scale Positive Symptoms Subscale (BPRS+) | -0.0 Scores on a scale | Standard Deviation 0.33 |
Secondary
Change From Baseline in the Clinician Administered Dissociative States Scale (CADSS)
The Clinician Administered Dissociative States Scale (CADSS) is a clinician-administered measure of perceptual, behavioral, and attentional alterations occurring during active dissociative experiences composed of 23 subjective self-reported and 5 objective observer-reported ratings, each scored from 0 (not at all) to 4 (extremely). Only the 23 subjective items will be collected and analyzed. The sum of each of the 23 subjective items was used for a total score of 0-92. A negative change from Baseline indicates improvement.
Time frame: Baseline to 52 Weeks
Population: The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rapastinel | Change From Baseline in the Clinician Administered Dissociative States Scale (CADSS) | -0.2 Scores on a Scale | Standard Deviation 1.24 |