Depressive Disorder, Major
Conditions
Brief summary
The study will evaluate the efficacy, safety, and tolerability of 450 milligrams (mg) of Rapastinel, compared to placebo in adult patients with major depressive disorder (MDD) who are at imminent risk of suicide.
Interventions
DRUGRapastinel
Rapastinel pre-filled syringes for weekly IV injections.
DRUGPlacebo
Placebo-matching rapastinel pre-filled syringes for weekly IV injections.
Sponsors
Naurex, Inc, an affiliate of Allergan plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 4 weeks and not exceeding 24 months in duration at visit 1 * Have current, ongoing suicidality (ideation or behavior) of sufficient severity to warrant hospitalization based on the judgment of the investigator * 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 1 month before Visit 1. * Lifetime history or currently meet 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 homicidal ideation or at imminent risk of injuring others or causing significant damage to property, as judged by the investigator. * Prior participation in any investigational study of rapastinel/GLYX-13
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline and 1 Day | 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. |
| Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score | Baseline and 1 Day | The S-STS is a patient-report informed, clinician-rated scale used to rate the severity of suicidal impulses, thoughts, and behaviors. This is a 14 item scale ranging from 0=Not at all to 4= Extremely. The total score ranges from 0 to 56 with a higher score indicating higher suicidal tendency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline and 28 Days | 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. |
| Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score | Baseline and 28 Days | The S-STS is a patient-report informed, clinician-rated scale used to rate the severity of suicidal impulses, thoughts, and behaviors. This is a 14 item scale ranging from 0=Not at all to 4= Extremely. The total score ranges from 0 to 56 with a higher score indicating higher suicidal tendency. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo-matching rapastinel weekly IV injections. | 64 |
| Rapastinel 450mg Rapastinel 450 milligram (mg) weekly intravenous (IV) injections. | 72 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 9 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 6 |
| Overall Study | Miscellaneous Reasons | 1 | 2 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 2 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 14 |
Baseline characteristics
| Characteristic | Rapastinel 450mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.3 Years STANDARD_DEVIATION 12.89 | 42.1 Years STANDARD_DEVIATION 13.45 | 42.2 Years STANDARD_DEVIATION 13.11 |
| BMI | 28.79 kg/m^2 STANDARD_DEVIATION 6.34 | 28.88 kg/m^2 STANDARD_DEVIATION 6.75 | 28.83 kg/m^2 STANDARD_DEVIATION 6.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 55 Participants | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 169.56 cm STANDARD_DEVIATION 9.86 | 172 cm STANDARD_DEVIATION 8.84 | 170.71 cm STANDARD_DEVIATION 9.44 |
| Montgomery-Asberg Depression Rating Scale (MADRS) total score at baseline | 39.8 Scores on a scale STANDARD_DEVIATION 6.04 | 40.4 Scores on a scale STANDARD_DEVIATION 5.83 | 40.0 Scores on a scale STANDARD_DEVIATION 5.93 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 33 Participants | 57 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 30 Participants | 75 Participants |
| Sex: Female, Male Female | 29 Participants | 29 Participants | 58 Participants |
| Sex: Female, Male Male | 43 Participants | 35 Participants | 78 Participants |
| Sheehan - Suicidality Tracking Scale (S-STS) Total Score (Patient-rated) | 29.6 Scores on a scale STANDARD_DEVIATION 10.45 | 30.9 Scores on a scale STANDARD_DEVIATION 10.94 | 30.2 Scores on a scale STANDARD_DEVIATION 10.67 |
| S-STS Total Score (Clinician-rated) | 28.9 Scores on a scale STANDARD_DEVIATION 9.62 | 30.0 Scores on a scale STANDARD_DEVIATION 10.22 | 29.4 Scores on a scale STANDARD_DEVIATION 9.88 |
| Weight | 82.57 kg STANDARD_DEVIATION 17.59 | 85.26 kg STANDARD_DEVIATION 19.8 | 83.83 kg STANDARD_DEVIATION 18.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 72 |
| other Total, other adverse events | 18 / 64 | 21 / 72 |
| serious Total, serious adverse events | 5 / 64 | 12 / 72 |
Outcome results
Primary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
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 and 1 Day
Population: The modified Intent-to-Treat (mITT) Population consists of all participants in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score or S-STS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -17.6 Scores on a scale | Standard Deviation 12.49 |
| Rapastinel 450mg | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -16.3 Scores on a scale | Standard Deviation 11.36 |
Primary
Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score
The S-STS is a patient-report informed, clinician-rated scale used to rate the severity of suicidal impulses, thoughts, and behaviors. This is a 14 item scale ranging from 0=Not at all to 4= Extremely. The total score ranges from 0 to 56 with a higher score indicating higher suicidal tendency.
Time frame: Baseline and 1 Day
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 or S-STS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score | -20.6 Scores on a scale | Standard Deviation 12.27 |
| Rapastinel 450mg | Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score | -20.2 Scores on a scale | Standard Deviation 11.93 |
Secondary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
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 and 28 Days
Population: The modified Intent-to-Treat (mITT) Population consists of all participants in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score or S-STS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -25.6 Scores on a scale | Standard Deviation 14.74 |
| Rapastinel 450mg | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -23.0 Scores on a scale | Standard Deviation 15 |
Secondary
Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score
The S-STS is a patient-report informed, clinician-rated scale used to rate the severity of suicidal impulses, thoughts, and behaviors. This is a 14 item scale ranging from 0=Not at all to 4= Extremely. The total score ranges from 0 to 56 with a higher score indicating higher suicidal tendency.
Time frame: Baseline and 28 Days
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 or S-STS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score | -25.9 Scores on a scale | Standard Deviation 11.61 |
| Rapastinel 450mg | Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score | -26.4 Scores on a scale | Standard Deviation 12.74 |