Major Depressive Disorder
Conditions
Keywords
REL-1017
Brief summary
This is an outpatient, 2-arm, Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of REL-1017 once daily (QD) as an adjunctive treatment of Major Depressive Disorder. Study participants will continue to take their current antidepressant therapy in addition to the study drug or placebo for the duration of the treatment period.
Interventions
DRUGREL-1017
REL-1017 tablet
DRUGPlacebo
Placebo tablet
Sponsors
Relmada Therapeutics, Inc.
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
* Adults 18 to 65 years, inclusive. * Diagnosed with Major Depressive Disorder (MDD) based on structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, DSM-5 (SCID-5) for MDD. * Current major depressive episode. * With inadequate response to 1-3 first-line antidepressants administered at an adequate and stable dose
Exclusion criteria
* Any current and primary psychiatric disorder other than Major Depressive Disorder. * Severe alcohol or substance use disorder. * History of bipolar I and II disorder, psychosis, and/or mania. * Acute or chronic condition that, in the Investigator's opinion, would limit the subject's ability to complete or participate in this clinical study. * Prior participation in a ketamine, esketamine, dextromethorphan or any other NMDAR- antagonist study, or received esketamine at any time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the MADRS10 Total Score From Baseline to Day 28 | Day 28 | Therapeutic efficacy of REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10) A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MADRS10 Remission Rate (Total Score ≤10) at Day 28 | Day 28 | Therapeutic remission rate with REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). Remission is defined as MADRS10 Total Score ≤10 at Day 28. A higher percentage of remission indicates a higher percentage of subjects with MADRS10 Total Score ≤10 at Day 28. |
| MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28 | Day 28 | Therapeutic response to REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). Response rate is defined as an improvement ≥50% compared with total Baseline MADRS10 score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| REL-1017 A 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 25 mg REL-1017 in addition to their ongoing antidepressant.
REL-1017: REL-1017 tablet | 113 |
| Placebo Three tablets of matching placebo will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 1 placebo tablet in addition to their ongoing antidepressant.
Placebo: Placebo tablet | 114 |
| Total | 227 |
Baseline characteristics
| Characteristic | Placebo | Total | REL-1017 |
|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 14.2 | 43.5 years STANDARD_DEVIATION 14.6 | 43.3 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 52 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 164 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 30 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 90 Participants | 175 Participants | 85 Participants |
| Sex: Female, Male Female | 87 Participants | 169 Participants | 82 Participants |
| Sex: Female, Male Male | 27 Participants | 58 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 113 | 0 / 114 |
| other Total, other adverse events | 34 / 113 | 34 / 114 |
| serious Total, serious adverse events | 3 / 113 | 0 / 114 |
Outcome results
Primary
Change in the MADRS10 Total Score From Baseline to Day 28
Therapeutic efficacy of REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10) A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement.
Time frame: Day 28
Population: Full Analysis Set: defined as all subjects who received at least one dose of study medication and were assessed for the primary efficacy endpoint at both Baseline and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 25 mg | Change in the MADRS10 Total Score From Baseline to Day 28 | -15.1 score on a scale | Standard Deviation 11.3 |
| Placebo | Change in the MADRS10 Total Score From Baseline to Day 28 | -12.9 score on a scale | Standard Deviation 10.4 |
Secondary
MADRS10 Remission Rate (Total Score ≤10) at Day 28
Therapeutic remission rate with REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). Remission is defined as MADRS10 Total Score ≤10 at Day 28. A higher percentage of remission indicates a higher percentage of subjects with MADRS10 Total Score ≤10 at Day 28.
Time frame: Day 28
Population: Full Analysis Set: defined as all subjects who received at least one dose of study medication and had the Baseline assessment of the primary efficacy endpoint performed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REL-1017 25 mg | MADRS10 Remission Rate (Total Score ≤10) at Day 28 | 22.1 percentage of participants in remission |
| Placebo | MADRS10 Remission Rate (Total Score ≤10) at Day 28 | 13.2 percentage of participants in remission |
Secondary
MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28
Therapeutic response to REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). Response rate is defined as an improvement ≥50% compared with total Baseline MADRS10 score.
Time frame: Day 28
Population: Full Analysis Set: defined as all subjects who received at least one dose of study medication and had the Baseline assessment of the primary efficacy endpoint performed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REL-1017 25 mg | MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28 | 39.8 percentage of responders |
| Placebo | MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28 | 27.2 percentage of responders |