A Study to Assess the Efficacy and Safety of REL-1017 as Monotherapy for Major Depressive Disorder (MDD)

• REL-1017 (Drug), also known as esmethadone: REL-1017 tablet
• Placebo (Drug): Placebo tablet

Primary outcomes

• Change in the MADRS10 Total Score From Baseline to Day 28 [Day 28]: Therapeutic efficacy of REL-1017 as monotherapy 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 outcomes

• 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

Sex: All, ages: 18 Years to 65 Years

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.

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.

Participant flow

Outcome results

• Change in the MADRS10 Total Score From Baseline to Day 28 (Primary), Mean, score on a scale: REL-1017 25 mg -14.8 +/- 12.4; Placebo -13.9 +/- 10.8
• MADRS10 Remission Rate (Total Score ≤10) at Day 28 (Secondary), Number, percentage of participants in remission: REL-1017 25 mg 21.6 (15.0 to 29.9); Placebo 16.4 (10.7 to 24.2)
• MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28 (Secondary), Number, percentage of responders: REL-1017 25 mg 38.8 (30.4 to 47.9); Placebo 34.5 (26.5 to 43.5)

Adverse events

Time frame: TEAE that starts or worsens at any time after initiation of study drug collected up to 14 days post treatment (Day 42).

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2022-08-03)

• Marco Pappagallo, MD, Study director, Relmada Therapeutics