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CompletedNCT04688164Reliance IUpdated Aug 27, 2024Results posted

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

A Phase 3 interventional study of REL-1017 and Placebo in Major Depressive Disorder, sponsored by Relmada Therapeutics, Inc.. Completed at 11 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-08-27.

Sponsored by Relmada Therapeutics, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
227
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Major Depressive Disorder

Keywords

  • REL-1017
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
227 participants (actual)

Study arms

  • Experimental
    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.

    Drug: REL-1017

  • Placebo comparator
    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.

    Drug: Placebo

Interventions

  • DrugREL-1017

    REL-1017 tablet

    Also known as: esmethadone

  • DrugPlacebo

    Placebo tablet

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

06

Results

Posted Mar 26, 2024

Participant flow

Participant flow — Overall Study
MilestoneREL-1017Placebo
Started113114
Completed10699
Not completed715

Outcome measures

PrimaryChange 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
Reported as:
Mean · score on a scale
Change in the MADRS10 Total Score From Baseline to Day 28
score on a scaleREL-1017 25 mgPlacebo
Change in the MADRS10 Total Score From Baseline to Day 28-15.1 ± 11.3-12.9 ± 10.4
SecondaryMADRS10 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
Reported as:
Number · percentage of participants in remission
MADRS10 Remission Rate (Total Score ≤10) at Day 28
percentage of participants in remissionREL-1017 25 mgPlacebo
MADRS10 Remission Rate (Total Score ≤10) at Day 2822.1 (15.5 to 30.6)13.2 (8.1 to 20.6)
SecondaryMADRS10 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
Reported as:
Number · percentage of responders
MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28
percentage of respondersREL-1017 25 mgPlacebo
MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 2839.8 (31.3 to 49.0)27.2 (19.9 to 36.0)

Adverse events

Collected over TEAE that starts or worsens at any time after initiation of study drug collected up to 14 days post treatment (Day 42).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
REL-1017 25 mg0/113 (0%)3/113 (2.7%)34/113 (30.1%)
Placebo0/114 (0%)0/114 (0%)34/114 (29.8%)
Most frequent serious events
Most frequent serious events
EventREL-1017 25 mgPlacebo
Suicidal IdeationPsychiatric disorders2/1130/114
CholecystitisHepatobiliary disorders1/1130/114
Most frequent other events
Most frequent other events
EventREL-1017 25 mgPlacebo
HeadacheNervous system disorders13/1139/114
COVID-19Infections and infestations6/11310/114
Upper respiratory tract infectionInfections and infestations8/1136/114
NauseaGastrointestinal disorders8/1135/114
DizzinessNervous system disorders7/1132/114
DiarrhoeaGastrointestinal disorders5/1137/114
ConstipationGastrointestinal disorders3/1137/114

Baseline characteristics

Age, Continuous
Age, Continuous(years)REL-1017PlaceboTotal
Mean43.3 ± 15.143.6 ± 14.243.5 ± 14.6
Sex: Female, Male
Sex: Female, Male(Participants)REL-1017PlaceboTotal
Female8287169
Male312758
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)REL-1017PlaceboTotal
Hispanic or Latino292352
Not Hispanic or Latino7985164
Unknown or Not Reported5611
Race (NIH/OMB)
Race (NIH/OMB)(Participants)REL-1017PlaceboTotal
American Indian or Alaska Native000
Asian6713
Native Hawaiian or Other Pacific Islander000
Black or African American161430
White8590175
More than one race426
Unknown or Not Reported213
07

Study locations

11 sites
  • Relmada Site
    Miami Springs, Florida 33166, United States
  • Relmada Site
    Miami, Florida 33175, United States
  • Relmada Site
    Palm Bay, Florida 32905, United States
  • Relmada Site
    Decatur, Georgia 30030, United States
  • Relmada Site
    Chicago, Illinois 60634, United States
  • Relmada Site
    Boston, Massachusetts 02116, United States
  • Relmada Site
    Watertown, Massachusetts 02472, United States
  • Relmada Site
    O'Fallon, Missouri 63368, United States
  • Relmada Site
    New York, New York 10128, United States
  • Relmada Site
    Cincinnati, Ohio 45215, United States
  • Relmada Site
    Austin, Texas 78737, United States
08

References and documents

Publications

  • Fava M, Stahl SM, Pani L, De Martin S, Cutler AJ, Maletic V, Gorodetzky CW, Vocci FJ, Sapienza FL, Kosten TR, Kroger C, Champasa P, O'Gorman C, Guidetti C, Alimonti A, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M. Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial. J Clin Psychiatry. 2024 Jun 17;85(3):24m15265. doi: 10.4088/JCP.24m15265. PubMed 38917366 ↗

Related links

Study documents

  • Protocol and statistical analysis plan · Dec 1, 2022

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04688164
Lead sponsor
Relmada Therapeutics, Inc.
Responsible party
Sponsor
First posted
Dec 29, 2020
Start date
Jan 8, 2021
Primary completion
Nov 1, 2022
Completion
Nov 10, 2022
Results posted
Mar 26, 2024
Last update
Aug 27, 2024

Study contacts

Marco Pappagallo, MD
study director · Relmada Therapeutics

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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