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NCT04688164: Reliance I

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

Completed Phase 3 Results posted Last updated 27 August 2024
What this trial tests

Phase 3 trial testing REL-1017 in Major Depressive Disorder in 227 participants. Completed in 10 November 2022.

Timeline
8 January 2021
Primary endpoint
1 November 2022
10 November 2022

Quick facts

Lead sponsorRelmada Therapeutics, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment227
Start date8 January 2021
Primary completion1 November 2022
Estimated completion10 November 2022
Sites11 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Relmada Therapeutics, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with Major Depressive Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in the MADRS10 Total Score From Baseline to Day 28 Primary · 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.

GroupValue95% CI
REL-1017 25 mg-15.1± 11.3
Placebo-12.9± 10.4
MADRS10 Remission Rate (Total Score ≤10) at Day 28 Secondary · 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.

GroupValue95% CI
REL-1017 25 mg22.115.5 – 30.6
Placebo13.28.1 – 20.6
MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28 Secondary · 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.

GroupValue95% CI
REL-1017 25 mg39.831.3 – 49.0
Placebo27.219.9 – 36.0

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAE that starts or worsens at any time after initiation of study drug collected up to 14 days post treatment (Day 42).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

REL-1017 25 mg
Serious: 3/113 (3%)
Deaths: 0/113
Placebo
Serious: 0/114 (0%)
Deaths: 0/114

Serious adverse events (2 terms)

ReactionSystemREL-1017 25 mgPlacebo
Suicidal IdeationPsychiatric disorders
CholecystitisHepatobiliary disorders
Other adverse events (7 terms — click to expand)

ReactionSystemREL-1017 25 mgPlacebo
HeadacheNervous system disorders
COVID-19Infections and infestations
Upper respiratory tract infectionInfections and infestations
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
ConstipationGastrointestinal disorders
DizzinessNervous system disorders

Most-reported serious reactions: Suicidal Ideation, Cholecystitis.

Data from ClinicalTrials.gov NCT04688164 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status.
    Henter ID, Park LT, Zarate CA. · · 2021 · cited 104× · PMID 33904154 · DOI 10.1007/s40263-021-00816-x
  2. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
    Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
  3. Clinical specificity profile for novel rapid acting antidepressant drugs.
    Scala M, Fanelli G, De Ronchi D, Serretti A, et al · · 2023 · cited 33× · PMID 37381161 · DOI 10.1097/yic.0000000000000488
  4. Glutamatergic Modulators for Major Depression from Theory to Clinical Use.
    McIntyre RS, Jain R. · · 2024 · cited 31× · PMID 39150594 · DOI 10.1007/s40263-024-01114-y
  5. Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.
    Seillier C, Lesept F, Toutirais O, Potzeha F, et al · · 2022 · cited 26× · PMID 36142247 · DOI 10.3390/ijms231810336
  6. Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression.
    Vecera CM, C Courtes A, Jones G, Soares JC, et al · · 2023 · cited 23× · PMID 38004437 · DOI 10.3390/ph16111572
  7. Pharmacological Comparative Characterization of REL-1017 (Esmethadone-HCl) and Other NMDAR Channel Blockers in Human Heterodimeric N-Methyl-D-Aspartate Receptors.
    Bettini E, Stahl SM, De Martin S, Mattarei A, et al · · 2022 · cited 23× · PMID 36015145 · DOI 10.3390/ph15080997
  8. REL-1017 (esmethadone; D-methadone) does not cause reinforcing effect, physical dependence and withdrawal signs in Sprague Dawley rats.
    Henningfield J, Gauvin D, Bifari F, Fant R, et al · · 2022 · cited 13× · PMID 35794162 · DOI 10.1038/s41598-022-15055-3

Verify or expand the search:

Other trials of REL-1017

Trials testing the same drug.

Other recruiting trials for Major Depressive Disorder

Currently open trials in the same condition.

Other Relmada Therapeutics, Inc. trials

Trials by the same sponsor.

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