NCT04855747 (RELIANCE-II) is a Phase 3 clinical trial of REL-1017 in Major Depressive Disorder, sponsored by Levomecor Inc..

Who is sponsoring NCT04855747?

NCT04855747 is sponsored by Levomecor Inc..

What drugs are being tested in NCT04855747?

Interventions in NCT04855747: REL-1017, Placebo.

What condition does NCT04855747 study?

NCT04855747 studies Major Depressive Disorder, Depression.

Is NCT04855747 still recruiting?

NCT04855747 is currently terminated. Last updated 6 November 2025.

Last reviewed 2025-11-06 · How we verify

NCT04855747: RELIANCE-II

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

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

Terminated Phase 3 Last updated 6 November 2025

What this trial tests

Phase 3 trial testing REL-1017 in Major Depressive Disorder in 236 participants. Terminated before completion.

Timeline

30 March 2021

Primary endpoint
31 December 2024

14 January 2025

Quick facts

Lead sponsor	Levomecor Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	236
Start date	30 March 2021
Primary completion	31 December 2024
Estimated completion	14 January 2025
Sites	70 locations across United States

Drugs / interventions tested

REL-1017 — full drug profile →
Placebo

Conditions studied

Major Depressive Disorder — all drugs for Major Depressive Disorder →
Depression — all drugs for Depression →

Sponsor

Levomecor Inc.

Who can join

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

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):

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
Ketamine in neuropsychiatric disorders: an update.
Johnston JN, Kadriu B, Kraus C, Henter ID, et al · · 2024 · cited 54× · PMID 37340091 · DOI 10.1038/s41386-023-01632-1
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
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
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
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
The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.
Shram MJ, Henningfield JE, Apseloff G, Gorodetzky CW, et al · · 2023 · cited 12× · PMID 37286536 · DOI 10.1038/s41398-023-02473-8
Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.
Vasiliu O. · · 2022 · cited 9× · PMID 35847011 · DOI 10.3389/fphar.2022.884155

Verify or expand the search:

Other trials of REL-1017

Trials testing the same drug.

NCT06011577 — Randomized, Double-Blind, Placebo-Controlled Trial of REL-1017 as Adjunctive Treatment for MDD · Phase 3 · terminated
NCT05081167 — A Study to Assess the Efficacy and Safety of REL-1017 as Monotherapy for Major Depressive Disorder (MDD) · Phase 3 · completed
NCT04855760 — Safety of REL-1017 for Major Depressive Disorder · Phase 3 · completed
NCT04688164 — A Study to Assess the Efficacy and Safety of REL-1017 as Adjunctive Treatment for Major Depressive Disorder (MDD) · Phase 3 · completed
NCT03051256 — Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With 25 mg or 50 mg Daily of REL-1017 in MDD · Phase 2 · completed

Other recruiting trials for Major Depressive Disorder

Currently open trials in the same condition.

NCT07219394 — Peer-Delivered Behavioral Activation in a CCBHC · NA · recruiting
NCT06705478 — Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disor · Phase 2 · recruiting
NCT06749392 — An Individual-specific Synchrony Signature · NA · recruiting
NCT07316803 — Group Intervention for Romantic Relationships in Young Adults With Severe Mental Illness · NA · recruiting
NCT07242105 — Optimizing Brain Excitability in Depression · NA · recruiting

Other Levomecor Inc. trials

Trials by the same sponsor.

NCT06011577 — Randomized, Double-Blind, Placebo-Controlled Trial of REL-1017 as Adjunctive Treatment for MDD · Phase 3 · terminated

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT04855747 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 9 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Levomecor Inc.
Last refreshed: 6 November 2025

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04855747.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing