Major Depressive DisorderPhase 3RELIANCE-OLSNCT04855760

Safety of REL-1017 for Major Depressive Disorder

A Phase 3 study testing REL-1017 in people with Major Depressive Disorder, run by Relmada Therapeutics, Inc. at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: REL-1017
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 627 participants
Where: 9 sitesUnited States
Study dates: 1 Apr 2021to 27 Jul 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults 18 to 65 years, inclusive.
Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD.
Current major depressive episode.

Who cannot join

Any current and primary psychiatric disorder other than Major Depressive 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.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

Relmada Site
Boston, Massachusetts, 02116
Relmada Site
Chicago, Illinois, 60634
Relmada Site
Chicago, Illinois, 60640
Relmada Site
Miami, Florida, 33015
Relmada Site
Miami, Florida, 33175
Relmada Site
Orlando, Florida, 32801
Relmada Site
Palm Bay, Florida, 32905
Relmada Site
Staten Island, New York, 10312
Relmada Site
Watertown, Massachusetts, 02472

Other trials in United States

About this study

Official title: A Phase 3, Multicenter, Open-Label Study to Assess the Long-Term Safety of REL-1017 as a Treatment of Major Depressive Disorder

This was a 1-year, multicenter, open-label, long-term study to assess the safety of REL-1017 once daily (QD) as monotherapy or as adjunctive treatment of Major Depressive Disorder. Adjunctive study participants continued to take their current antidepressant therapy in addition to the study drug for the duration of the treatment period.

Read the detailed description

This was a multicenter, open-label, long-term study of REL-1017 to evaluate the long-term safety and long-term durability of response in patients with MDD. Patients who completed previous randomized, double-blind Phase 3 trials (NCT04688164, NCT04855747, NCT05081167) of REL-1017 as adjunctive therapy or monotherapy for MDD were asked to continue treatment with REL-1017 25 mg daily for up to 1 year. De novo patients who satisfied inclusion/exclusion criteria also were enrolled and received a 75 mg loading dose of REL-1017 on Day 1 followed by a maintenance dose of 25 mg REL-1017 daily for the remainder of the study (Days 2-365). When REL-1017 was administered as adjunctive treatment, patients continued to use a stable dosage of their concomitant antidepressants.

Conditions: Major Depressive Disorder
Being tested: REL-1017
Keywords: REL-1017
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

REL-1017Drug
Also called Esmethadone HCl
REL-1017 tablet

Study groups in NCT04855760
Study group	Role	What they receive
REL-1017	Experimental	Roll-over participants received 25 mg REL-1017 (one 25 mg REL-1017 tablet), orally, per day, either as a monotherapy or in addition to their ongoing antidepressant (ADT), rolling over from the monotherapy study REL-1017-303 or the adjunctive therapy studies REL-1017-301 and REL-1017-302, respectively. De Novo participants received a 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) on Day-1 of the 365-day treatment period. From Day-2 to Day-365, participants received 25 mg REL-1017 either as monotherapy or as adjunctive therapy. Receives: Drug: REL-1017

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)
Subjects with at least one Treatment Emergent Adverse Events (TEAEs)
Measured: 52 weeks

Secondary outcomes (11)

Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3
Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 3.
A negative change from baseline indicates shortening of the QTcF.
Measured: 3 Month
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6
Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 6.
A negative change from baseline indicates shortening of the QTcF.
Measured: 6 Month
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12
Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 12.
A negative change from baseline indicates shortening of the QTcF.
Measured: 12 Month
Change in Diastolic Blood Pressure From Baseline to Month 3
Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3.
A negative change from baseline indicates a reduction in Diastolic Blood Pressure.
Measured: 3 Month
Change in Diastolic Blood Pressure From Baseline to Month 12
Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12.
A negative change from baseline indicates a reduction in Diastolic Blood Pressure.
Measured: 12 Month
Change in Systolic Blood Pressure From Baseline to Month 3
Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3.
A negative change from baseline indicates a reduction in Systolic Blood Pressure.
Measured: 3 Month
Change in Systolic Blood Pressure From Baseline to Month 12
Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12.
A negative change from baseline indicates a reduction in Systolic Blood Pressure.
Measured: 12 Month
Change in Heart Rate From Baseline to Month 3
Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 3.
A negative change from baseline indicates a reduction in Heart Rate.
Measured: 3 Month
Change in Heart Rate From Baseline to Month 12
Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 12.
A negative change from baseline indicates a reduction in Heart Rate.
Measured: 12 Month
Change in Weight From Baseline to Month 3
Overall Safety of REL-1017 as measured by Weight From Baseline to Month 3.
A negative change from baseline indicates a reduction in Weight.
Measured: 3 Month
Change in Weight From Baseline to Month 12
Overall Safety of REL-1017 as measured by Weight From Baseline to Month 12.
A negative change from baseline indicates a reduction in Weight.
Measured: 12 Month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Apr 202127 Jul 2023

First posted22 Apr 2021
Study start1 Apr 2021
Primary completion27 Jul 2023
Study completion27 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 627 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04855760
Sponsor's protocol ID: REL-1017-310
Acronym: RELIANCE-OLS
Status last verified: Jan 2023
First submitted: 19 Apr 2021
Last updated: 11 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Expanded access: Available

Publications

Fava M, Pani L, De Martin S, Cutler AJ, Gorodetzky CW, Vocci FJ, Sapienza FL, Kosten TR, Kroger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M. Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study. J Clin Psychiatry. 2025 Feb 17;86(1):24m15438. doi: 10.4088/JCP.24m15438.
PubMed 39999772

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Multicenter, Open-Label Study to Assess the Long-Term Safety of REL-1017 as a Treatment of Major Depressive Disorder
ClinicalTrials.gov ID: NCT04855760
Acronym / sponsor ID: RELIANCE-OLS / REL-1017-310
Conditions: Major Depressive Disorder
Keywords: REL-1017
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 627 participants (actual)
Lead sponsor: Relmada Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 1 Apr 2021 (actual)
Primary completion: 27 Jul 2023 (actual)
Study completion: 27 Jul 2023 (actual)
First posted: 22 Apr 2021 (actual)
Results: Posted 9 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
REL-1017	Experimental	Drug: REL-1017Roll-over participants received 25 mg REL-1017 (one 25 mg REL-1017 tablet), orally, per day, either as a monotherapy or in addition to their ongoing antidepressant (ADT), rolling over from the monotherapy study REL-1017-303 or the adjunctive therapy studies REL-1017-301 and REL-1017-302, respectively. De Novo participants received a 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) on Day-1 of the 365-day treatment period. From Day-2 to Day-365, participants received 25 mg REL-1017 either as monotherapy or as adjunctive therapy.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Adults 18 to 65 years, inclusive.
Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD.
Current major depressive episode.

Key exclusion criteria (3 listed)

Any current and primary psychiatric disorder other than Major Depressive 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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
REL-1017Also: Esmethadone HClREL-1017 tablet	Drug	REL-1017

Primary outcome

Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: 52 weeks
Subjects with at least one Treatment Emergent Adverse Events (TEAEs)

11 secondary outcomes

Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3
Time frame: 3 Month
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6
Time frame: 6 Month
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12
Time frame: 12 Month
Change in Diastolic Blood Pressure From Baseline to Month 3
Time frame: 3 Month
Change in Diastolic Blood Pressure From Baseline to Month 12
Time frame: 12 Month
Change in Systolic Blood Pressure From Baseline to Month 3
Time frame: 3 Month
Change in Systolic Blood Pressure From Baseline to Month 12
Time frame: 12 Month
Change in Heart Rate From Baseline to Month 3
Time frame: 3 Month
Change in Heart Rate From Baseline to Month 12
Time frame: 12 Month
Change in Weight From Baseline to Month 3
Time frame: 3 Month
Change in Weight From Baseline to Month 12
Time frame: 12 Month

Results and safety

Results posted to the registry on 9 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
REL-1017	627	182

Primary outcome: Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)

Time frame: 52 weeks. Number. Unit: participants

Measure	REL-1017 n = 624
Value	350

Population analysed: Safety Analysis Set: All participants who received at least 1 dose of study drug.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: A Treatment Emergent Adverse Event (TEAE) is defined as an Adverse Event (AE) that starts or worsens at any time after initiation of study drug collected up to 1 month post treatment (Day 395) as collected in the Safety Analysis Set.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
REL-1017	8 of 624 (1.3%)	142 of 624 (22.8%)	0 of 624

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39999772Fava M, Pani L, De Martin S, Cutler AJ, Gorodetzky CW, Vocci FJ, Sapienza FL, Kosten TR, Kroger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M. Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study. J Clin Psychiatry. 2025 Feb 17;86(1):24m15438. doi: 10.4088/JCP.24m15438.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marco Pappagallo, MD study director

Relmada Therapeutics

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing REL-1017 in people with Major Depressive Disorder, run by Relmada Therapeutics, Inc. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs) (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04855760, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025; AzTrials last refreshed its copy on 7 Nov 2026.