Major Depressive DisorderPhase 3RELIANCE-IINCT04855747
A Study to Assess the Efficacy and Safety of REL-1017 as Adjunctive Treatment for Major Depressive Disorder (MDD)
A Phase 3 study testing REL-1017 in people with Major Depressive Disorder and Depression, run by Levomecor Inc. at 70 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Depression
- What is being tested?
- REL-1017
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 236 participants
- Where
- 70 sitesUnited States
- Study dates
- 30 Mar 2021to 14 Jan 2025
- 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
- Body mass index (BMI) between 18.0 and 35.0 kg/m2.
- Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD.
- Current Major Depressive Episode (MDE).
- Treated on approved, stable first-line anti-depressant therapy with inadequate response to 1 to 3 valid courses of treatment with a depressant medication in the current MDE.
Who cannot join
- 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.
- Poorly controlled diabetes as defined by HbA1c > 7.5%, despite standard care. Subjects with HbA1c >7.5% may continue in the study if approved by the Relmada Medical Monitor.
- Having received ketamine or esketamine within 60 days prior to Screening.
Trial locations and contacts
70 sites in 1 country.
70 sites in 1 country
United States70 sites
Relmada Site
Anaheim, California, 92805
Relmada Site
Austin, Texas, 78737
Relmada Site
Austin, Texas, 78759
Relmada Site
Baltimore, Maryland, 21208
Relmada Site
Beachwood, Ohio, 44122
Relmada Site
Beaumont, Texas, 77702
Relmada Site
Bel Air, Maryland, 21015
Relmada Site
Bellaire, Texas, 77401
Relmada Site
Bellflower, California, 90706
Relmada Site
Bloomfield Hills, Michigan, 48302
Relmada Site
Boise, Idaho, 83704
Relmada Site
Boston, Massachusetts, 02131
Relmada Site
Brandon, Florida, 33511
Relmada Site
Bryant, Arkansas, 72022
Relmada Site
Cedarhurst, New York, 11516
Relmada Site
Chandler, Arizona, 85226
Relmada Site
Chandler, Arizona, 85286
Relmada Site
Chicago, Illinois, 60611
Relmada Site
Chicago, Illinois, 60634
Relmada Site
Cincinnati, Ohio, 45215
Relmada Site
Cincinnati, Ohio, 45219
Relmada Site
Dallas, Texas, 75243
Relmada Site
Denver, Colorado, 80209
Relmada Site
Draper, Utah, 84020
Relmada Site
Elgin, Illinois, 60123
Relmada Site
Encino, California, 91316
Relmada Site
Everett, Washington, 98201
Relmada Site
Friendswood, Texas, 77546
Relmada Site
Gaithersburg, Maryland, 20877
Relmada Site
Hialeah, Florida, 33015
Relmada Site
Homewood, Alabama, 35209
Relmada Site
Houston, Texas, 77081
Relmada Site
Jacksonville, Florida, 32256
Relmada Site
Lafayette, California, 94549
Relmada Site
Las Vegas, Nevada, 89121
Relmada Site
Los Angeles, California, 90015
Relmada Site
Maitland, Florida, 32751
Relmada Site
Mankato, Minnesota, 56001
Relmada Site
Marrero, Louisiana, 70072
Relmada Site
Memphis, Tennessee, 38119
Relmada Site
Miami, Florida, 33122
Relmada Site
Miami, Florida, 33125
Relmada Site
Miami, Florida, 33133
Relmada Site
Miami, Florida, 33136
Relmada Site
Miami, Florida, 33174
Relmada Site
Miami Springs, Florida, 33166
Relmada Site
Monroe, North Carolina, 28112
Relmada Site
Newport Beach, California, 92660
Relmada Site
Okeechobee, Florida, 34972
Relmada Site
Orange, California, 92868
Relmada Site
Overland Park, Kansas, 66210
Relmada Site
Philadelphia, Pennsylvania, 19104
Relmada Site
Phoenix, Arizona, 85016
Relmada Site
Portsmouth, Virginia, 23703
Relmada Site
Redlands, California, 92374
Relmada Site
Rutland, Vermont, 05701
Relmada Site
Santa Ana, California, 92705
Relmada Site
Savannah, Georgia, 31406
Relmada Site
Sherman, Texas, 75092
Relmada Site
Stanford, California, 94305
Relmada Site
State College, Pennsylvania, 16801
Relmada Site
Tampa, Florida, 33607
Relmada Site
Temecula, California, 92591
Relmada Site
Toms River, New Jersey, 08755
Relmada Site
Tucson, Arizona, 85704
Relmada Site
Upland, California, 91786
Relmada Site
Weldon Spring, Missouri, 63304
Relmada Site
West Palm Beach, Florida, 33407
Relmada Site
Westlake, Ohio, 44145
Relmada Site
Wichita Falls, Texas, 76309
About this study
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study to Assess the Efficacy and Safety of REL-1017 as Adjunctive Treatment of Major Depressive Disorder (The RELIANCE-II Study)
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.
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- REL-1017, Placebo
- Keywords
- REL-1017, Relmada, NMDA Receptor Antagonist, Esmethadone, Adjunctive, Antidepressant, Reliance, Depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REL-1017Drug
Also called Esmethadone
REL-1017 tablet
PlaceboDrug
Placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| REL-1017 25 mg | Experimental | During the double blind treatment period (28 days), participants will take 1 tablet of REL-1017 25 mg, orally, per day in addition to their ongoing antidepressant (ADT) Receives: Drug: REL-1017 |
| Placebo | Placebo comparator | During the double blind treatment period (28 days), participants will take 1 tablet of placebo, orally, per day in addition to their ongoing antidepressant (ADT). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Day 28 in MADRS Total Score
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. The total score is calculated as the sum of 10 items, each scored from 0 to 6, resulting in a total score range of 0 to 60. Lower scores indicate less severe depressive symptoms and a better outcome, whereas higher scores indicate more severe depressive symptoms and a worse outcome. The outcome measure reports the change in MADRS total score from Baseline to Day 28. Change was calculated as Day 28 score minus Baseline score.
Measured: Baseline and Day 28
Secondary outcomes (4)
Change From Baseline to Day 7 in MADRS Total Score
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. The total score is calculated as the sum of 10 items, each scored from 0 to 6, resulting in a total score range of 0 to 60. Lower scores indicate less severe depressive symptoms and a better outcome, whereas higher scores indicate more severe depressive symptoms and a worse outcome. The outcome measure reports the change in MADRS total score from Baseline to Day 7. Change was calculated as Day 7 score minus Baseline score.
Measured: Day 7
Change From Baseline to Day 28 in Clinical Global Impression-Severity (CGI-S) Score
Clinical Global Impression-Severity (CGI-S) is a clinician-rated assessment of illness severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Lower scores indicate less severe illness and a better outcome, whereas higher scores indicate more severe illness and a worse outcome. The outcome measure reports the change in CGI-S score from Baseline to Day 28. Change was calculated as Day 28 score minus Baseline score
Measured: Day 28
MADRS10 Remission Rate at Day 28
Remission was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score ≤10 at Day 28. The MADRS total score ranges from 0 to 60, with lower scores indicating less severe depressive symptoms and a better outcome.
Measured: Day 28
MADRS10 Response Rate at Day 28
Response was defined as a ≥50% reduction from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS total score ranges from 0 to 60, with lower scores indicating less severe depressive symptoms and a better outcome.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start30 Mar 2021
- Primary completion31 Dec 2024
- Study completion14 Jan 2025
Why it stopped: Study REL-1017-302 was terminated early by the Sponsor following the prespecified interim analysis for sample size re-estimation at approximately 75% enrollment of the planned sample size (N=280). Safety data were collected.
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.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 236 participants (actual)
Sponsor and investigators
- Lead sponsor
- Levomecor Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Greene, PhD, Study director, Relmada Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04855747
- Sponsor's protocol ID
- REL-1017-302
- Acronym
- RELIANCE-II
- Status last verified
- Jun 2026
- First submitted
- 19 Apr 2021
- Last updated
- 10 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study to Assess the Efficacy and Safety of REL-1017 as Adjunctive Treatment of Major Depressive Disorder (The RELIANCE-II Study)
- ClinicalTrials.gov ID
- NCT04855747
- Acronym / sponsor ID
- RELIANCE-II / REL-1017-302
- Conditions
- Major Depressive Disorder, Depression
- Keywords
- REL-1017, Relmada, NMDA Receptor Antagonist, Esmethadone, Adjunctive, Antidepressant, Reliance, Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study REL-1017-302 was terminated early by the Sponsor following the prespecified interim analysis for sample size re-estimation at approximately 75% enrollment of the planned sample size (N=280). Safety data were collected.
- Enrolment
- 236 participants (actual)
- Lead sponsor
- Levomecor Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Mar 2021 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 14 Jan 2025 (actual)
- First posted
- 22 Apr 2021 (actual)
- Results
- Posted 10 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| REL-1017 25 mg | Experimental | Drug: REL-1017During the double blind treatment period (28 days), participants will take 1 tablet of REL-1017 25 mg, orally, per day in addition to their ongoing antidepressant (ADT) |
| Placebo | Placebo comparator | Drug: PlaceboDuring the double blind treatment period (28 days), participants will take 1 tablet of placebo, orally, per day in addition to their ongoing antidepressant (ADT). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Body mass index (BMI) between 18.0 and 35.0 kg/m2.
- Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD.
- Current Major Depressive Episode (MDE).
- Treated on approved, stable first-line anti-depressant therapy with inadequate response to 1 to 3 valid courses of treatment with a depressant medication in the current MDE.
Key exclusion criteria (5 listed)
- 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.
- Poorly controlled diabetes as defined by HbA1c > 7.5%, despite standard care. Subjects with HbA1c >7.5% may continue in the study if approved by the Relmada Medical Monitor.
- Having received ketamine or esketamine within 60 days prior to Screening.
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: EsmethadoneREL-1017 tablet | Drug | REL-1017 25 mg |
| PlaceboPlacebo tablet | Drug | Placebo |
Primary outcome
Change From Baseline to Day 28 in MADRS Total Score
Time frame: Baseline and Day 28
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. The total score is calculated as the sum of 10 items, each scored from 0 to 6, resulting in a total score range of 0 to 60. Lower scores indicate less severe depressive symptoms and a better outcome, whereas higher scores indicate more severe depressive symptoms and a worse outcome. The outcome measure reports the change in MADRS total score from Baseline to Day 28. Change was calculated as Day 28 score minus Baseline score.
4 secondary outcomes
Change From Baseline to Day 7 in MADRS Total Score
Time frame: Day 7
Change From Baseline to Day 28 in Clinical Global Impression-Severity (CGI-S) Score
Time frame: Day 28
MADRS10 Remission Rate at Day 28
Time frame: Day 28
MADRS10 Response Rate at Day 28
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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.
Paul Greene, PhD study director
Relmada Therapeutics
70 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 and Depression, run by Levomecor Inc. at 70 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 4 inclusion and 5 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: stopped early, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 70 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. Some participants in this study may receive a placebo. 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 10 Jul 2026). 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?
Change From Baseline to Day 28 in MADRS Total Score (time frame: Baseline and Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jul 2026.