Major Depressive Disorder (MDD)Phase 3NCT06735079
A Study to Evaluate the Efficacy and Safety of REL-1017 As Adjunctive Treatment of Major Depressive Disorder (MDD)
A Phase 3 study testing REL1017 (esmethadone HCI) (active drug) in people with Major Depressive Disorder (MDD), run by MGGM LLC at 2 sites in 2 countries.
Trial summary
Study Overview This clinical trial is a Phase 3 research study designed to test the safety and effectiveness of an investigational drug called REL-1017 (esmethadone HCl). The goal is to determine if REL-1017 can help people with major depressive disorder (MDD) who are already taking other antidepressant medications… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- REL1017 (esmethadone HCI) (active drug)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 27 Dec 2024to 1 Mar 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Written informed consent.
- Male or female participant, aged 18 to 65 years, inclusive, at Screening.
- Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive, at Screening.
- Participant understands the study requirements, is willing and able to commit to meet all study requirements, adhere to both approved ADT and study drug regimen, and complete all assessments and all scheduled visits, per Investigator judgment.
Who cannot join
- History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the Investigator would jeopardize the safety of the participant or the validity of the study results, including established QT prolongation, long QT syndrome, torsades de pointes, bradyarrhythmia, ventricular tachycardia, uncompensated heart failure (greater than NYHA Class 1 CHF), uncontrolled hypokalemia, or uncontrolled hypomagnesemia.
- Any medical, psychiatric condition, or social context that, in the opinion of the Investigator, is likely to unfavourably alter the risk-benefit of participant, to interfere with protocol compliance, or to confound safety or efficacy assessments.
- Triplicate 12-lead ECG with average QTcF ≥450 msec, and/or a QRS interval ≥120 msec at Screening.
- Poorly controlled diabetes as defined by a glycosylated hemoglobin (HbA1c) >8.5% (69 mmol/mol), despite standard care. (Note: re-screening of patients who has failed the screening process due to not meeting this exclusion criterion is allowed after diabetes treatment adjustment and level of glycosylated hemoglobin (HbA1c) back to <8.5%)
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Switzerland1 site
Clinical Trial Unit - Ente Ospedaliero Cantonale (CTU-EOC) Area Formazione medica e Ricerca (AFRi)
Lugano, Switzerland, 6900
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 for Major Depressive Disorder (MDD)
Study Overview This clinical trial is a Phase 3 research study designed to test the safety and effectiveness of an investigational drug called REL-1017 (esmethadone HCl). The goal is to determine if REL-1017 can help people with major depressive disorder (MDD) who are already taking other antidepressant medications but have not experienced enough improvement.
Why This Study Is Important MDD is a serious condition that affects mood, cognition, motivation, energy, and daily life. Some people do not respond fully to standard antidepressants. REL-1017 is being tested as an additional treatment to see if it can improve symptoms more effectively.
Read more
Who Can Participate The study is enrolling adults diagnosed with major depressive disorder who do not have enough relief from their current antidepressant medications. Specific criteria must be met to join the study.
What Happens in the Study Participants will be randomly assigned to receive either REL-1017 or a placebo (an inactive substance) along with their current antidepressant. This process helps researchers understand the effects of the drug. Neither the participants nor the researchers will know who receives REL-1017 or the placebo during the study.
Study Details Duration: The study involves several weeks of treatment and follow-up visits. Assessments: Participants will complete health evaluations, including physical exams and questionnaires, to monitor progress and side effects.
Costs: Study-related treatments and assessments are provided at no cost to participants.
Potential Benefits and Risks Benefits: Participants may experience improvements in depressive symptoms. Risks: As with any investigational medication, there may be side effects. All participants will be closely monitored by the study team.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- REL1017 (esmethadone HCI) (active drug), Placebo
- Keywords
- MDD, Esmethadone, Adjunctive therapy, REL-1017, NMDA
- 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.
REL1017 (esmethadone HCI) (active drug)Drug
REL-1017 is an investigational drug administered as an oral tablet, once daily. The dosing regimen includes a 75 mg dose on Day 1 (three tablets) in the clinic, followed by 25 mg daily (one tablet) at home from Day 2 to Day 28, with regular safety, efficacy, and tolerability assessments REL-1017 (esmethadone HCl) is under investigation as a novel NMDAR antagonist. Unlike racemic methadone, it lacks opioid-like effects such as dependency or respiratory depression. REL-1017 also lacks dissociative effects seen with more potent NMDAR antagonists such as ketamine. Finally, REL-1017 does not appear to have metabolic or neurological side effects.
PlaceboDrug
The placebo serves as a control to evaluate the effectiveness and safety of REL-1017. It is an inactive substance that matches the active drug in appearance but contains no active ingredients. The placebo group allows researchers to compare outcomes, such as changes in depressive symptoms, with the active drug group.
The double-blind design ensures neither participants nor researchers know who is receiving the active treatment or placebo, eliminating bias. The placebo also helps assess whether observed side effects are due to the drug or unrelated factors.
Participants are randomly assigned to receive either REL-1017 or the placebo, both administered once daily for 28 days. This helps establish REL-1017's clinical effectiveness and safety in treating Major Depressive Disorder (MDD).
| Study group | Role | What they receive |
|---|---|---|
| REL 1017-305 | Experimental | Not described Receives: Drug: REL1017 (esmethadone HCI) (active drug) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MADRS10
To evaluate the therapeutic efficacy of REL-1017 compared to placebo in participants with inadequate response to ongoing ADT at Day 28 on the Montgomery-Åsberg Depression Rating Scale (MADRS10) total score.
Scale: Montgomery-Åsberg Depression Rating Scale (MADRS)
Minimum and Maximum Values: The scale ranges from 0 to 60. Interpretation of Higher Scores: Higher scores indicate greater severity of depression.
Specific Ranges:
0-6: Normal/no symptoms. 7-19: Mild depression. 20-34: Moderate depression. 35-60: Severe depression.
Measured: 28 days
Secondary outcomes (4)
MADRS10
Decrease from Baseline to Day 7 of the MADRS10 total score
Scale: Montgomery-Åsberg Depression Rating Scale (MADRS)
Measured: 7 days
MADRS10
MADRS10 response rate (improvement ≥50% compared with total Baseline score) at Day 28
Scale: Montgomery-Åsberg Depression Rating Scale (MADRS)
Measured: 28 days
MADRS10
MADRS10 remission rate (total score ≤10) at Day 28
Scale: Montgomery-Åsberg Depression Rating Scale (MADRS)
Measured: 28 days
CGI-S
Decrease from Baseline to Day 28 of the CGI-S score
Scale: CGI-S
The CGI-S measures the severity of the disease using a 7-point Likert scale ranging from 1=normal, not at all ill to 7=among the most extremely ill participants
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2024
- Study start27 Dec 2024 (estimated)
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Mar 2027 (estimated)
Why it stopped: The study was withdrawn based on business-related matters and there are no new safety concerns related to the trial. No patients were enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- MGGM LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06735079
- Sponsor's protocol ID
- REL-1017-305
- Status last verified
- Feb 2025
- First submitted
- 13 Dec 2024
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. 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 for Major Depressive Disorder (MDD)
- ClinicalTrials.gov ID
- NCT06735079
- Acronym / sponsor ID
- REL-1017-305
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- MDD, Esmethadone, Adjunctive therapy, REL-1017, NMDA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was withdrawn based on business-related matters and there are no new safety concerns related to the trial. No patients were enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- MGGM LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Dec 2024 (estimated)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 16 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Overview This clinical trial is a Phase 3 research study designed to test the safety and effectiveness of an investigational drug called REL-1017 (esmethadone HCl). The goal is to determine if REL-1017 can help people with major depressive disorder (MDD) who are already taking other antidepressant medications but have not experienced enough improvement.
Why This Study Is Important MDD is a serious condition that affects mood, cognition, motivation, energy, and daily life. Some people do not respond fully to standard antidepressants. REL-1017 is being tested as an additional treatment to see if it can improve symptoms more effectively.
Who Can Participate The study is enrolling adults diagnosed with major depressive disorder who do not have enough relief from their current antidepressant medications. Specific criteria must be met to join the study.
What Happens in the Study Participants will be randomly assigned to receive either REL-1017 or a placebo (an inactive substance) along with their current antidepressant. This process helps researchers understand the effects of the drug. Neither the participants nor the researchers will know who receives REL-1017 or the placebo during the study.
Study Details Duration: The study involves several weeks of treatment and follow-up visits. Assessments: Participants will complete health evaluations, including physical exams and questionnaires, to monitor progress and side effects.
Costs: Study-related treatments and assessments are provided at no cost to participants.
Potential Benefits and Risks Benefits: Participants may experience improvements in depressive symptoms. Risks: As with any investigational medication, there may be side effects. All participants will be closely monitored by the study team.
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 1017-305 | Experimental | Drug: REL1017 (esmethadone HCI) (active drug) |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent.
- Male or female participant, aged 18 to 65 years, inclusive, at Screening.
- Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive, at Screening.
- Participant understands the study requirements, is willing and able to commit to meet all study requirements, adhere to both approved ADT and study drug regimen, and complete all assessments and all scheduled visits, per Investigator judgment.
Key exclusion criteria (4 listed)
- History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the Investigator would jeopardize the safety of the participant or the validity of the study results, including established QT prolongation, long QT syndrome, torsades de pointes, bradyarrhythmia, ventricular tachycardia, uncompensated heart failure (greater than NYHA Class 1 CHF), uncontrolled hypokalemia, or uncontrolled hypomagnesemia.
- Any medical, psychiatric condition, or social context that, in the opinion of the Investigator, is likely to unfavourably alter the risk-benefit of participant, to interfere with protocol compliance, or to confound safety or efficacy assessments.
- Triplicate 12-lead ECG with average QTcF ≥450 msec, and/or a QRS interval ≥120 msec at Screening.
- Poorly controlled diabetes as defined by a glycosylated hemoglobin (HbA1c) >8.5% (69 mmol/mol), despite standard care. (Note: re-screening of patients who has failed the screening process due to not meeting this exclusion criterion is allowed after diabetes treatment adjustment and level of glycosylated hemoglobin (HbA1c) back to <8.5%)
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 |
|---|---|---|
| REL1017 (esmethadone HCI) (active drug)REL-1017 is an investigational drug administered as an oral tablet, once daily. The dosing regimen includes a 75 mg dose on Day 1 (three tablets) in the clinic, followed by 25 mg daily (one tablet) at home from Day 2 to Day 28, with regular safety, efficacy, and tolerability assessments REL-1017 (esmethadone HCl) is under investigation as a novel NMDAR antagonist. Unlike racemic methadone, it lacks opioid-like effects such as dependency or respiratory depression. REL-1017 also lacks dissociative effects seen with more potent NMDAR antagonists such as ketamine. Finally, REL-1017 does not appear to have metabolic or neurological side effects. | Drug | REL 1017-305 |
| PlaceboThe placebo serves as a control to evaluate the effectiveness and safety of REL-1017. It is an inactive substance that matches the active drug in appearance but contains no active ingredients. The placebo group allows researchers to compare outcomes, such as changes in depressive symptoms, with the active drug group. The double-blind design ensures neither participants nor researchers know who is receiving the active treatment or placebo, eliminating bias. The placebo also helps assess whether observed side effects are due to the drug or unrelated factors. Participants are randomly assigned to receive either REL-1017 or the placebo, both administered once daily for 28 days. This helps establish REL-1017's clinical effectiveness and safety in treating Major Depressive Disorder (MDD). | Drug | Placebo |
Primary outcome
MADRS10
Time frame: 28 days
To evaluate the therapeutic efficacy of REL-1017 compared to placebo in participants with inadequate response to ongoing ADT at Day 28 on the Montgomery-Åsberg Depression Rating Scale (MADRS10) total score. Scale: Montgomery-Åsberg Depression Rating Scale (MADRS) Minimum and Maximum Values: The scale ranges from 0 to 60. Interpretation of Higher Scores: Higher scores indicate greater severity of depression. Specific Ranges: 0-6: Normal/no symptoms. 7-19: Mild depression. 20-34: Moderate depression. 35-60: Severe depression.
4 secondary outcomes
MADRS10
Time frame: 7 days
MADRS10
Time frame: 28 days
MADRS10
Time frame: 28 days
CGI-S
Time frame: 28 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing REL1017 (esmethadone HCI) (active drug) in people with Major Depressive Disorder (MDD), run by MGGM LLC at 2 sites in 2 countries.
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 4 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: withdrawn, as of the sponsor's last update on 7 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 2 sites in Italy, Switzerland. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
MADRS10 (time frame: 28 days). 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 7 Feb 2025.