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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| REL-1017 | Experimental | A 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 25 mg REL-1017 in addition to their ongoing antidepressant. |
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| Placebo | Placebo Comparator | Three tablets of matching placebo will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 1 placebo tablet in addition to their ongoing antidepressant. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| REL-1017 | Drug | REL-1017 tablet |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in the MADRS10 Total Score From Baseline to 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. | Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| MADRS10 Remission Rate (Total Score ≤10) at 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. | Day 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marco Pappagallo, MD | Relmada Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Relmada Site | Miami | Florida | 33175 | United States | ||
| Relmada Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38917366 | Result | Fava M, Stahl SM, Pani L, De Martin S, Cutler AJ, Maletic V, Gorodetzky CW, Vocci FJ, Sapienza FL, Kosten TR, Kroger C, Champasa P, O'Gorman C, Guidetti C, Alimonti A, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M. Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial. J Clin Psychiatry. 2024 Jun 17;85(3):24m15265. doi: 10.4088/JCP.24m15265. | |
| 41749468 |
| Label | URL |
|---|---|
| Study Homepage | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | REL-1017 | A 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 25 mg REL-1017 in addition to their ongoing antidepressant (ADT). REL-1017: REL-1017 tablet |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 1, 2022 |
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| Placebo |
| Drug |
Placebo tablet |
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| MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at 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. | Day 28 |
| Miami Springs |
| Florida |
| 33166 |
| United States |
| Relmada Site | Palm Bay | Florida | 32905 | United States |
| Relmada Site | Decatur | Georgia | 30030 | United States |
| Relmada Site | Chicago | Illinois | 60634 | United States |
| Relmada Site | Boston | Massachusetts | 02116 | United States |
| Relmada Site | Watertown | Massachusetts | 02472 | United States |
| Relmada Site | O'Fallon | Missouri | 63368 | United States |
| Relmada Site | New York | New York | 10128 | United States |
| Relmada Site | Cincinnati | Ohio | 45215 | United States |
| Relmada Site | Austin | Texas | 78737 | United States |
| Derived |
| Guidetti C, Papakostas GI, Stahl S, Pani L, De Martin S, Mattarei A, Comai S, Kroger C, Champasa P, Gorodetzky CW, Vocci FJ, Kosten TR, Bushnell D, Kappler M, Folli F, Inturrisi CE, Pappagallo M, Manfredi PL, Fava M. Depression severity and efficacy outcomes: post hoc analyses from a phase 3 trial of esmethadone for the adjunctive treatment of major depressive disorder with inadequate response to standard antidepressants. Int Clin Psychopharmacol. 2026 Jul 1;41(4):213-224. doi: 10.1097/YIC.0000000000000618. Epub 2026 Feb 17. |
Three tablets of matching placebo will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 1 placebo tablet in addition to their ongoing antidepressant (ADT). Placebo: Placebo tablet |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | REL-1017 | A 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 25 mg REL-1017 in addition to their ongoing antidepressant. REL-1017: REL-1017 tablet |
| BG001 | Placebo | Three tablets of matching placebo will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 1 placebo tablet in addition to their ongoing antidepressant. Placebo: Placebo tablet |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in the MADRS10 Total Score From Baseline to 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. | Full Analysis Set: defined as all subjects who received at least one dose of study medication and were assessed for the primary efficacy endpoint at both Baseline and Day 28 | Posted | Mean | Standard Deviation | score on a scale | Day 28 |
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| Secondary | MADRS10 Remission Rate (Total Score ≤10) at 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. | Full Analysis Set: defined as all subjects who received at least one dose of study medication and had the Baseline assessment of the primary efficacy endpoint performed | Posted | Number | 95% Confidence Interval | percentage of participants in remission | Day 28 |
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| Secondary | MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at 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. | Full Analysis Set: defined as all subjects who received at least one dose of study medication and had the Baseline assessment of the primary efficacy endpoint performed | Posted | Number | 95% Confidence Interval | percentage of responders | Day 28 |
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TEAE that starts or worsens at any time after initiation of study drug collected up to 14 days post treatment (Day 42).
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 14 days post treatment (Day 42) as collected in the Safety Analysis Set.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | REL-1017 25 mg | A 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 25 mg REL-1017 in addition to their ongoing antidepressant. REL-1017: REL-1017 tablet | 0 | 113 | 3 | 113 | 34 | 113 |
| EG001 | Placebo | Three tablets of matching placebo will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 1 placebo tablet in addition to their ongoing antidepressant. Placebo: Placebo tablet | 0 | 114 | 0 | 114 | 34 | 114 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal Ideation | Psychiatric disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Cholecystitis | Hepatobiliary disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marco Pappagallo, MD | Relmada Therapeutics | 786-638-7384 | info@relmada.com |
| Feb 16, 2024 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Participants |
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