Safety of REL-1017 for Major Depressive Disorder (RELIANCE-OLS)

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: REL-1017

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.

• Study Type: Interventional
• Enrollment (Actual): 627
• Phase: Phase 3

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: REL-1017; 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.

Drug: REL-1017; REL-1017 tablet; Other Names: Esmethadone HCl

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	12 Month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the MADRS10 Total Score From Baseline to Month 3	Therapeutic efficacy of REL-1017 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.	3 Month
Change in the MADRS10 Total Score From Baseline to Month 12	Therapeutic efficacy of REL-1017 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.	12 Month

Collaborators and Investigators

• Sponsor: Relmada Therapeutics, Inc.
• Investigators: Study Director: Marco Pappagallo, MD, Relmada Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): July 27, 2023
• Study Completion (Actual): July 27, 2023

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: REL-1017
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: REL-1017-310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No