Scientific Poster Session II - Original Research

Original Research
  Sunday, November 12, 2023
  12:45 PM–02:15 PM

Abstract

Introduction: Esmethadone (REL-1017) is an N-methyl-D-aspartate receptor uncompetitive antagonist and antidepressant candidate with promising safety, tolerability, and efficacy results from Phase 1 and 2 trials. Available data indicate that REL-1017 has no meaningful opioid agonist action or abuse potential.

Research Question or Hypothesis: We hypothesized that there would be no indication of abuse potential and dependence in patients with major depressive disorder (MDD).

Study Design: Studies 301 and 303 were 28-day, outpatient, Phase 3, randomized, double-blind, placebo-controlled trials of once-daily oral 25 mg REL-1017 (Day 1 loading dose 75 mg) in patients with MDD.

Methods: In Study 301, placebo or REL-1017 was administered as adjunctive treatment to 227 patients unresponsive to standard antidepressants; in Study 303, placebo or REL-1017 was administered to 232 patients as monotherapy. We performed a safety analysis of all adverse events (AEs) and collected narratives for AEs potentially related to abuse. We assessed “drug liking,” “drug high,” and “desire to take the drug again” with a 0- to 100-point visual analogue scale (VAS). We used the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS^®) to assess potentially abuse-related events. We assessed withdrawal after abrupt treatment discontinuation with the Physician Withdrawal Checklist (PWC), Clinical Opiate Withdrawal Scale (COWS), and Subjective Opiate Withdrawal Scale (SOWS).

Results: Among the 459 patients receiving any study drug, AEs were predominantly mild or moderate and transient. AEs potentially related to abuse were not correlated to other measures of abuse potential and did not differ among groups. There were no differences in VAS scores and no indication of abuse on the MADDERS^®. Among 354 patients who participated in the safety withdrawal assessment, change from baseline on the PWC, COWS, and SOWS did not differ between groups.

Conclusion: In 2 contemporary, Phase 3, controlled MDD studies of REL-1017, there were no indications of meaningful abuse potential or dependence.

Presenting Author

Marco Pappagallo MD
Relmada Therapeutics

Authors

David Bushnell MS
Thomas Kosten MD
Paolo Manfredi MD
Charles Gorodetzky MD, PhD
Clotilde Guidetti MD
Jack Henningfield PhD
Charles Inturrisi PhD
Cedric O'Gorman MD, MBA
Sara De Martin PhD
Franco Folli MD, PhD
Sergio Traversa PharmD, MBA
Frank Vocci PhD
Frank Sapienza MS
Megan Shram PhD