Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With 25 mg or 50 mg Daily of REL-1017 in MDD

Summary

This a Phase 2a, multicenter, randomized, double-blind, placebo controlled 3 arm study to assess the safety and tolerability of multiple oral doses of REL-1017 25 mg and 50 mg as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder (MDD). The patients will be adults with MDD who are diagnosed with a current MDE who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication. This population will provide the opportunity to compare the safety and efficacy effects of treatment with an approved antidepressant in conjunction with REL-1017 versus the effects of an antidepressant alone. This study includes in-patient and out-patient periods.

Timeline

Start

2018-05-11

Primary completion

2019-07-30

Completion

2019-09-30

Outcome

Met primary endpoint

release “The results of this Phase 2 study demonstrate a solid and rapid antidepressant effect and overall favorable tolerability and safety profile of REL-1017” relmada.com ↗

release “Findings show that REL-1017 has rapid onset and sustained antidepressant efficacy with statistically significant differences compared to placebo on all efficacy measures” relmada.com ↗

release “In a Phase 2 trial, REL-1017 demonstrated rapid, robust, and sustained antidepressant effects with statistically significant improvements compared to placebo.” relmada.com ↗

Publications

• Results Fava M, Stahl S, Pani L, De Martin S, Pappagallo M, Guidetti C, Alimonti A, Bettini E, Mangano RM, Wessel T, de Somer M, Caron J, Vitolo OV, DiGuglielmo GR, Gilbert A, Mehta H, Kearney M, Mattarei A, Gentilucci M, Folli F, Traversa S, Inturrisi CE, Manfredi PL. REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial. Am J Psychiatry. 2022 Feb;179(2):122-131. doi: 10.1176/appi.ajp.2021.21020197. Epub 2021 Dec 22.
• Results Guidetti C, Serra G, Pani L, Pappagallo M, Maglio G, Martin S, Mattarei A, Folli F, Manfredi PL, Fava M. Subanalysis of Subjective Cognitive Measures From a Phase 2, Double-Blind, Randomized Trial of REL-1017 in Patients With Major Depressive Disorder. Prim Care Companion CNS Disord. 2023 Feb 14;25(1):22m03267. doi: 10.4088/PCC.22m03267.
• Guidetti C, De Martin S, Serra G, Apicella M, Pani L, Pappagallo M, Mattarei A, Folli F, Manfredi P, Fava M. Effect of Time From Onset of Major Depressive Disorder on the Therapeutic Response to Esmethadone (REL-1017). J Clin Psychiatry. 2024 May 13;85(2):22m14735. doi: 10.4088/JCP.22m14735.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Esmethadone	Small molecule	25 mg	Oral
Subject	Esmethadone	Small molecule	50 mg	Oral

Indications