Mixed Results for Solriamfetol in MDD Patients W/Wo Excessive Daytime Sleepiness

Topline results were announced from a phase 3 trial evaluating solriamfetol for the treatment of major depressive disorder (MDD) with and without severe excessive daytime sleepiness (EDS).

Solriamfetol is a dopamine and norepinephrine reuptake inhibitor, trace amine-associated receptor 1 agonist, and 5-HT_1A agonist. It is currently approved under the brand name Sunosi^® to improve wakefulness in adult patients with EDS associated with narcolepsy or obstructive sleep apnea.

The 6-week, randomized, double-blind, placebo-controlled PARADIGM trial (ClinicalTrials.gov Identifier: NCT06360419) investigated the safety and efficacy of solriamfetol in patients with a primary diagnosis of MDD without psychotic features. The Epworth Sleepiness Scale (ESS) was used to assess EDS. Of the 346 participants, 51 had severe EDS (ESS score ≥16).

Study participants were randomly assigned to receive solriamfetol 300mg or placebo orally once daily for 6 weeks.The primary endpoint was the change from baseline to week 6 in  Montgomery-Åsberg Depression Rating Scale (MADRS) score. 

Findings showed MDD patients with severe EDS who received solriamfetol had clinically meaningful and numerically greater improvements in MADRS total score, MADRS anhedonia subscale, MADRS remission (total score ≤10), Clinical Global Impression of Severity, Clinical Global Impression of Improvement, and Patient Global Impression of Improvement, compared with placebo. 

However, no meaningful differences were observed between the treatment and placebo groups in patients without severe EDS. In the overall study population, there was no statistically significant change on the MADRS total score vs placebo. 

Commenting on the results, Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics, said: “We are pleased to have completed the PARADIGM trial which provides data on the potential utility of solriamfetol in patients with MDD. The promising results with solriamfetol in MDD patients with severe EDS align with its known pharmacology and support its further evaluation in this potentially new indication.”

Full results from PARADIGM will be presented at a future medical meeting. According to the Company, another phase 3 trial in MDD patients with EDS will begin sometime this year. 

This article originally appeared on MPR