Post Hoc Analysis of Solriamfetol Efficacy in Obstructive Sleep Apnea Patients with Excessive Daytime Sleepiness Stratified by Disease Severity.

introductionSolriamfetol, a dopamine and norepinephrine reuptake inhibitor, is indicated for the treatment of excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA). This study aims to evaluate the efficacy and safety profiles of solriamfetol across different severity levels of OSA via the post hoc analysis of a randomized clinical trial in a Chinese population.

methodsParticipants were assigned in a 1:1 ratio to either the placebo group or solriamfetol group (dose titrated up to 150 mg/day) for 12 consecutive weeks, with randomization stratified by adherence status to primary OSA therapy. The co-primary endpoints were defined as the changes of mean sleep latency measured by the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) scores from baseline to week 12 in the full analysis set. The efficacy and safety profiles of solriamfetol were analyzed across subgroups stratified by baseline apnea hypopnea index (AHI).

resultsAmong eligible patients for subgroup analysis, 42.5%, 34.5%, and 23% had baseline AHI < 5, 5 ≤ AHI < 30, and AHI ≥ 30, respectively. At week 12, solriamfetol treatment significantly prolonged MWT sleep latency relative to placebo across all AHI subgroups. The least squares (LS) mean differences (standard error) versus placebo were 12.133 (2.2239) min for the AHI < 5 subgroup (P < 0.0001), 12.676 (2.5363) min for the 5 ≤ AHI < 30 subgroup (P < 0.0001), and 10.935 (2.6023) min for the AHI ≥ 30 subgroup (P = 0.0001). In subgroups with baseline AHI < 5 and 5 ≤ AHI < 30, solriamfetol significantly reduced ESS scores vs. placebo (LS mean difference [SE] versus placebo, - 2.0 [0.95] and - 2.1 [1.01], P = 0.0404 and P = 0.0394, respectively). In the baseline AHI ≥ 30 subgroup, solriamfetol showed a tendency toward reduction in ESS scores compared with placebo, although the difference was not statistically significant (P = 0.2497). Meanwhile, solriamfetol was well tolerated, with the most common treatment-emergent adverse events (> 10% incidence in any treatment group) including upper respiratory tract infection, hyperuricemia, dizziness, and hypertension.

conclusionSolriamfetol showed good efficacy and tolerability regardless of OSA severity among Chinese OSA participants with EDS.

trial registrationThe parent study was registered at www.chinadrugtrials.org.cn with the trial number CTR20231397 on May 15, 2023.