Solriamfetol Improves Wakefulness in Phase 3 Trial of Obstructive Sleep Apnea

A multicenter, randomized, double-blind, placebo-controlled phase 3 trial (NCT06103825) conducted across multiple centers in China found that treatment with solriamfetol (Sunosi; Axsome Therapeutics) significantly improved wakefulness and reduced excessive daytime sleepiness (EDS) in adults with obstructive sleep apnea (OSA). The therapy also demonstrated an acceptable safety and tolerability profile over 12 weeks of treatment.¹

Efficacy Outcomes

Study author Hanrong Cheng, PhD, deputy director of the Department of Sleep Medicine at Shenzhen People's Hospital in Guandong, China, and colleagues observed that at week 12, mean Maintenance of Wakeful Test (MWT) sleep latency increased significantly in the solriamfetol group relative to placebo, with a least-squares mean difference of 11.77 minutes (95% CI, 8.99–14.55; P < .0001). In addition, a greater proportion of patients receiving solriamfetol achieved normalized wakefulness levels, defined as an MWT latency of at least 19.4 minutes.¹

Subjective sleepiness also improved with treatment. Patients receiving solriamfetol demonstrated a significantly greater reduction in Epworth Sleepiness Scale (ESS) score compared with placebo, with a between-group difference of –1.8 points (P = .0017) at week 12.

Patient-reported outcomes similarly favored solriamfetol. By week 12, 89.1% of patients in the treatment group reported improvement on the PGI-C scale compared with 77.0% of those receiving placebo (P = .0221).¹ The investigators noted that improvements in wakefulness were observed as early as week 2 and were maintained throughout the 12-week treatment period.

“Our findings demonstrate robust improvements in wakefulness and reductions in excessive sleepiness among patients with OSA treated with solriamfetol,” the authors wrote, adding that the results were consistent with previous clinical trials conducted in Western populations.¹

Study Design

The trial evaluated the efficacy and safety of solriamfetol in patients with OSA-associated EDS in China.¹ A total of 204 adults aged 18 to 75 years were randomly assigned in a 1:1 ratio to receive flexible-dose solriamfetol (75–150 mg once daily) or placebo for 12 weeks.

Eligible participants had a mean MWT sleep latency of less than 30 minutes and an Epworth Sleepiness Scale (ESS) score of at least 10 at baseline. Patients with other conditions that could cause excessive daytime sleepiness were excluded from the trial. The co-primary endpoints were changes from baseline to week 12 in mean sleep latency on the MWT and ESS score, with secondary outcomes that included the Patient Global Impression of Change (PGI-C) scale.

Of the 204 participants randomized, 192 completed the study, with 96 participants in each treatment arm. Baseline demographic characteristics were similar between groups, with a mean age of approximately 46 years and a mean body mass index of about 27.5 kg/m.¹

Safety Findings

Solriamfetol was generally well tolerated during the study period, with adverse events mild to moderate in severity. Treatment-emergent adverse events (TEAEs) were reported in 82.4% of patients receiving solriamfetol and 65.7% of those receiving placebo. Overall, the most commonly reported TEAEs in the solriamfetol group included upper respiratory tract infection, dizziness, hyperuricemia, hypertension, hyperlipidemia, and elevated creatine phosphokinase levels. Serious AEs were rare, with one event reported in each treatment group.

Investigators also observed transient increases in blood pressure and pulse rate following solriamfetol dosing, though these changes were not sustained and did not result in clinically significant safety concerns.¹

Clinical Context

OSA is the most common sleep-related breathing disorder and is frequently associated with excessive daytime sleepiness, a symptom that can impair cognitive function, productivity, and quality of life. Although continuous positive airway pressure (CPAP) therapy remains the standard treatment for OSA, many patients continue to experience residual daytime sleepiness despite adequate management of airway obstruction.²

Residual excessive daytime sleepiness remains a significant clinical challenge in patients with OSA, even among those receiving standard therapies such as CPAP. Wake-promoting agents—including modafinil, armodafinil, and solriamfetol—have therefore emerged as adjunctive pharmacologic options for managing persistent symptoms.²

However, treatment options for EDS associated with OSA remain limited in China, where modafinil is currently the only approved pharmacologic therapy for this indication.¹

Conclusions

Investigators concluded that solriamfetol produced significant improvements in wakefulness, reduced subjective sleepiness, and demonstrated a manageable safety profile in patients with OSA-related EDS in China.

“These findings support solriamfetol as a potential therapeutic option for managing excessive sleepiness associated with obstructive sleep apnea,” the authors noted.¹

REFERENCES
1. Cheng H, Deng L, Meng Z, et al. Efficacy and Safety of Solriamfetol on Excessive Daytime Sleepiness Associated with Obstructive Sleep Apnea in China: A Phase 3, Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial. CNS Drugs. 2026;40(1):83-98. doi:10.1007/s40263-025-01232-1
2. Malhotra A, Shapiro C, Pepin JL, et al. Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea. Sleep. 2020;43(2):zsz220. doi:10.1093/sleep/zsz220