In a phase 3 study, solriamfetol demonstrated both safety and efficacy in patients with narcolepsy. The selective dopamine and norepinephrine reuptake inhibitor has a mechanism of action different from other wake-promoting agents.
In a phase 3 study, solriamfetol demonstrated both safety and efficacy in patients with narcolepsy, according to results published in Annals of Neurology. The selective dopamine and norepinephrine reuptake inhibitor has a mechanism of action different from other wake-promoting agents.
The double-blind, randomized, placebo-controlled, international trial included patients with narcolepsy type 1 or type 2, which are distinguished by the presence of cataplexy in type 1. Two main symptoms of narcolepsy, excessive sleepiness (ES) and impaired daytime wakefulness, were examined as primary end points via changes in the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) of sleep latency, respectively.
Eligible patients were randomized 1:1:1:1 to receive 75, 150, or 300 mg of solriamfetol per day or placebo once daily for 12 weeks. The end points were measured at both baseline and week 12. A key secondary end point was the percentage of patients who reported improvement on the Patient Global Impression of Change (PGI-C) scale, which categorized the improvements perceived by patients as “minimal,” “much,” or “very much” improved. Patients were also asked about adverse events (AEs) to evaluate safety and tolerability.
Of the 236 patients who received at least 1 dose of study drug (solriamfetol or placebo), about two-thirds (64.4%) were rated as moderately or markedly ill and half (50.8%) had cataplexy. The study groups were similar in demographic and clinical characteristics. The rate of trial discontinuation was highest in the group receiving 300 mg of solriamfetol, most commonly due to lack of efficacy or occurrence of AEs.
Both the 150- and 300-mg doses of solriamfetol met the coprimary end points of significant improvement from baseline on the ESS and the MWT, as well as the secondary end point of percentage of patients reporting improvement on the PGI-C (all P <.0001). From baseline to week 12, mean sleep latency increased by 9.8 and 12.3 minutes in the 150- and 300-mg groups, respectively, compared with 2.1 minutes for the placebo group (both P <.0001). Although the 75-mg dose group reported an increase of 4.7 minutes, the difference compared with placebo was not significant (P = .1595).
Mean ESS scores decreased by 3.8, 5.4, and 6.4 points in the 75-, 150-, and 300-mg solriamfetol groups, respectively, compared with a mean decrease of 1.6 points for placebo (P = .0211 for 75 mg; P <.0001 for 150 and 300 mg).
There was a solriamfetol dose-dependent pattern of increases in the patients reporting improvement in their overall condition, with 67.8%, 78.2%, and 84.7% in the 3 treatment groups (75, 150, and 300 mg, respectively) reporting improvement compared with 39.7% in the placebo group.
The incidence of any AE was higher in the groups receiving solriamfetol than placebo, and more patients in the 150- and 300-mg groups discontinued treatment due to AEs than with placebo. The most common AEs in the combined groups receiving solriamfetol were headache (21.5%), nausea (10.7%), and decreased appetite (10.7%). No serious AEs were reported.
The investigators noted that improvements in both primary end points were observed as early as week 1 of the trial and continued in the 150- and 300-mg groups through the 12-week study duration. The MWT improvements seen in the study surpassed those reported with modafinil, a dopamine reuptake inhibitor commonly used to treat ES in narcolepsy.
“In conclusion, once-daily oral dosing of solriamfetol 150 and 300 mg resulted in major improvements in wakefulness and reductions in ES associated with narcolepsy together with patient- and clinician-reported global improvements,” they wrote. “These results demonstrate that solriamfetol represents an important potential future therapeutic option for the treatment of impaired wakefulness and ES in individuals with narcolepsy.”
The study was supported by Jazz Pharmaceuticals, maker of solriamfetol.
Thorpy MJ, Shapiro C, Mayer G, et al. A randomized study of solriamfetol for excessive sleepiness in narcolepsy [published online January 29, 2019]. Ann Neurol. doi: 10.1002/ana.25423.