A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Abstract

Objective Solriamfetol (JZP‐110) is a selective dopamine and norepinephrine reuptake inhibitor with wake‐promoting effects. This phase 3 study (NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy. Methods Patients with narcolepsy with mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score ≥10, and usual nightly sleep ≥6 hours were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Coprimary endpoints were change from baseline to week 12 in MWT and ESS. Improvement on the Patient Global Impression of Change (PGI‐C) was the key secondary endpoint. Results Safety and modified intention‐to‐treat populations included 236 and 231 patients, respectively. Solriamfetol 300 and 150 mg were positive on both coprimary endpoints. Least squares mean (standard error [SE]) changes from baseline were 12.3 (SE = 1.4) and 9.8 (SE = 1.3) minutes for solriamfetol 300 and 150 mg on the MWT, respectively, versus 2.1 (SE = 1.3) minutes for placebo, and −6.4 (SE = 0.7) for 300 mg and −5.4 (SE = 0.7) for 150 mg on the ESS versus −1.6 (SE = 0.7) for placebo (all p < 0.0001). At week 12, higher percentages of patients treated with solriamfetol 150 mg (78.2%) and 300 mg (84.7%) reported PGI‐C improvement relative to placebo (39.7%; both p < 0.0001). Adverse events ≥5% across all solriamfetol doses included headache (21.5%), nausea (10.7%), decreased appetite (10.7%), nasopharyngitis (9.0%), dry mouth (7.3%), and anxiety (5.1%). Interpretation Solriamfetol has the potential to be an important therapeutic option for the treatment of impaired wakefulness and excessive sleepiness in patients with narcolepsy. ANN NEUROL 2019;85:359–370.

Recently Approved and Upcoming Treatments for Narcolepsy

“…The efficacy and safety of solriamfetol were also evaluated in a phase III, 12-week randomised, double-blind, placebocontrolled trial from the TONES (Treatment of Obstructive Sleep Apnea and Narcolepsy Excessive Sleepiness) phase III programme-the TONES 2 study [31]. Adults with narcolepsy with or without cataplexy were randomly assigned to fixed doses of solriamfetol (75,150, 300 mg/day) or placebo.…”

“…Discontinuations due to AEs were reported for 7% of solriamfetol-treated participants in the short-term phase IIb study and for 5.1% of solriamfetol-treated participants (1.7%, 5.1% and 8.5% for the 75, 150 and 300 mg groups) in the short-term phase III study, compared with 4% and 2% in placebo-treated participants, respectively [30,31]. SAEs were reported for 4.5% (2/44) and 0.6% (1/177) of solriamfetol-treated participants in the phase IIb and III studies, respectively (no SAEs with placebo in either study) [30,31].…”

Update on the Treatment of Idiopathic Hypersomnia

“…With only a moderate effect of current stimulants in subpopulations of people with IH, the emergence of a new effective stimulant for the treatment of narcolepsy, solriamfetol [39], holds promise for the treatment of excessive daytime sleepiness in IH.…”

Single‐Dose Pharmacokinetics and Safety of Solriamfetol in Participants With Normal or Impaired Renal Function and With End‐Stage Renal Disease Requiring Hemodialysis

“…In phase 3 trials in patients with narcolepsy and OSA, solriamfetol demonstrated reductions in excessive daytime sleepiness measured on the patient-reported Epworth Sleepiness Scale, 3 and improvement in objective assessment of wakefulness using the Maintenance of Wakefulness Test, that were statistically significantly greater than placebo. [4][5][6] Significantly higher percentages of participants treated with solriamfetol in these trials also reported improvement on the Patient Global Improvement of Change scale relative to placebo at all evaluated time points.…”