Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy

Abstract

Study objectives: This post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment.

Methods: Participants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups.

Results: Common early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity.

Conclusions: Common early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://ichgcp.net/clinical-trials-registry/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA; URL: https://ichgcp.net/clinical-trials-registry/NCT02348606; Identifier: NCT02348606.

Citation: Rosenberg R, Thorpy MJ, Dauvilliers Y, et al. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022;18(1):235-244.

Keywords: JZP-110; OSA; Sunosi; apnea; lung; narcolepsy; safety; sleep; solriamfetol.

Conflict of interest statement

All authors have seen and approved the manuscript. This study was funded by Jazz Pharmaceuticals. Jazz Pharmaceuticals has worldwide development, manufacturing, and commercialization rights to solriamfetol, excluding certain jurisdictions in Asia. SK Biopharmaceuticals, the discoverer of the compound (also known as SKL-N05), maintains rights in 12 Asian markets, including Korea, China, and Japan. Under the direction of the authors Hannah Ritchie, PhD, and Jeannette Fee of Peloton Advantage, LLC, an OPEN Health company, provided medical writing and editorial support for this article, which was funded by Jazz Pharmaceuticals. R. Rosenberg has received consultancy fees from Eisai; honoraria from Merck; research funding from Jazz Pharmaceuticals, Merck, Actelion, Eisai, and Philips Respironics; and has served on the speakers’ bureau for Merck and as an advisory board member for Jazz Pharmaceuticals. M.J. Thorpy has received consultancy fees and served on advisory boards for Axsome, Balance Therapeutics, Avadel-Flamel, Harmony Biosciences, Jazz Pharmaceuticals, Suven Life Sciences, Takeda, Pharmaceuticals, and Eisai Pharmaceuticals. Y. Dauvilliers has received consultancy fees and/or honoraria and has been a speakers’ bureau member and/or an advisory board participant for UCB Pharma, Bioprojet, Theranexus, Idorsia, Takeda, Avadel, and Jazz Pharmaceuticals. P.K. Schweitzer has received consultancy fees from Jazz Pharmaceuticals. Her institution has received research funding from Jazz Pharmaceuticals, Apnimed, Balance Therapeutics, Avadel-Flamel, Harmony Biosciences, Inspire Medical Systems, and Suven Life Sciences. G.K. Zammit is an employee and shareholder of Clinilabs Drug Development Corporation; has ownership interest in the Sleep Disorders Institute and Home Sleep and Respiratory Care; has served as a consultant for Eisai Inc, Janssen Pharmaceuticals, Purdue, and Takeda; and has served on the speaker’s bureau for Merck. M. Gotfried has received honoraria from GSK and Boehringer Ingelheim; has received research funding from GSK, Boehringer Ingelheim, Sanofi, Jazz, and Eisai; and has served on the speakers’ bureau for Boehringer Ingelheim. S. Bujanover and B. Scheckner are employees of Jazz Pharmaceuticals, who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. A. Malhotra is funded by the National Institutes of Health. He has served as a principal investigator for a Jazz Pharmaceuticals study and reports income for medical education from Equillium, Corvus, and Livanova; ResMed gave a philanthropic donation to the University of California, San Diego, in support of a sleep center.

© 2022 American Academy of Sleep Medicine.

Figures

Figure 1. Incidence of new or increased-severity TEAEs for the most common early-onset TEAEs in participants in the OSA study.

All events depicted represent new-onset TEAEs with the exception of 1 event reported by a participant in the OSA study who had worsening of an existing TEAE of headache, which increased in severity from 1 (mild) at the beginning of the study to 2 (moderate) at the end of the study. Participants could list > 1 TEAE as reason for discontinuation (hence, the sum of those discontinuing due to individual TEAEs is greater than the overall discontinuations due to TEAEs). aPercentage of participants who discontinued due to AEs is based on the total number of participants who discontinued due to any common early-onset TEAE (n = 11). AE = adverse event, OSA = obstructive sleep apnea, TEAE = treatment-emergent adverse event.

Figure 2. Incidence of new or increased-severity TEAEs for the most common early-onset TEAEs in participants in the narcolepsy study.

All events depicted represent new-onset TEAEs. Participants could list > 1 TEAE as reason for discontinuation (hence, the sum of those discontinuing due to individual TEAEs is greater than the overall discontinuations due to TEAEs). aPercentage of participants who discontinued due to AEs is based on the total number of participants who discontinued due to any common early-onset TEAE (n = 1). AE = adverse event, TEAE = treatment-emergent adverse event.