TY - JOUR
T1 - 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
AU - Rosenberg, Russell
AU - Thorpy, Michael J.
AU - Dauvilliers, Yves
AU - Schweitzer, Paula K.
AU - Zammit, Gary
AU - Gotfried, Mark
AU - Bujanover, Shay
AU - Scheckner, Brian
AU - Malhotra, Atul
N1 - Funding Information:
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 Liva-nova; ResMed gave a philanthropic donation to the University of California, San Diego, in support of a sleep center.
Publisher Copyright:
© 2022 American Academy of Sleep Medicine. All rights reserved.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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://clinicaltrials.gov/ct2/show/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://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606.
AB - 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://clinicaltrials.gov/ct2/show/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://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606.
KW - JZP-110
KW - OSA
KW - Sunosi
KW - apnea
KW - lung
KW - narcolepsy
KW - safety
KW - sleep
KW - solriamfetol
UR - http://www.scopus.com/inward/record.url?scp=85114110545&partnerID=8YFLogxK
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U2 - 10.5664/jcsm.9550
DO - 10.5664/jcsm.9550
M3 - Article
C2 - 34283019
AN - SCOPUS:85114110545
SN - 1550-9389
VL - 18
SP - 235
EP - 244
JO - Journal of Clinical Sleep Medicine
JF - Journal of Clinical Sleep Medicine
IS - 1
ER -