Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea

Abstract

Study objectives: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the United States and European Union for excessive daytime sleepiness in adults with narcolepsy (75-150 mg/day) or obstructive sleep apnea (OSA; 37.5-150 mg/day). In 12-week studies, solriamfetol was associated with improvements in quality of life in participants with narcolepsy or OSA. These analyses evaluated the long-term effects of solriamfetol on quality of life.

Methods: Participants with narcolepsy or OSA who completed previous solriamfetol studies were eligible. A 2-week titration was followed by a maintenance phase ≤ 50 weeks (stable doses: 75, 150, or 300 mg/day). Quality of life assessments included Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-Item Short Form Health Survey version 2. Mean (standard deviation) changes from baseline to end of study were evaluated. Data were summarized descriptively. Adverse events were assessed.

Results: Safety population comprised 643 participants (417 OSA, 226 narcolepsy). Solriamfetol improved Functional Outcomes of Sleep Questionnaire short version Total scores (mean change [standard deviation], 3.7 [3.0]) and 36-Item Short Form Health Survey version 2 Physical and Mental Component Summary scores (3.1 [6.9] and 4.3 [8.4], respectively); improvements were sustained throughout treatment. On Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, solriamfetol reduced (improved) % presenteeism, % overall work impairment, and % activity impairment by a minimum of 25%. Common adverse events (≥ 5%): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection.

Conclusions: Long-term solriamfetol treatment was associated with clinically meaningful, sustained improvements in functional status, work productivity, and quality of life for up to 52 weeks. Adverse events were similar between narcolepsy and OSA.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects with Narcolepsy or OSA; Identifier: NCT02348632; URL: https://ichgcp.net/clinical-trials-registry/NCT02348632.

Citation: Weaver TE, Pepin J-L, Schwab R, et al. Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. J Clin Sleep Med. 2021;17(10):1995-2007.

Keywords: HRQoL; JZP-110; OSA; Sunosi; functional status; narcolepsy; quality of life; sleep disorders; work productivity.

Conflict of interest statement

All authors have seen and approved this 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. T.E. Weaver has received royalties for use of the FOSQ from Philips Respironics, ResMed, ResMed Germany, Nyxoah, Jazz Pharmaceuticals, Cook Medical, RWS, Stratevi, WCG MedAvante Prophase, Bayer AG, LivaNova, and Evidation Health. J.-L. Pepin has received lecture fees or conference traveling grants from ResMed, Perimetre, Philips, Fisher and Paykel, AstraZeneca, Jazz Pharmaceuticals, Agiradom, and Teva and has received unrestricted research funding from ResMed, Philips, GlaxoSmithKline, Bioprojet, Fondation de la Recherche Medicale (Foundation for Medical Research), Direction de la Recherche Clinique du CHU de Grenoble (Research Branch Clinic CHU de Grenoble), and fond de dotation “Agir pour les Maladies Chroniques” (endowment fund “Acting for Chronic Diseases”). R. Schwab has received research funding from the National Institutes of Health and Inspire Medical Systems, ResMed, and CryOSA. He has received income from Merck for medical education and royalties from Up-To-Date. C. Shapiro has received research funding from the National Institutes of Health and the Canadian Institutes of Health Research and has served on the speakers’ bureau for Jazz Pharmaceuticals. J. Hedner has served on the speakers’ bureaus for AstraZeneca, Philips Respironics, Itamar Medical, and BresoTec and serves as a board member for Cereus Pharma. N. Foldvary-Schaefer served as a consultant for Jazz Pharmaceuticals and receives research support from Jazz Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceuticals. P.J. Strollo Jr has received consultancy fees and honoraria from Inspire Medical Systems, ResMed, Philips-Respironics, Emmi Solutions, Jazz Pharmaceuticals, and Itamar; has received research funding from the National Institutes of Health and Inspire Medical Systems; and has a provisional patent for positive airway pressure with integrated oxygen. G. Mayer has served on the speakers’ bureau for UCB Pharma, Jazz Pharmaceuticals, and Janssen Pharma and is a board member of the International REM Sleep Behavior Study Group. K. Sarmiento serves on advisory boards for Jazz Pharmaceuticals and has received research funding from ResMed. M. Baladi is an employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. M. Bron and L. Lee are former employees of Jazz Pharmaceuticals who, in the course of this employment, received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. P. Chandler is an employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. A. Malhotra has served as a principal investigator for a Jazz Pharmaceuticals study but receives no personal income from Jazz Pharmaceuticals. He received income from Livanova, Equilium, and Corvus for medical education on topics unrelated to this article. ResMed gave a philanthropic donation to the University of California San Diego in support of a sleep center. M. Ahmed reports no conflicts of interest.

© 2021 American Academy of Sleep Medicine.

Figures

Figure 1. Study design.a

aStudy design for Group A only; Group B was similar except total duration was 52 weeks. Adapted from Malhotra et al. RW = randomized withdrawal.

Figure 2. Participant disposition.

aA total of 226 from Group A, 56 from Group B. Adapted from Malhotra et al. mITT = modified intent-to-treat, OSA = obstructive sleep apnea, RW = randomized withdrawal.

Figure 3. Change in FOSQ-10 Total score during the open-label phase.a

aGroup A only. A positive change from baseline indicates improvement. FOSQ-10 = Functional Outcomes of Sleep Questionnaire short version, OSA = obstructive sleep apnea, SD = standard deviation.

Figure 4. Change in FOSQ-10 total score during the randomized withdrawal phase.a

aGroups A and B combined. The end of the RW phase was scheduled at week 29 for Group A and week 28 for Group B. FOSQ-10 = Functional Outcomes of Sleep Questionnaire short version, OSA = obstructive sleep apnea, RW = randomized withdrawal, SD = standard deviation.

Figure 5. Percentage of participants with FOSQ-10 total scores in normal range (≥ 17.9).a

aGroup A only. Percentages are based on the number of participants with no missing data at a specific visit. FOSQ-10 = Functional Outcomes of Sleep Questionnaire short version, OSA = obstructive sleep apnea.

Figure 6. Change in EDS-related work/activity impairment on the WPAI:SHP.a

(A) Absenteeism (work time missed). (B) Presenteeism (impairment while working). (C) Overall work impairment. (D) Activity impairment. aGroup A only. bRegular daily activities other than work at a job. A negative change from baseline indicates improvement. EDS = excessive daytime sleepiness, OSA = obstructive sleep apnea, SD = standard deviation, WPAI:SHP = Work Productivity and Activity Impairment Questionnaire: Specific Health Problem.

Figure 7. Change in general HRQoL scores on the SF-36v2.a

(A) Physical and Mental Component Summary scores. (B) Subscale scores. (C) Vitality domain. aGroup A only. A positive change from baseline indicates improvement. HRQoL = health-related quality of life, OSA = obstructive sleep apnea, SD = standard deviation, SF-36v2 = Short Form Health Survey version 2.