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Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea.

ABSTRACT: STUDY OBJECTIVES:To evaluate long-term safety and maintenance of efficacy of solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea (OSA). METHODS:Participants with narcolepsy or OSA who completed a prior solriamfetol study were eligible. A 2-week titration period was followed by a maintenance phase (up to 50 weeks). Efficacy was assessed by Epworth Sleepiness Scale (ESS) and Patient and Clinical Global Impression of Change (PGI-C and CGI-C, respectively). After approximately 6 months of treatment, a subgroup entered a 2-week placebo-controlled randomized withdrawal (RW) phase. Change in ESS from beginning to end of the RW phase was the primary endpoint; PGI-C and CGI-C were secondary endpoints. Safety was assessed throughout the study. RESULTS:In the maintenance phase, solriamfetol-treated participants demonstrated clinically meaningful improvements on ESS, PGI-C, and CGI-C. In the RW phase, least squares mean change on ESS was 1.6 in participants continuing solriamfetol versus 5.3 in participants switched to placebo (p < .0001). For both secondary endpoints, higher percentages of participants receiving placebo were reported as worse at the end of the RW phase versus solriamfetol (p < .0001). Common treatment-emergent adverse events (TEAEs) with solriamfetol were headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection; 27 (4.2%) participants experienced at least one serious TEAE, and 61 (9.5%) withdrew because of TEAEs. CONCLUSIONS:This study demonstrated long-term maintenance of efficacy of solriamfetol under open-label and double-blind, placebo-controlled conditions. Safety profile of solriamfetol was consistent with previous 12-week studies; no new safety concerns were identified. TRIAL REGISTRATION:NCT02348632.

SUBMITTER: Malhotra A

PROVIDER: S-EPMC7315408 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea.

Malhotra Atul A Shapiro Colin C Pepin Jean-Louis JL Hedner Jan J Ahmed Mansoor M Foldvary-Schaefer Nancy N Strollo Patrick J PJ Mayer Geert G Sarmiento Kathleen K Baladi Michelle M Chandler Patricia P Lee Lawrence L Schwab Richard R

Sleep 20200201 2

<h4>Study objectives</h4>To evaluate long-term safety and maintenance of efficacy of solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea (OSA).<h4>Methods</h4>Participants with narcolepsy or OSA who completed a prior solriamfetol study were eligible. A 2-week titration period was followed by a maintenance phase (up to 50 weeks). Efficacy was assessed by Epworth Sleepiness Scale (ESS) and Patient and Clinical Global Impression of Change (PGI-C and CGI ...[more]

PMID: 31691827

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Project description:Rationale: Primary treatment of obstructive sleep apnea can be accompanied by a persistence of excessive sleepiness despite adherence. Furthermore, effectiveness of sleep apnea treatment is limited by poor adherence. Currently available pharmacologic options for the treatment of sleepiness in this population are limited. Objectives: To evaluate the efficacy and safety of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, for the treatment of excessive sleepiness in participants with obstructive sleep apnea with current or prior sleep apnea treatment. Methods: This was a double-blind, randomized, placebo-controlled, parallel-group, 12-week trial comparing solriamfetol, 37.5, 75, 150, and 300 mg, with placebo. Measurements and Main Results: Of 476 randomized participants, 459 were included in the prespecified efficacy analyses. Coprimary endpoints (Maintenance of Wakefulness Test sleep latency and Epworth Sleepiness Scale score) were met at all solriamfetol doses (P < 0.05), with dose-dependent effects observed at Week 1 maintained over the study duration. All doses except 37.5 mg resulted in higher percentages of participants reporting improvement on Patient Global Impression of Change (key secondary endpoint; P < 0.05). Adverse events were reported in 47.9% of placebo- and 67.9% of solriamfetol-treated participants; five participants experienced serious adverse events (two [1.7%] placebo, three [0.8%] solriamfetol); none were deemed related to study drug. The most common adverse events with solriamfetol were headache (10.1%), nausea (7.9%), decreased appetite (7.6%), anxiety (7.0%), and nasopharyngitis (5.1%). Conclusions: Solriamfetol significantly increased wakefulness and reduced sleepiness in participants with obstructive sleep apnea and excessive sleepiness; most adverse events were mild or moderate in severity. Clinical trial registered with www.clinicaltrials.gov (NCT02348606) and www.eudract.ema.europa.eu (EudraCT 2014-005514-31).

Project description:Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0-3 months, then it was 13-19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

Project description:BACKGROUND:Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient's health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. METHODS:Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. RESULTS:Over three-fifths of study participants (n?=?26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n?=?14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n?=?1, 2%) or were treatment naïve (n?=?1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ?1?year, with an average duration of 11.4 (median 8.0, range 1-37) years before seeking medical attention. Several (n?=?7, 32%) considered their symptoms to be "normal," rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n?=?20, 67%); their own concern about particular symptoms (n?=?7, 23%); and/or falling asleep while driving (n?=?5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n?=?40, 95%); work productivity (n?=?38, 90%); daily life functioning (n?=?39, 93%); cognition (n?=?38, 90%); social life/relationships (n?=?37, 88%); and emotions (n?=?30, 71%). CONCLUSIONS:Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

Dataset Information

Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea.

Publications

Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea.

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