Dataset Information

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

ABSTRACT:

Objective

To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA).

Methods

Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/day [4 days]) or placebo for 7 days, before crossover to the other treatment paradigm. On Day 7 of each period, standardised on-road driving tests occurred (2 and 6 hours postdose). Standard deviation of lateral position (SDLP) was the primary endpoint.

Results

Solriamfetol significantly reduced SDLP at 2 (n = 34; least squares mean difference, -1.1 cm; 95% CI, -1.85, -0.32; p = 0.006) and 6 hours postdose (n = 32; least squares mean difference, -0.8 cm; 95% CI, -1.58, -0.03; p = 0.043). Two hours postdose, 4 placebo-treated and 1 solriamfetol-treated participants had incomplete driving tests; 6 hours postdose, 7 and 3 participants, respectively, had incomplete tests. Common treatment-emergent adverse events included headache, nausea, and insomnia.

Conclusions

Solriamfetol 300 mg/day significantly improved on-the-road driving performance in participants with EDS associated with OSA.

SUBMITTER: Vinckenbosch F

PROVIDER: S-EPMC9788130 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

Vinckenbosch Frederick F Asin Jerryll J de Vries Nicolaas N Vonk Patty E PE Donjacour Claire E H M CEHM Lammers Gert Jan GJ Overeem Sebastiaan S Janssen Hennie H Wang Grace G Chen Dan D Carter Lawrence P LP Zhou Kefei K Vermeeren Annemiek A Ramaekers Johannes G JG

Human psychopharmacology 20220528 6

<h4>Objective</h4>To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA).<h4>Methods</h4>Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/d ...[more]

PMID: 35633275

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Project description:Study objectivesExcessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea.MethodsEfficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation).ResultsA systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events.ConclusionsThe results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea.CitationRonnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.

Project description:Study objectivesSolriamfetol, 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.MethodsParticipants 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.ResultsSafety 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.ConclusionsLong-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 registrationRegistry: 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://clinicaltrials.gov/ct2/show/NCT02348632.CitationWeaver 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.

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:BackgroundExcessive daytime sleepiness (EDS) is a cardinal symptom of narcolepsy and affects many patients with obstructive sleep apnoea (OSA). EDS is associated with reduced quality of life, increased accident risk, and poor workplace performance. Given the impact of EDS, the ability to predict health-related utility from sleepiness is valuable for examining the cost effectiveness of novel treatments. The aim of this study was to examine the association between EDS and EQ-5D in patients with OSA and/or narcolepsy by modelling EQ-5D utility scores from Epworth Sleepiness Scale (ESS) scores.MethodsData were obtained from the Europe 2016/2017 National Health and Wellness Survey, an online, general population survey, designed to represent the age and gender composition of each country's adult population. Analyses included 2,348 patients self-reporting symptomatic and diagnosed OSA (n = 2,277), narcolepsy (n = 48), or both (n = 23). Multivariable models were used to examine ESS as a predictor of EQ-5D utility while adjusting for covariates of interest. Results were validated following the National Institute for Health and Care Excellence Decision Support Unit guidelines for predictive modelling.ResultsUtility decreased as EDS severity increased (no EDS: 0.711 ± 0.251, mild: 0.685 ± 0.261, moderate: 0.643 ± 0.268, severe: 0.559 ± 0.323). Whereas participants with only OSA or only narcolepsy did not differ in utility, those with both conditions had lower scores (0.685 ± 0.266 and 0.627 ± 0.325 vs. 0.439 ± 0.340, respectively). Piecewise linear regression identified a single breakpoint at ESS score of 11.29. In the final model, for each point increase in ESS score, the corresponding decrease in EQ-5D utility was larger among patients with ESS scores ≥ 12 compared to patients with ESS scores ≤ 11 (model slopes: -0.0131 vs. -0.0026, respectively). Findings from the validation sample confirmed these results.ConclusionsThis study demonstrates the impact of sleepiness on quality of life (QoL) and its negative impact irrespective of sleep condition (OSA or narcolepsy). The breakpoint identified is relatively consistent with the established ESS cutoff score ≥ 11, which demarcates pathological sleepiness. Furthermore, as EDS severity worsens (increases) on the ESS, the impact on QoL is greater.

Dataset Information

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

Objective

Methods

Results

Conclusions

Publications

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

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