Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea

Abstract

Study objectives: To evaluate the clinical relevance of solriamfetol in treating excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea (OSA).

Methods: This posthoc analysis includes data from two 12-week, randomized phase 3 studies in participants with narcolepsy or OSA treated with once-daily placebo or solriamfetol 37.5 mg (OSA only), 75 mg, 150 mg, or 300 mg. Excessive daytime sleepiness was assessed with the Epworth Sleepiness Scale (ESS) at baseline and at week 12. Cumulative distribution function plots were generated using a last-observation-carried-forward approach to determine the percentage of participants who achieved ESS scores ≤ 10, within the normal range, and the percentage who achieved a reduction (improvement) in ESS ≥ 25% relative to baseline. Safety was also assessed.

Results: In narcolepsy (n = 231), 30.5%-49.2% of participants treated with solriamfetol (across doses) reported ESS scores ≤ 10 and 44.1%-62.7% achieved a ≥ 25% decrease from baseline in ESS scores at week 12, compared with 15.5% and 27.6%, respectively, of placebo recipients. In OSA (n = 459), 51.8%-73.0% of participants treated with solriamfetol (across doses) reported ESS scores ≤ 10 and 50.0%-81.9% achieved a ≥ 25% decrease from baseline in ESS scores at week 12, compared with 37.7% and 36.8%, respectively, of placebo recipients. Results were generally dose-dependent, with more responders at higher solriamfetol doses. Common treatment-emergent adverse events (≥ 5% of solriamfetol recipients in either study) were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety.

Conclusions: A greater percentage of participants treated with solriamfetol achieved normal ESS scores (≤ 10) or clinically meaningful improvements on the ESS compared with those receiving placebo. The safety profile was similar between participants with narcolepsy and those with OSA.

Clinical trial registrations: Registry: ClinicalTrials.gov. Names: TONES 2 and TONES 3. URLs: https://www.clinicaltrials.gov/ct2/show/NCT02348593 and https://www.clinicaltrials.gov/ct2/show/NCT02348606. Identifiers: NCT02348593, NCT02348606. Registry: European Union Drug Regulating Authorities Clinical Trials. Names: TONES 2 and TONES 3. URL: https://www.eudract.ema.europa.eu. Identifiers: EudraCT 2014-005487-15, EudraCT 2014-005514-31.

Keywords: JZP-110; OSA; Sunosi; clinical relevance; hypersomnolence; narcolepsy; normalization; responder; self-report; sleepiness.

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, and 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. Baladi is an employee and M. Bron is a former employee of Jazz Pharmaceuticals who, in the course of their employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc.

© 2021 American Academy of Sleep Medicine.

Figures

Figure 1. Cumulative distribution function plots: narcolepsy.

Cumulative distribution function plots for participants with narcolepsy at week 12 (mITT populations): percentages of participants with ESS score ≤ 10 (A) and with ≥ 25% decrease from baseline in ESS score (B). Vertical gray dashed lines represent thresholds for clinically meaningful improvement (ie, ESS ≤ 10 or > 25% decrease from baseline scores). Horizontal dashed lines indicate value at which each group reached the threshold (ie, percentage of participants who achieved each threshold). ESS = Epworth Sleepiness Scale, mITT = modified intent-to-treat.

Figure 2. Cumulative distribution function plots: OSA.

Cumulative distribution function plots for participants with OSA at week 12 (mITT populations): percentages of participants with ESS score ≤ 10 (A) and with ≥ 25% decrease from baseline in ESS score (B). Vertical gray dashed lines represent threshold for clinically meaningful improvement (ie, ESS ≤ 10 or > 25% decrease from baseline scores). Horizontal dashed lines indicate value at which each group reached the threshold (ie, the percentage of participants who achieved each threshold). ESS = Epworth Sleepiness Scale, mITT = modified intent-to-treat, OSA = obstructive sleep apnea.