Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3): A Randomized Controlled Trial.

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Schweitzer PK, Rosenberg R, Zammit GK, Gotfried M, Chen D, Carter LP, Wang H, Lu Y, Black J, Malhotra A, Strohl KP

Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3): A Randomized Controlled Trial.

Am J Respir Crit Care Med. 2018 Dec 6. doi: 10.1164/rccm.201806-1100OC.

PubMed ID
30521757 [ View in PubMed
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Abstract

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: 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 pre-specified efficacy analyses. Co-primary 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; 5 participants experienced serious adverse events (2 [1.7%] placebo, 3 [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 registration available at www.clinicaltrials.gov, ID NCT02348606.

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