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Am J Respir Crit Care Med. 2018 Dec 6. doi: 10.1164/rccm.201806-1100OC. [Epub ahead of print]

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

Author information

1
St. Luke's Hospital, Sleep Medicine and Research Center, Chesterfield, Missouri, United States ; paula.schweitzer@stlukes-stl.com.
2
NeuroTrials Research, Atlanta, Georgia, United States.
3
Atlanta School of Sleep Medicine, Atlanta, Georgia, United States.
4
Clinilabs Drug Development Corporation, New York, New York, United States.
5
Icahn School of Medicine at Mount Sinai, New York, New York, United States.
6
Pulmonary Associates, PA, Phoenix, Arizona, United States.
7
Jazz Pharmaceuticals, Palo Alto, California, United States.
8
Jazz Pharmaceuticals Inc, 17809, Palo Alto, California, United States.
9
University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States.
10
Stanford Center for Sleep Sciences and Medicine, Palo Alto, California, United States.
11
University of California, San Diego, Division of Pulmonary and Critical Care Medicine, San Diego, California, United States.
12
Case Western Reserve University, Cleveland, Ohio, United States.

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.

KEYWORDS:

JZP-110; TONES 3; excessive sleepiness; obstructive sleep apnea; solriamfetol

PMID:
30521757
DOI:
10.1164/rccm.201806-1100OC

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