1. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1421-1431. doi:
10.1164/rccm.201806-1100OC.

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

Schweitzer PK(1), Rosenberg R(2)(3), Zammit GK(4)(5), Gotfried M(6), Chen D(7),
Carter LP(7)(8), Wang H(7), Lu Y(7), Black J(7)(9), Malhotra A(10), Strohl
KP(11); TONES 3 Study Investigators.

Collaborators: Blackman A, George C, Shapiro C, Shapiro C, Benes H, Fietze I,
Mayer G, Young P, Lammers GJ, Ahmed M, Ajayi A, Andry J, Artal R, Bastani B,
Bogan R, Corser B, Drake C, Emsellem H, Erman M, Feldman N, Foldvary N, Gotfried 
M, Hudson J, Krahn L, Lorch D, Malhotra A, Maynard J, Mignot E, Neeb M, Ojile J, 
Perkins AT, Rosenberg R, Roy A, Sahota P, Sangal RB, Schreiber A, Schweitzer P,
Steele R, Stern T, Stern T, Stolz S, Strohl K, Swick T, Swick TJ, Thein SG,
Thomas R, Thorpy M, Weaver T, Wilks K, Winslow D, Wylie P, Zammit G, Zee P.

Author information: 
(1)1 Sleep Medicine and Research Center, St. Luke's Hospital, Chesterfield,
Missouri.
(2)2 NeuroTrials Research, Atlanta, Georgia.
(3)3 Atlanta School of Sleep Medicine, Atlanta, Georgia.
(4)4 Clinilabs Drug Development Corporation, New York, New York.
(5)5 Icahn School of Medicine at Mount Sinai, New York, New York.
(6)6 Pulmonary Associates, PA, Phoenix, Arizona.
(7)7 Jazz Pharmaceuticals, Palo Alto, California.
(8)8 University of Arkansas for Medical Sciences, Little Rock, Arkansas.
(9)9 Stanford Center for Sleep Sciences and Medicine, Palo Alto, California.
(10)10 University of California, San Diego, San Diego, California; and.
(11)11 Case Western Reserve University, Cleveland, Ohio.

Comment in
    Am J Respir Crit Care Med. 2019 Jun 1;199(11):1310-1311.

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 (Pā€‰<ā€‰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; Pā€‰<ā€‰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).

DOI: 10.1164/rccm.201806-1100OC 
PMCID: PMC6835071 [Available on 2020-06-01]
PMID: 30521757