In Phase 3 Study, Some Solriamfetol Doses Improve Work and Activity Functioning for People with Narcolepsy

The selective dopamine/norepinephrine reuptake inhibitor improved impairment at work at 150 mg and activity impairment outside of work at 150 mg and 300 mg.

In her practice at The Center for Sleep & Wake Disorders in Chevy Chase, Md, neurologist and sleep specialist Helene Emsellem, MD, regularly sees patients with narcolepsy who need therapies beyond those commercially available today. Some have trouble being fully alert for typical daytime activities, such as working or socializing with friends. That’s why Emsellem, director of the center, became an investigator for a phase 3 study of solriamfetol—a selective dopamine/norepinephrine reuptake inhibitor with wake-promoting effects.

Earlier this year, the US Food and Drug Administration (FDA) accepted for filing with standard review Jazz Pharmaceutical’s New Drug Application (NDA) seeking marketing approval for solriamfetol (also known as JZP-110) for the treatment of excessive sleepiness in adult patients with narcolepsy or obstructive sleep apnea. An abstract coauthored by Emsellem based on a 12-week phase 3 study in narcolepsy patients was supported by Jazz and presented at SLEEP 2018; Emsellem continues to work on a 9-month open label extension study.

In general, Emsellem says, one daily dose of the investigational drug given upon awakening helped narcolepsy patients function better during the day while not interfering with their sleep at night. “My clinical impression from patients who felt they responded to this drug was that it helped their day go more smoothly, in terms of their ability to get their jobs done as well as their ability to be social with their families and do things outside of work. Of course it was a double blind study so this is my personal impression from the patients’ reports,” she says.

This study tried 75 mg, 150 mg, and 300 mg (as well as placebo) dosing. Statistically significant results were found at 150 mg and 300 mg in some quality of life and work productivity measures. The 12-week data showed improved functioning and health-related quality of life at 300 mg, particularly on the vitality (all doses) and role physical domains.

Significant improvement in activity impairment outside of work was seen at 150 mg and 300 mg dosing. Significant improvement in impairment at work was seen at 150 mg only. Patients reported “less time getting up and walking to coffee machines and getting up and pacing the office to stay awake and less inadvertent nap time at their desks,” Emsellem says. One response often heard by patients when interviewed, as characterized by Emsellem, was, “My day just goes easier and I get more done.”

Emsellem says it was surprising that only the 150 mg dose—and not also the higher 300 mg dose—reached statistical significance in improving impairment while working (impairment while working is also known as “presenteeism”). She suspects two possible explanations. One, the patients who were randomized to the 300 mg happened to have a mean starting impairment of 48.4%, while the patients who were randomized to the 150 mg group happened to have a mean starting impairment of 60.7%—the 12.3% difference could have had clinical significance. Second, the “n” [number of participants] in the sub-groups was small (n=34 to 59) so it may have been underpowered to measure whether there was improvement.

Also surprising to Emsellem is that health-related quality of life domains such as emotional and social functioning also did not show statistical significance. “However, you have to interpret this with caution because [the Short Form Health Survey version 2 (SF-36 V2)] is a general scale and it is not asking questions about sleep disturbances. So it’s not targeted to answer that question, Emsellem says, adding that the short time base of a 12-week study may not have been enough time for significant changes in the mental component summary score. “We are looking forward to seeing the 12-month open label data to see whether we’ll see those trends,” she says.

The study did include the FOSQ-10, which is a sleep-specific instrument, and does show changes statistically at 300 mg. The improvement of solriamfetol was clinically relevant as it exceeded the minimally important difference level of 1.7 to 2.0 that was presented by Terri Weaver, PhD, RN, FAAN, et al, at SLEEP 2009.

Sree Roy is editor of Sleep Review.

from Sleep Review http://www.sleepreviewmag.com/2018/06/phase-3-solriamfetol-work-activity-function/

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