Solriamfetol Effective for Excessive Sleepiness in OSA, Narcolepsy

November 8, 2018

By Lorraine L. Janeczko

ATLANTA—The experimental drug solriamfetol appears to keep sleepy patients with narcolepsy or obstructive sleep apnea (OSA) awake and alert, according to an industry-sponsored trial.

The results were presented in a poster October 22 at the 2018 Annual Meeting of the American Neurological Association (ANA), in Atlanta.

"Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor that keeps people with narcolepsy or OSA awake and alert in the short term and in the long term," lead author Dr. Colin Shapiro of the University of Toronto, Canada, told Reuters Health in an interview.

"Providing these patients with an oral appliance or a CPAP (continuous positive airway pressure) machine is not sufficient to make sure that they can remain awake and alert enough to carry out activities of daily life, including operating machinery or driving a car, safely," he cautioned.

Dr. Shapiro and his colleagues enrolled patients with narcolepsy or OSA who had completed an earlier solriamfetol study, beginning with a two-week titration phase followed by an open-label maintenance phase of up to 50 weeks. After participants were treated for six months, the researchers conducted a two-week placebo-controlled randomized withdrawal phase.

The research team evaluated participants' change in Epworth Sleepiness Scale (ESS) score from the beginning to the end of the randomized withdrawal phase, and they assessed the Patient and Clinician Global Impression of Change (PGI-C and CGI-C) scores.

Overall, 643 participants were included in the safety population of the open-label phase; of these, 226 had narcolepsy and 417 had OSA. From this group, 280 participants were assigned to the efficacy population in the randomized withdrawal phase: 141 received placebo and 139 received solriamfetol.

At six months, patients who received placebo in the randomized withdrawal phase showed an increase of 5.3 points in the ESS, compared with a 1.6-point increase for those on solriamfetol (P<0.0001).

PGI-C and CGI-C scores showed that significantly more patients randomized to placebo were worse at the end of the withdrawal compared with patients in the solriamfetol group.

At one year, decreased mean ESS scores and improved PGI-C and CGI-C scores were maintained after open-label treatment with solriamfetol in the overall safety population.

Overall, 27 (4.2%) participants experienced one or more serious treatment-emergent adverse events with solriamfetol, including decreased appetite, anxiety, dry mouth, insomnia, nasopharyngitis, nausea and headache. One death, due to sepsis in an immunosuppressed participant on solriamfetol, was considered unrelated to the study drug.

"The study design was complicated, but it produced very clear results showing that solriamfetol keeps people awake and alert," Dr. Shapiro said.

Dr. M. Elizabeth Ross, director of the Center for Neurogenetics at Weill Cornell Medicine in New York City, said by email, "Solriamfetol is an investigational drug for the treatment of excessive sleepiness. It selectively blocks the reuptake of dopamine and norepinephrine back into neurons after they have released these transmitters at the synapse, thereby increasing the activity of neurons that keep us awake."

"Pharmacologic studies indicate that this selective reuptake action differs from drugs currently in use for excessive sleepiness and may be a significant alternative," noted Dr. Ross, who is the scientific program advisory committee chair of the American Neurological Association but was not involved in the study.

"The purpose of this report was to examine the effectiveness of the drug when used in a steady dose for nearly one year," she noted. "While this is an interesting study, one must keep in mind that it is often difficult to obtain completely objective information - the ultimate goal of a blinded study - since subjects who were switched to a placebo may have realized that they were no longer receiving the drug if they noticed changes in side effects, such as dry mouth. Nevertheless, the multicenter nature of the trial supports the reliability of the assessment."

Jazz Pharmaceuticals funded the study.

SOURCE: https://bit.ly/2DpJ6qO

American Neurological Association Annual Meeting 2018.

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