New Drug Promising for Excessive Sleepiness

New Drug Promising for Excessive Sleepiness

TORONTO — Solriamfetol significantly improves wakefulness in patients with obstructive sleep apnea who suffer from excessive sleepiness, results from a phase 3 study show.

“This drug has immediate and significant effects on alertness during the day,” said Kingman Strohl, MD, program director of sleep medicine at University Hospitals Cleveland Medical Center. In addition, it decreases “the tendency for subjective sleepiness in people with excessive sleepiness.”

“It improves well-being without life-threatening adverse results,” he reported here at CHEST 2017.

Untreated sleep apnea is a serious problem, Dr Strohl told Medscape Medical News. Sleepiness can cause people to fall asleep at the wheel, for example, causing accidents, he pointed out.

In fact, previous studies have shown that 13% to 65% of patients with sleep apnea treated with continuous positive airway pressure (CPAP) still experience excessive sleepiness (Sleep. 2007;30:711-719; J Sleep Res. 2013;22:389-397; Eur Respir J. 2009;34:687-693).

Solriamfetol, also known as JZP-110, is a selective dopamine norepinephrine reuptake inhibitor under development by Jazz Pharmaceuticals. The neurotransmitter profile of solriamfetol is different than that of drugs currently on the market to treat excessive sleepiness, such as modafinil.

In their phase 3 trial, Dr Strohl and his colleagues assessed 459 patients with obstructive sleep apnea and excessive sleepiness. Study participants were randomly assigned to 12 weeks of treatment with one of four doses of solriamfetol — 300 mg, 150 mg, 75 mg, or 37.5 mg once daily — or to placebo.

Patients were at least 18 years of age and were using or had previously used therapy for primary sleep apnea, including CPAP, an oral appliance, or surgical intervention.

All patients met the International Classification of Sleep Disorders (ICSD)-3 criteria for obstructive sleep apnea; had a score on the Epworth Sleepiness Scale (ESS) of at least 10; had a mean sleep latency of less than 30 minutes on the first four trials of a five-trial, 40-minute Maintenance of Wakefulness Test (MWT); and had a usual nightly sleep time of at least 6 hours.

At week 12, the least square mean change from baseline on the Maintenance of Wakefulness Test, which measures how long a patient stays awake in a 40-minute period 5 times a day, was significantly higher with solriamfetol than with placebo.

Table 1. Change From Baseline in Maintenance of Wakefulness Test at 12 Weeks

Treatment Group	n	Least Square Mean Change (Minutes)	P Value
Solriamfetol 300 mg	115	13.0	<.0001
Solriamfetol 150 mg	116	11.0	<.0001
Solriamfetol 75 mg	58	9.1	<.0001
Solriamfetol 37.5 mg	56	4.7	<.5
Placebo	114	0.2	NS

 

Patient Global Impression of Change scores were significantly better after 12 weeks for all but the lowest dose of solriamfetol.

Table 2. Improvements in Patient Global Impression of Change

Treatment Group	Improvement, %	P Value
Solriamfetol 300 mg	88.7	<.0001
Solriamfetol 150 mg	89.7	<.0001
Solriamfetol 75 mg	72.4	<.05
Solriamfetol 37.5 mg	49.1	NS

 

Twenty-one patients in the 300 mg group discontinued treatment, as did 10 in the 150 mg, four in the 75 mg group, seven in the 37.5 mg group, and 13 in the placebo group.

The most common adverse events were headache (10.1%), nausea (7.9%), decreased appetite (7.6%), and anxiety (7.0%). These are also common adverse effects for similar drugs currently on the market.

It would be interesting to see a comparison of solriamfetol and the other alerting agents — modafinil or armodafinil — we use now, said Dwayne Henry, MD, from Our Lady of the Lake Physician Group in Baton Rouge, Louisiana.

“One of the side effects people complain about with modafinil is that it can cause a lot of headaches when you first start taking it,” he told Medscape Medical News.

Adverse effects might become the deciding factor for patients. “Whatever causes the least amount of irritation and whatever they get most benefit from, that’s what patients will use,” Dr Henry pointed out.

Smart Drugs

If solriamfetol is approved by the US Food and Drug Administration, doctors will have another nonaddictive option for patients with sleep disorders, and the off-label use common with other drugs with this profile will be opened up.

The medical community is aware that this drug is ripe for uptake in the “smart drug” market, alongside modafinil and armodafinil, which were approved for the treatment for narcolepsy and other sleep disorders in 1998.

Today, these drugs are widely used by professionals to stay awake and increase productivity, and are commonly prescribed to help shift workers and medical professionals who work long hours from falling asleep.

In addition, they have become popular as cognitive-performance enhancers, even for healthy people with above-average cognitive abilities, such as expert chess players, as previously reported by Medscape Medical News.

These drugs are considered pharmacologically distinct from schedule II prescription amphetamines and, because they are not considered to be addictive, they have less potential for abuse. Solriamfetol would likely fit that description.

This study was funded by Jazz Pharmaceuticals, the developer of solriamfetol. Dr Stohl is the principle investigator for Jazz Pharmaceuticals, and is a consultant, speaker, and advisory committee member for Inspire Medical Systems and Sommetrics. Dr Henry has disclosed no relevant financial relationships.

CHEST 2017: American College of Chest Physicians Annual Meeting: Abstract 4080. Presented October 29, 2017.

Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein

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