A Phase 1 safety study evaluating the impact of bedtime administration with lemborexant on driving performance the following morning has been published, announced Eisai Co Ltd and Purdue Pharma LP. The study, which met its primary endpoint, showed no statistically significant next-day impairment of driving performance in healthy adult and elderly volunteers compared to placebo. The study was recently published online by the peer-reviewed journal SLEEP, the official journal of the Sleep Research Society.
Lemborexant is an investigational agent being studied for the treatment of insomnia, a sleep-wake disorder. Lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli. Eisai and Purdue Pharma have conducted two Phase 3 safety and efficacy studies of lemborexant, which supported the New Drug Application submitted to the US Food and Drug Administration (FDA) on December 27, 2018.
The study evaluated next-morning effects of lemborexant 2.5, 5, and 10 mg doses compared with placebo, on driving performance after single and repeated bedtime use in healthy adult and elderly volunteers, 21 years and older (n=48). Zopiclone 7.5 mg was selected as an active control to demonstrate assay sensitivity versus placebo. Driving performance was assessed by standard deviation of lateral position (SDLP), an index of road tracking error or “weaving” (measured in centimeters), during an on-road driving test conducted on the mornings following the first and last dose of study medication.
At all doses evaluated, lemborexant showed no clinically meaningful or statistically significant impairment of driving performance after either single (on the morning of Day 2) or multiple (on the morning of Day 9) dose administration compared to placebo. In contrast, zopiclone 7.5 mg significantly increased mean SDLP as compared to placebo. Additionally, no drives were stopped before completion because of drowsiness after use of lemborexant or placebo, whereas three out of 96 total drives (3.1%) after use of zopiclone were stopped early. All participants completed all treatments. Across all conditions, all adverse events were of mild to moderate severity. The most commonly reported adverse events for lemborexant across doses included somnolence, headache, and dry mouth.
The Phase 1 study was designed to understand the impact of lemborexant on individuals’ next-morning driving ability. The study protocol followed the FDA’s guidance regarding inclusion of a positive control and placebo groups, elderly subjects, initial and steady state exposures for drugs with long half-lives, and crossover design.
“Our aspiration is to address unmet needs for patients suffering from insomnia so that they can fall asleep, stay asleep and wake without impairment,” says Lynn Kramer, MD, chief clinical officer and chief medical officer, Neurology Business Group, Eisai, in a release. “Results from our Phase 1 safety study suggest no significant driving impairment with lemborexant, bolstering our confidence in this investigational agent being studied for the treatment of insomnia.”
John Renger, PhD, vice president, head of research & development and regulatory affairs, Purdue Pharma, says, “The on-road driving test, which is performed in a limited number of locations worldwide, includes supervising study participants while they drive on open roads, instead of a driving simulator, providing important insights to a medication’s impact on driving ability in real-world conditions. These data, along with outcomes from two robust Phase 3 studies, add to the growing body of scientific support for lemborexant and its potential utility in insomnia.”
On Day 2 and Day 9, the difference in least squares (LS) mean SDLP was below 1.0 cm, compared to placebo, and not significant. The upper bound of the 95% confidence intervals (CIs) for the LS mean changes in SDLP were all below 2.4 cm for all three doses of lemborexant on Days 2 and 9, indicating there was not clinically meaningful driving impairment. The upper bound of the 95% CIs for the mean changes in SDLP for zopiclone was greater than 2.4 cm on Days 2 and 9, demonstrating assay sensitivity.
Lemborexant is being jointly developed by Eisai and Purdue Pharma for the treatment of multiple sleep-wake disorders, including insomnia disorder
This news brief discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.