BALTIMORE — The circadian regulator tasimelteon (Hetlioz, Vanda Pharmaceuticals) demonstrated significant and clinically meaningful benefits in nighttime and daytime symptoms of jet lag disorder phase 3 results from a randomized, placebo-controlled trial show.
Tasimelteon improved total sleep time (TST) by 85 minutes vs placebo and also improved next-day alertness in this 8-hour phase advance clinical study, Christos Polymeropoulos, MD, medical director, Vanda Pharmaceuticals, reported here at SLEEP 2018: 32nd Annual Meeting of the Associated Professional Sleep Societies.
Tasimelteon is an MT1 and MT2 melatonin receptor agonist approved in the United States and Europe for adults with non–24-hour sleep-wake disorder (non-24), a rare chronic circadian rhythm disorder that affects almost exclusively people who are blind.
Jet lag disorder affects millions of travelers each year who cross multiple time zones. It is characterized by nighttime sleep disruption, a decrease in daytime alertness and impairment to social and occupational functioning. No treatment for jet lag disorder has been approved by the US Food and Drug Administration.
The JET8 study design induced the circadian challenge experienced by travelers who cross eight time zones (such as from the US West Coast to London, United Kingdom), which leads to jet lag disorder. A total of 318 healthy volunteers were admitted to a sleep unit and were subjected to a circadian challenge of an 8-hour advance to their usual bedtime. Participants took 20 mg tasimelteon or placebo 30 minutes before their 8-hour phase advance bedtime.
The prespecified primary endpoint was the TST in the first two thirds of the night (TST 2/3). Secondary endpoints included TST for the full night, latency to persistent sleep (LPS), and wake after sleep onset (WASO), as measured by polysomnography, as well as next-day alertness determined by the Karolinska Sleepiness Scale and the Visual Analog Scale.
Compared with placebo, tasimelteon led to significant improvement in TST 2/3, TST full night, LPS, and WASO.
Table. Summary of Primary and Secondary Endpoints
|Endpointa||Tasimelteon (min)||Placebo (min)||Difference||P Value|
|TST full night||315.8||230.3||85.5||<.0001|
|aAs assessed with polysomnography.|
Next-day alertness with tasimelteon also improved significantly. The average Karolinska Sleepiness Scale score (1 - 9) was 4.0 with tasimelteon vs 4.5 with placebo (P < .01), and the average Visual Analog Scale score (1 - 100) was 60.8 with tasimelteon vs 54.2 with placebo (P < .01).
The current findings build on the JET5 study that demonstrated similar benefits of tasimelteon in a circadian challenge of 5 hours advance of usual bedtime. Taken together, the results suggest that tasimelteon can be an effective therapeutic tool in the treatment of individuals who experience symptoms of jet lag disorder, the researchers say.
Reached for comment, Raman Malhotra, MD, American Academy of Sleep Medicine board member, said the JET8 data confirm the JET5 data "with a lot more patients and a little bit more delay, 8 hours."
"The gain of 85 minutes in total sleep time is pretty substantial and impressive and, as importantly, they seemed to function fine the next day, so daytime alertness did not seem to be compromised," said Malhotra, associate professor of neurology at the Washington University Sleep Center in St. Louis, Missouri.
He cautioned that "not every single person who travels eight time zones is going to need this. But there are some people who literally can't function in their job the morning after overseas travel who might benefit from this."
The study was supported by Vanda Pharmaceuticals Inc. All of the authors have financial relationships with the company. Malhotra has disclosed no relevant financial relationships.
SLEEP 2018: 32nd Annual Meeting of the Associated Professional Sleep Societies. Abstract LBA2. Presented June 4, 2018.
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Cite this: Circadian Regulator Effective for Jet Lag - Medscape - Jun 07, 2018.