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The investigational drug is well tolerated and does not increase patients’ auditory awakening threshold.
BALTIMORE—Lemborexant, an investigational treatment for insomnia, does not impair postural stability or driving ability on the morning after dosing, according to the results of phase I studies presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, lemborexant does not impair the ability to be awakened at night and helps patients return to sleep faster than placebo. Lemborexant is a dual orexin receptor antagonist in development for the treatment of insomnia and irregular sleep–wake rhythm disorder.
Comparing Lemborexant With Zolpidem
In one double-blind study, Patricia Murphy, PhD, Director of Clinical Research at Eisai, and colleagues randomized 63 healthy volunteers to one of four treatment sequences. The treatments were 5 mg of lemborexant, 10 mg of lemborexant, 6.25 mg of zolpidem, and placebo. Treatments were administered five minutes before bedtime.
At about four hours after bedtime, participants were exposed through earbuds to a 15-dB tone that became 5 dB louder every 15 seconds. Investigators recorded the volume required to awaken the participants. Within five minutes of awakening, participants had their postural stability measured by ataxiameter. After this assessment, the investigators used polysomnography to measure the time it took for participants to fall asleep again. Finally, participants underwent a second postural stability measurement after awakening in the morning. Participants entered a washout period of at least 14 days after each treatment and repeated the same tests for each treatment.
Approximately 78% of the population was female, and the average age was 63.6. Neither lemborexant nor zolpidem significantly increased participants’ auditory awakening threshold (AAT), compared with placebo. The mean AAT was 50 dB for placebo, 51.8 dB for 5 mg of lemborexant, 51.7 dB for 10 mg of lemborexant, and 58.4 dB for zolpidem.
The 5-mg dose of lemborexant did not significantly decrease postural stability, compared with placebo, when participants were awakened at night. The 10-mg dose of lemborexant caused a clinically meaningful decrease in postural stability, and zolpidem was associated with a decrease in stability that was twice that seen with 10 mg of lemborexant.
The mean latency to return to sleep was 40.9 minutes for placebo, 18.1 minutes for 5 mg of lemborexant, 12.1 minutes for 10 mg of lemborexant, and 19.6 minutes for zolpidem. Neither dose of lemborexant significantly affected postural stability after eight hours of sleep. Zolpidem was associated with a significant decrease in postural stability, compared with placebo, but the increase was not clinically meaningful.
Comparing Lemborexant With Zopiclone
In a separate study, Annemiek Vermeeren, PhD, Assistant Professor of Neuropsychology and Psychopharmacology at Maastricht University in the Netherlands, and colleagues evaluated whether lemborexant affected driving performance on the morning after dosing. They enrolled 48 healthy adults into the double-blind, incomplete crossover trial. Participants were randomized to one of 12 treatment sequences, and treatments included lemborexant (2.5 mg, 5 mg, or 10 mg) for eight consecutive days, zopiclone (7.5 mg) on Days 1 and 8 (with placebo on intervening days), and placebo for eight consecutive days. A washout period of at least 14 days followed each eight-day treatment period. Each participant received two of the three lemborexant doses.
Participants completed a practice driving test during screening, and driving performance was assessed at approximately nine hours after dosing on Days 2 and 9. Subjects were instructed to drive at 95 km/h within one lane for approximately one hour, while instruments on the vehicle measured their standard deviation of lateral position (SDLP).
The population’s mean age was 58.5, and 54.2% of participants were male. The mean increases from placebo in SDLP were less than 0.75 cm on both test days after all doses of lemborexant. These changes were neither statistically significant nor clinically meaningful. Zopiclone was associated with increases in SDLP of 2.04 cm on Day 2 and 1.88 cm on Day 9. These changes were statistically significant and clinically meaningful on both days.
The investigators categorized patients as between ages 21 and 65 or age 65 or older. The effects of lemborexant did not differ between adults older and younger than 65 or between males and females.
The driving instructor terminated three of 384 driving tests early. All participants whose tests were terminated had taken zopiclone.
The investigators did not observe any serious adverse events, severe treatment-emergent adverse events, or treatment-emergent adverse events leading to study discontinuation. The most common treatment-emergent adverse events reported after treatment with lemborexant were somnolence, headache, and dry mouth. The most common treatment-emergent adverse events reported after treatment with zopiclone were somnolence, dysgeusia, and dizziness.
Eisai and Purdue Pharma, the developers of lemborexant, funded the studies.
—Erik Greb
Suggested Reading
Murphy P, Moline M, Mayleben D, et al. Lemborexant, A dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299.
The investigational drug is well tolerated and does not increase patients’ auditory awakening threshold.
The investigational drug is well tolerated and does not increase patients’ auditory awakening threshold.
BALTIMORE—Lemborexant, an investigational treatment for insomnia, does not impair postural stability or driving ability on the morning after dosing, according to the results of phase I studies presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, lemborexant does not impair the ability to be awakened at night and helps patients return to sleep faster than placebo. Lemborexant is a dual orexin receptor antagonist in development for the treatment of insomnia and irregular sleep–wake rhythm disorder.
Comparing Lemborexant With Zolpidem
In one double-blind study, Patricia Murphy, PhD, Director of Clinical Research at Eisai, and colleagues randomized 63 healthy volunteers to one of four treatment sequences. The treatments were 5 mg of lemborexant, 10 mg of lemborexant, 6.25 mg of zolpidem, and placebo. Treatments were administered five minutes before bedtime.
At about four hours after bedtime, participants were exposed through earbuds to a 15-dB tone that became 5 dB louder every 15 seconds. Investigators recorded the volume required to awaken the participants. Within five minutes of awakening, participants had their postural stability measured by ataxiameter. After this assessment, the investigators used polysomnography to measure the time it took for participants to fall asleep again. Finally, participants underwent a second postural stability measurement after awakening in the morning. Participants entered a washout period of at least 14 days after each treatment and repeated the same tests for each treatment.
Approximately 78% of the population was female, and the average age was 63.6. Neither lemborexant nor zolpidem significantly increased participants’ auditory awakening threshold (AAT), compared with placebo. The mean AAT was 50 dB for placebo, 51.8 dB for 5 mg of lemborexant, 51.7 dB for 10 mg of lemborexant, and 58.4 dB for zolpidem.
The 5-mg dose of lemborexant did not significantly decrease postural stability, compared with placebo, when participants were awakened at night. The 10-mg dose of lemborexant caused a clinically meaningful decrease in postural stability, and zolpidem was associated with a decrease in stability that was twice that seen with 10 mg of lemborexant.
The mean latency to return to sleep was 40.9 minutes for placebo, 18.1 minutes for 5 mg of lemborexant, 12.1 minutes for 10 mg of lemborexant, and 19.6 minutes for zolpidem. Neither dose of lemborexant significantly affected postural stability after eight hours of sleep. Zolpidem was associated with a significant decrease in postural stability, compared with placebo, but the increase was not clinically meaningful.
Comparing Lemborexant With Zopiclone
In a separate study, Annemiek Vermeeren, PhD, Assistant Professor of Neuropsychology and Psychopharmacology at Maastricht University in the Netherlands, and colleagues evaluated whether lemborexant affected driving performance on the morning after dosing. They enrolled 48 healthy adults into the double-blind, incomplete crossover trial. Participants were randomized to one of 12 treatment sequences, and treatments included lemborexant (2.5 mg, 5 mg, or 10 mg) for eight consecutive days, zopiclone (7.5 mg) on Days 1 and 8 (with placebo on intervening days), and placebo for eight consecutive days. A washout period of at least 14 days followed each eight-day treatment period. Each participant received two of the three lemborexant doses.
Participants completed a practice driving test during screening, and driving performance was assessed at approximately nine hours after dosing on Days 2 and 9. Subjects were instructed to drive at 95 km/h within one lane for approximately one hour, while instruments on the vehicle measured their standard deviation of lateral position (SDLP).
The population’s mean age was 58.5, and 54.2% of participants were male. The mean increases from placebo in SDLP were less than 0.75 cm on both test days after all doses of lemborexant. These changes were neither statistically significant nor clinically meaningful. Zopiclone was associated with increases in SDLP of 2.04 cm on Day 2 and 1.88 cm on Day 9. These changes were statistically significant and clinically meaningful on both days.
The investigators categorized patients as between ages 21 and 65 or age 65 or older. The effects of lemborexant did not differ between adults older and younger than 65 or between males and females.
The driving instructor terminated three of 384 driving tests early. All participants whose tests were terminated had taken zopiclone.
The investigators did not observe any serious adverse events, severe treatment-emergent adverse events, or treatment-emergent adverse events leading to study discontinuation. The most common treatment-emergent adverse events reported after treatment with lemborexant were somnolence, headache, and dry mouth. The most common treatment-emergent adverse events reported after treatment with zopiclone were somnolence, dysgeusia, and dizziness.
Eisai and Purdue Pharma, the developers of lemborexant, funded the studies.
—Erik Greb
Suggested Reading
Murphy P, Moline M, Mayleben D, et al. Lemborexant, A dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299.
BALTIMORE—Lemborexant, an investigational treatment for insomnia, does not impair postural stability or driving ability on the morning after dosing, according to the results of phase I studies presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, lemborexant does not impair the ability to be awakened at night and helps patients return to sleep faster than placebo. Lemborexant is a dual orexin receptor antagonist in development for the treatment of insomnia and irregular sleep–wake rhythm disorder.
Comparing Lemborexant With Zolpidem
In one double-blind study, Patricia Murphy, PhD, Director of Clinical Research at Eisai, and colleagues randomized 63 healthy volunteers to one of four treatment sequences. The treatments were 5 mg of lemborexant, 10 mg of lemborexant, 6.25 mg of zolpidem, and placebo. Treatments were administered five minutes before bedtime.
At about four hours after bedtime, participants were exposed through earbuds to a 15-dB tone that became 5 dB louder every 15 seconds. Investigators recorded the volume required to awaken the participants. Within five minutes of awakening, participants had their postural stability measured by ataxiameter. After this assessment, the investigators used polysomnography to measure the time it took for participants to fall asleep again. Finally, participants underwent a second postural stability measurement after awakening in the morning. Participants entered a washout period of at least 14 days after each treatment and repeated the same tests for each treatment.
Approximately 78% of the population was female, and the average age was 63.6. Neither lemborexant nor zolpidem significantly increased participants’ auditory awakening threshold (AAT), compared with placebo. The mean AAT was 50 dB for placebo, 51.8 dB for 5 mg of lemborexant, 51.7 dB for 10 mg of lemborexant, and 58.4 dB for zolpidem.
The 5-mg dose of lemborexant did not significantly decrease postural stability, compared with placebo, when participants were awakened at night. The 10-mg dose of lemborexant caused a clinically meaningful decrease in postural stability, and zolpidem was associated with a decrease in stability that was twice that seen with 10 mg of lemborexant.
The mean latency to return to sleep was 40.9 minutes for placebo, 18.1 minutes for 5 mg of lemborexant, 12.1 minutes for 10 mg of lemborexant, and 19.6 minutes for zolpidem. Neither dose of lemborexant significantly affected postural stability after eight hours of sleep. Zolpidem was associated with a significant decrease in postural stability, compared with placebo, but the increase was not clinically meaningful.
Comparing Lemborexant With Zopiclone
In a separate study, Annemiek Vermeeren, PhD, Assistant Professor of Neuropsychology and Psychopharmacology at Maastricht University in the Netherlands, and colleagues evaluated whether lemborexant affected driving performance on the morning after dosing. They enrolled 48 healthy adults into the double-blind, incomplete crossover trial. Participants were randomized to one of 12 treatment sequences, and treatments included lemborexant (2.5 mg, 5 mg, or 10 mg) for eight consecutive days, zopiclone (7.5 mg) on Days 1 and 8 (with placebo on intervening days), and placebo for eight consecutive days. A washout period of at least 14 days followed each eight-day treatment period. Each participant received two of the three lemborexant doses.
Participants completed a practice driving test during screening, and driving performance was assessed at approximately nine hours after dosing on Days 2 and 9. Subjects were instructed to drive at 95 km/h within one lane for approximately one hour, while instruments on the vehicle measured their standard deviation of lateral position (SDLP).
The population’s mean age was 58.5, and 54.2% of participants were male. The mean increases from placebo in SDLP were less than 0.75 cm on both test days after all doses of lemborexant. These changes were neither statistically significant nor clinically meaningful. Zopiclone was associated with increases in SDLP of 2.04 cm on Day 2 and 1.88 cm on Day 9. These changes were statistically significant and clinically meaningful on both days.
The investigators categorized patients as between ages 21 and 65 or age 65 or older. The effects of lemborexant did not differ between adults older and younger than 65 or between males and females.
The driving instructor terminated three of 384 driving tests early. All participants whose tests were terminated had taken zopiclone.
The investigators did not observe any serious adverse events, severe treatment-emergent adverse events, or treatment-emergent adverse events leading to study discontinuation. The most common treatment-emergent adverse events reported after treatment with lemborexant were somnolence, headache, and dry mouth. The most common treatment-emergent adverse events reported after treatment with zopiclone were somnolence, dysgeusia, and dizziness.
Eisai and Purdue Pharma, the developers of lemborexant, funded the studies.
—Erik Greb
Suggested Reading
Murphy P, Moline M, Mayleben D, et al. Lemborexant, A dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299.