Jun 11, 2019
WOODCLIFF LAKE, N.J., June 11, 2019 /PRNewswire/ -- Eisai Inc. today announced data on the respiratory safety of investigational lemborexant with multiple and single dosing in healthy adult and elderly individuals, as well as in those with mild obstructive sleep apnea (OSA). Lemborexant, an investigational agent for sleep-wake regulation, is currently being studied for the treatment of insomnia, a sleep-wake disorder, and irregular sleep-wake rhythm disorder (ISWRD). These studies were presented at the 33rd annual meeting of the Associated Professional Sleep Societies (SLEEP 2019) in San Antonio.
Insomnia is a chronic condition that leads to significant distress or impairment in daily functioning and often affects the ability of patients to wake ready the next day.1 Respiratory safety is an important consideration in the treatment of insomnia, particularly in vulnerable individuals, such as the elderly and those with OSA.2 Some currently available treatment options, including sedative-hypnotic medications, are associated with central respiratory depression.3
"Given the respiratory concerns regarding the treatment of insomnia and the vital importance of proper breathing during sleep, it is crucial that respiratory patterns are evaluated, particularly when caring for vulnerable populations," said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai.
Earlier this year, the U.S. Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for December 27, 2019.
Key respiratory safety data presented at SLEEP 2019 are from Study 102, a two-part study on the respiratory safety of lemborexant.
Respiratory Safety of Lemborexant in Adult and Elderly Subjects With Mild Obstructive Sleep Apnea (Poster 103/Abstract 0429)
This Phase 1, multicenter, multiple-dose, randomized, double-blind, placebo-controlled, two-period crossover study examined pharmacodynamic respiratory safety parameters in subjects with mild OSA following a single dose or multiple doses of lemborexant. Thirty-six adult and elderly subjects (aged 18 to 90 years; mean age=57.2) with mild OSA completed the study and were randomized to receive either lemborexant 10 mg or placebo for two treatment periods of eight nights each, separated by a washout period of at least 14 days. The study met its primary endpoint, finding there was no difference in least squares mean (LSM) apnea-hypopnea index (AHI) for lemborexant 10 mg compared to placebo (9.93 events per hour of sleep with lemborexant 10 mg and 10.00 with placebo) after multiple doses during total sleep time (TST).
The study also met all secondary endpoints, showing there was no difference in:
In addition, the following secondary endpoint was met, assessing if there was a difference in percentage of TST during which SpO2 dipped below the defined thresholds (less than 90%; less than 85%; less than 80%) after single (1.349% with lemborexant 10 mg and 1.037% with placebo; 0.170% and 0.102%; 0.014% and 0.012%) or multiple doses (1.102% with lemborexant 10 mg and 1.014% with placebo; 0.164% and 0.108%; 0.015% and 0.009%).
In these study populations, treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The incidence of TEAEs reported was 15.8% with lemborexant 10 mg and 13.2% with placebo. The most common reported TEAE was somnolence (5.3%) with lemborexant 10 mg.
Respiratory Safety of Lemborexant in Healthy Adult and Elderly Subjects (Poster 104/Abstract 0430)
This Phase 1, multicenter, single-dose, randomized, double-blind, placebo-controlled, three-period crossover study examined whether a single dose of lemborexant decreased SpO2 during TST in healthy adult and elderly subjects compared with placebo. Sixteen participants (aged 18 to 90 years; mean age=48.5 years) completed the study and were randomized into one of three treatment sequences to receive either placebo, lemborexant 10 mg, or lemborexant 25 mg, separated by a washout period of at least 14 days. The study met its primary endpoint, finding there was no difference in LSM SpO2 during TST with a single dose of lemborexant compared with placebo (94.99% with lemborexant 10 mg, 95.06% with lemborexant 25 mg, and 95.35% with placebo).
The study met secondary endpoints, evaluating the difference in LSM AHI during TST for either dose of lemborexant compared to placebo (5.05 events per hour of sleep with lemborexant 10 mg, 3.37 with lemborexant 25 mg and 4.53 with placebo). In addition, the study assessed the differences with either dose of lemborexant compared to placebo in the percentage of TST during which SpO2 dipped below 90% as measured by LSM (0.218% with lemborexant 10 mg, 0.277% with lemborexant 25 mg, and 0.033% with placebo), below 85% (0.004% with lemborexant 10 mg, 0.043% with lemborexant 25 mg, and -0.001% with placebo) or below 80% (0.002%, 0.001% and 0%).
TEAEs and treatment-related TEAEs were mild in severity. The incidence of TEAEs reported was 6.3% with lemborexant 10 mg, 23.5% with lemborexant 25 mg and 6.3% with placebo. The most common reported TEAE was somnolence, 6.3% with lemborexant 10 mg and 5.9% with lemborexant 25 mg. Lemborexant 10 mg is the maximum dose in Phase 3 clinical trials.
Information about completed and ongoing lemborexant clinical studies is available at clinicaltrials.gov.
This release 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 investigational agent will successfully complete clinical development or gain health authority approval.
<Notes to editors>
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SOURCE Eisai Inc.