Effects of Lemborexant as a Treatment for Moderate-to-severe OSA Patients With Low Arousal Threshold

A Randomized, Double-blind, Placebo-Controlled Trial on the Effects of Lemborexant as a Treatment for Moderate-to-severe OSA Patients With Low Arousal Threshold

The goal of this randomized, placebo-controlled, double-blind, crossover trial (1-week wash out period) is to compare 1 night of 5 mg Lemborexant to placebo administered before sleep in 10 moderate to severe OSA patients with low arousal threshold

The main questions it aims to answer are:

1. The effect of Lemborexant on apnea/hypopnea index (AHI) in moderate-to-severe OSA patients with low arousal threshold.

2. The effect of Lemborexant on the following parameters in moderate-to-severe OSA patients with low arousal threshold.

   • Arousal threshold
   • Mean and nadir oxygen saturation
   • Sleep latency
   • Sleep efficiency
   • Wake after sleep onset (WASO)
   • Percentage of time spent in NREM stage 1-3 and REM stage
   • Stanford Sleepiness Scale Questionnaire in the morning
   • The Oxford Sleep Resistance Test (OSLER) test

Participants will

• complete two overnight in-laboratory polysomnography (1-week washout)
• complete the OSLER test in the morning of the two overnight test

Researchers will compare with the placebo group to see if there is a difference in AHI

Research Design A randomized, placebo-controlled, double-blind, crossover trial (1-week wash out period) comparing 1 night of 5 mg Lemborexant to placebo administered before sleep.

Research Methodology Participants A total of 10 moderate to severe OSA patients with low arousal threshold are randomized 1:1 to either Lemborexant or placebo. The participants will complete two overnight in-laboratory polysomnography (1-week washout). Next-morning alertness will also be assessed using OSLER test, respectively.

Inclusion criteria

Eligible, healthy individuals with all the followings:

• Untreated OSA patient 18 - 65 years of age
• AHI ≥15 events/h of sleep
• Low arousal threshold

Study protocol All patients who were previously diagnosed with moderate to severe obstructive sleep apnea from baseline polysomnography with a low arousal threshold will be enrolled.

The patients will be subsequently randomized 1:1 to one of the two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period. Patients will receive either Lemborexant 5 mg per day or placebo prior 5 minutes before lights-out.

During this 2-night polysomnography, sleep parameters will be analyzed including AHI, mean and nadir oxygen indices, sleep latency, sleep efficiency, wake after sleep onset (WASO), and percentage of time spent in NREM, stage 1-3 and REM stage. The OSLER test to define vigilance will be obtained on the following morning.

Inclusion Criteria:

• Untreated OSA patient 18 - 65 years of age(49)
• AHI ≥15 events/h of sleep (moderate to severe)(23, 49)
• Low arousal threshold was defined using previously recommended criteria which allocated a score of 1 to each criterion that was satisfied: (apnea-hypopnea index, <30 events per hour) + (nadir oxygen saturation as measured by pulse oximetry >82.5%) + (fraction of hypopneas >58.3%). A score of 2 or above defined a low arousal threshold(50) (low arousal threshold defined as esophageal pressure values are 0 to -15 cmH2O)(27)

Exclusion Criteria:

• Previous allergy or adverse effects with Lemborexant or other sedatives - Taking any medication that affects sleep or other variable measured in this study - Pregnant or nursing mothers - Respiratory disorders other than OSA - Comorbid disease of poor controlled or resistant hypertension, uncontrolled cardiovascular or cerebrovascular disease
• Using CPAP or other dental devices
• Unable to tolerate equipment in this study