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

Chulalongkorn University

Status and phase: Completed; Phase 2; Phase 1

Conditions: OSA

Treatments: Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1; Drug: Placebo Day 1; Drug: Placebo Day 2; Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2

Study type: Interventional

Funder types: Other

Identifiers

NCT05763329

218/64

Details and patient eligibility

About

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

Full description

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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10 participants in 2 patient groups, including a placebo group

Lemborexant

Experimental group

Description:

Patients will receive two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period The participants will receive Lemborexant 5 mg per day 5 minutes before lights-out for one dose for the first overnight sleep test of the experiment. After 1 week wash-out period, the participants will cross to the placebo arm and receive placebo 5 minutes before lights-out for one dose for the second overnight sleep test of the experiment.

Treatment:

Drug: Placebo Day 2

Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1

Placebo

Placebo Comparator group

Description:

Patients will receive two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period The participants will receive placebo 5 minutes before lights-out for one dose for the first overnight sleep test of the experiment. After 1 week wash-out period, the participants will cross to the Lemborexant arm and receive Lemborexant 5 mg per day 5 minutes before lights-out for one dose for the second overnight sleep test of the experiment.

Treatment:

Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2

Drug: Placebo Day 1