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

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

Study Overview

• Status: Completed
• Conditions: OSA
• Intervention / Treatment: Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1; Drug: Placebo Day 2; Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2; Drug: Placebo Day 1

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Pathum Wan, Bangkok, Thailand, 10330
      • Chulalongkorn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lemborexant; 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.	Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1; Patients will receive Lemborexant 5 mg per day on the first day of sleep test; Drug: Placebo Day 2; Patients will receive placebo on the second day of sleep test
Placebo Comparator: Placebo; 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.	Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2; Patients will receive Lemborexant 5 mg per day on the second day of sleep test; Drug: Placebo Day 1; Patients will receive placebo on the first day of sleep test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
apnea/hypopnea index (AHI)	AHI	through study completion, one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean and nadir oxygen saturation		through study completion, one week
Sleep latency (Time the patients fall asleep)	Time spent from light out to the first 20 consecutive 30-second period of nonwakefulness (minutes)	through study completion, one week
Sleep efficiency (Time the patients actually sleep through out the experiment)	Time the patient sleep per time in bed which is the total sleep time per time from light out until light on (total record time (TRT) (8 hours) (minutes)	through study completion, one week
Wake after sleep onset (WASO)	Total time of wakefulness after initial sleep onset until light on	through study completion, one week
Percentage of time spent in NREM stage 1-3 and REM stage		through study completion, one week
The Oxford Sleep Resistance Test (OSLER) test		through study completion, one week

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Principal Investigator: Sarocha Vivatvakin, MD, Department of Medicine, Faculty of Medicine, Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Polysomnography; Lemborexant; Obstructive Sleep Apnea (OSA); Apnea/Hypopnea Index (AHI); Low Arousal Threshold
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sleep Apnea, Obstructive; Apnea; Pharmaceutical Preparations; Dosage Forms; Tablets; lemborexant
• Other Study ID Numbers: 218/64

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No