The Optimal One-Month Dosing of Lemborexant for Moderate Obstructive Sleep Apnea (OSA) Patients With Low Arousal Threshold

Phase 2Not Yet RecruitingNCT07683442

Chulalongkorn University36 enrolled

Overview

The goal of this clinical trial is to investigate the 1-month treatment effects of different dose of lemborexant in moderate OSA adult patients (18-65 years of age) with low arousal threshold. The main questions it aims to answer are: Primary outcome measure: Apnea/hypopnea index (AHI) Secondary outcome measure: 1. Polysomnography parameters * Mean and nadir oxygen saturation * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency * Rapid eye movement (REM) latency * Percentage of time spent in Non-rapid eye movement (NREM) stage 1-3 and REM stage * Arousal index 2. Oxford Sleep Resistance Test (OSLER) test 3. Epworth Sleepiness Scale (ESS) 4. Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) 5. Pittsburgh Sleep Quality Index (PSQI) 6. Actigraphy parameters * Total sleep time * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency 7. Sleep diary parameters (Appendix 5) * Total sleep time * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency * Sleep quality Researchers will compare placebo to see if there is a difference in AHI. Participants will * participate a total of 3 phases of study (3-crossover trial) * each phrase the participants will receive either lemborexant 5 mg, lemborexant 10 mg, or placebo orally per day for 30 days with 2-week washout (depend on intervention arm whether the participants receive which intervention sequence) * complete three overnight in-laboratory polysomnography (2-week washout) at day 30 of each phrase * monitor actigraphy during day 1 to 29 of intervention of all periods * record sleep diary during day 1 to 29 of intervention of all periods * complete the OSLER test in the morning of the three overnight test * complete questionnaires including: Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T), Pittsburgh Sleep Quality Index (PSQI) at baseline (prior to intervention) and the night before overnight in-laboratory polysomnography

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Lemborexant 5 MG [Dayvigo] Period 1DRUG

Participants will receive lemborexant 5 mg per day for 30 days during first period

Placebo Period 1DRUG

Participants will receive placebo 5 mg per day for 30 days during the first period

Lemborexant 5 MG [Dayvigo] Period 2DRUG

Participant will receive lemborexant 5 mg per day for 30 days during the second period

Placebo Period 2DRUG

Participant will receive placebo 5 mg per day for 30 days during the second period

Lemborexant 5 MG [Dayvigo] Period 3DRUG

Participants will receive lemborexant 5 mg per day for 30 days during third period

Placebo Period 3DRUG

Participants will receive placebo per day for 30 days during third period

Lemborexant 10 MG [Dayvigo] Period 1DRUG

Participants will receive lemborexant 10 mg per day for 30 days during first period

Lemborexant 10 MG [Dayvigo] Period 2DRUG

Participants will receive lemborexant 10 mg per day for 30 days during second period

Lemborexant 10 MG [Dayvigo] Period 3DRUG

Participants will receive lemborexant 10 mg per day for 30 days during third period

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion criteria Individuals are eligible for participation in this study if they have all of the followings: 1. Patient, aged 18 - 65 years at the time of informed consent 2. Voluntary agreement and capable for giving written informed consent 3. Diagnosis with OSA according to the criteria of the International Classification of Sleep Disorders, version 3 Text Revision 4. Baseline screening polysomnography (PSG) demonstrated apnea-hypopnea index 15 - 30 events/h of sleep (moderate severity) 5. Patients identified as low arousal threshold using previously recommended criteria which allocated a score of 1 to each criterion: apnea-hypopnea index \< 30 events per hour, nadir oxygen saturation as measured by pulse oximetry \> 82.5%, and fraction of hypopneas \> 58.3%. A score of 2 or above defined a low arousal threshold. 6. Peripheral capillary oxygen saturation (SpO2) ≥ 94% measured during screening visit 7. Habitually sleeping ≥ 5.5 hours/night with usual bedtime falls within the range of 9:00 PM to 1:00 AM 8. Body mass index 18 - 40 kg/m2 Exclusion criteria Individuals were not eligible for participation in this study if they have any of the followings: 1. Previous allergy or adverse effects with Lemborexant or other sedatives 2. Pregnant or breastfeeding 3. Significant medical comorbidities that could affect individual safety and study assessment results, regarding investigators' opinion 4. Uncontrolled cardiovascular or cerebrovascular diseases 5. Neuromuscular diseases 6. Nasal anatomical defect 7. Significant psychiatric comorbidities that could affect individual safety and study assessment results, regarding investigators' opinion 8. Active respiratory disorders other than OSA 9. Central respiratory events (CAHI) \>25% of the total AHI 10. Diagnosis/symptoms of sleep-related disease other than OSA including narcolepsy, restless legs syndrome, periodic limb movement disorder, or circadian rhythm sleep-wake disorder 11. Severe hypersomnolence (ESS ≥16) 12. Peripheral capillary oxygen saturation (SpO2) \< 80% for ≥ 5% of total sleep time measured during screening visit 13. Driving-related sleepiness accident or near misses in the past 12 months 14. Safety-critical occupation 15. Using CPAP or other dental devices within 2 weeks of screening polysomnography until the end of the study 16. Unable to tolerate equipment in this study 17. Taking any medication that affects sleep or other variable measured in this study 18. Taking any medication with cytochrome P450 Family 3A (CYP3A) inhibitors and all CYP3A inducers 19. Drug or alcohol use disorder within 2 years before the study initiation or current excessive alcohol intake 20. Excessive caffeine intake

Outcomes

Primary Outcomes

Apnea/hypopnea index (AHI)

Apnea/hypopnea index (AHI) measured by polysomnography (scale: events/hour: minimum 0 event/hour - no maximum scoring; higher scores mean worse outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

Secondary Outcomes

Mean and nadir oxygen saturation

Mean and nadir oxygen saturation measured by polysomnography (scale: percent: minimum 0% - maximum 100%; higher scores mean better outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

Sleep efficiency

Sleep efficiency measured by polysomnography (scale: percent: minimum 0% - maximum 100%; higher scores mean better outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

Wake after sleep onset (WASO)

Wake after sleep onset (WASO) measured by polysomnography (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean worse outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

Sleep latency

Sleep latency measured by polysomnography (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean worse outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

REM latency

REM latency measured by polysomnography (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean worse outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

Percentage of time spent in NREM stage 1-3 and REM stage

Percentage of time spent in NREM stage 1-3 and REM stage measured by polysomnography (scale: percent: minimum 0% - maximum 100%; higher scores in NREM stage 3 and REM mean better outcome but higher scores in NREM stage 1 and 2 mean worse outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

Arousal index

Arousal index measured by polysomnography (scale: events/hour: minimum 0 event/hour - no maximum scoring; higher scores mean worse outcome)

Time frame: At day 30 during the overnight in-laboratory of each study period

OSLER error index

Oxford Sleep Resistance Test (OSLER) test (scale: events/hour: minimum 0 event/hour - no maximum scoring; higher scores mean worse outcome)

Time frame: On the morning of the in-laboratory polysomnography

Epworth Sleepiness Scale (ESS)

Epworth Sleepiness Scale (ESS) questionnaires (scale: point: minimum 0 point - maximum 24 point; higher scores mean worse outcome)

Time frame: Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period

Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T)

Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) (scale: point: minimum 5 point - maximum 20 point; higher scores mean better outcome)

Time frame: Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period

Pittsburgh Sleep Quality Index

Pittsburgh Sleep Quality Index (scale: point: minimum 0 point - maximum 21 point; higher scores mean worse outcome)

Time frame: Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period

Total sleep time

Total sleep time measured by actigraphy (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean better outcome)