Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Healthy Subjects and Adult and Elderly Subjects With Mild Obstructive Sleep Apnea

NCT03471871 | Completed Phase 1 Results FDA Drug

• 1 other identifier: E2006-A001-102
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 11

Brief Summary

This study will be conducted to determine whether lemborexant as compared to placebo decreases the peripheral oxygen saturation during total sleep time in healthy adult and elderly participants after a single dose of treatment and to determine whether it increases the apnea-hypopnea index after single and multiple doses of treatment in adult and elderly participants with mild obstructive sleep apnea (OSA).

Conditions

Obstructive Sleep Apnea; Healthy Subjects

Keywords

Elderly Healthy Subjects; Adult Healthy Subjects; Lemborexant; Respiratory Safety; Peripheral Oxygen Saturation; Total Sleep Time

Outcome Measures

Primary Outcomes (2)

• HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment

  SpO2 is an estimate of the amount of oxygen in the blood. It is the percentage of hemoglobin containing oxygen compared to the total amount of hemoglobin in the blood (that is, oxygenated hemoglobin versus oxygenated and non-oxygenated hemoglobin). SpO2 was monitored by noninvasive method known as transmissive pulse oximetry. TST was defined as the total time asleep in minutes using polysomnography (PSG).

  Day 1

• OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment

  The AHI is the number of apneas and hypopneas per hour of sleep. AHI less than 5 is considered normal. An AHI from 5 to 14 denotes mild sleep apnea, 15 to 30 is moderate, while a greater than 30 AHI is considered severe.

  Day 8

Secondary Outcomes (7)

• HV Cohort: AHI on Day 1 of Treatment

  Day 1

• OSA Cohort: AHI on Day 1 of Treatment

  Day 1

• HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment

  Day 1

• HV Cohort: Percentage of Participants With at Least One Incident of SpO2 <90% for at Least 30 Seconds During TST on Day 1 of Treatment

  Day 1

• OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment

  Day 1 and Day 8

Study Arms (5)

HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg

EXPERIMENTAL

Eligible healthy adult and elderly participants will receive lemborexant-matched placebo (3 matched tablets) on the night of Day 1 of Treatment Period 1, followed by lemborexant 10 mg (1 lemborexant 10 mg tablet and 2 matching placebo tablets) on the night of Day 1 of Treatment Period 2, and then lemborexant 25 mg (2 lemborexant 10 mg tablets and 1 lemborexant 5 mg tablet) on the night of Day 1 of Treatment Period 3. A washout period of 14 days was maintained between each Treatment Period.

Drug: Placebo; Drug: Lemborexant 10 mg; Drug: Lemborexant 25 mg

HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo

EXPERIMENTAL

Eligible healthy adult and elderly participants will receive lemborexant 10 mg (1 lemborexant 10 mg tablet and 2 matching placebo tablets) on the night of Day 1 of Treatment Period 1, followed by lemborexant 25 mg (2 lemborexant 10 mg tablets and 1 lemborexant 5 mg tablet) on the night of Day 1 of Treatment Period 2, and then lemborexant-matched placebo (3 matched tablets) on the night of Day 1 of Treatment Period 3. A washout period of 14 days was maintained between each Treatment Period.

Drug: Placebo; Drug: Lemborexant 10 mg; Drug: Lemborexant 25 mg

HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg

EXPERIMENTAL

Eligible healthy adult and elderly participants will receive lemborexant 25 mg (2 lemborexant 10 mg tablet and 1 lemborexant 5 mg tablet) on the night of Day 1 of Treatment Period 1, followed by lemborexant-matched placebo (3 matched tablets) on the night of Day 1 of Treatment Period 2, and then lemborexant 10 mg (1 lemborexant 10 mg tablet and 2 matching placebo tablets) on the night of Day 1 of Treatment Period 3. A washout period of 14 days was maintained between each Treatment Period.

Drug: Placebo; Drug: Lemborexant 10 mg; Drug: Lemborexant 25 mg

OSA Cohort, Sequence D: Placebo, Lemborexant 10mg

EXPERIMENTAL

Eligible adult and elderly participants with mild OSA will receive one lemborexant-matched placebo tablet on the night of Day 1 through Day 8 of Treatment Period 1, followed by one lemborexant 10 mg tablet on the night of Day 1 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between each Treatment Period.

Drug: Placebo; Drug: Lemborexant 10 mg

OSA Cohort, Sequence E: Lemborexant 10mg, Placebo

EXPERIMENTAL

Eligible adult and elderly participants with mild OSA will receive one lemborexant 10 mg tablet on the night of Day 1 through Day 8 of Treatment Period 1, followed by one lemborexant-matched placebo tablet on the night of Day 1 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between each Treatment Period.

Drug: Placebo; Drug: Lemborexant 10 mg

Interventions

Placebo DRUG

HV: Lemborexant-matched oral placebo will be administered at bedtime in the clinic (within 5 minutes of lights off).

HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg; HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo; HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg

Lemborexant 10 mg DRUG

HV: 10 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off).

HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg; HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo; HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg

Lemborexant 25 mg DRUG

HV: 25 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off).

HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg; HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo; HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be included in this study:
• Male or female, age ≥18 years and ≤90 years at the time of informed consent
• Voluntary agreement and ability to provide written informed consent
• Reports habitually sleeping for at least 5.5 hours per night
• Agrees to stay in bed for 7 hours per night for the duration of treatment
• Reports habitual bedtime between 21:00 and 01:00
• Peripheral capillary oxygen saturation (SpO2) ≥94% assessed as part of vital signs at Screening Visit 1
• Body mass index (BMI) less than or equal to 32 kilograms per meters squared (kg/m\^2)
• On screening polysomnography (PSG) (Screening Visit 2): apnea-hypopnea index (AHI) \<5
• BMI ≤40 kg/m\^2
• OSA, diagnosed according to the criteria of the International Classification of Sleep Disorders, version 3
• On Screening PSG: AHI ≥5 to \<15 (mild severity)

You may not qualify if:

• A current diagnosis of restless legs syndrome, periodic limb movement disorder, circadian rhythm sleep disorder, or narcolepsy
• Reports symptoms potentially related to narcolepsy, that in the clinical opinion of the investigator indicate the need for referral for a diagnostic evaluation for the presence of narcolepsy
• A history of a parasomnia or parasomnia observed on the Screening PSG that in the investigator's opinion makes the participant unsuitable for the study
• Periodic Limb Movement with Arousal Index (PLMAI) as measured on the Screening PSG:
• Age 18 to \<65 years: PLMAI ≥10
• Age ≥65 years: PLMAI \>15
• History of or suspected drug or alcohol use disorder within approximately 2 previous years
• A positive urine drug test or breath alcohol test at Screening or Baseline, or unwilling to refrain from use of recreational drugs during the study
• Known to be human immunodeficiency virus positive
• Active viral hepatitis (B or C) as demonstrated by positive viral serology at Screening
• A prolonged QT/corrected QT (QTc) interval (QT interval corrected for heart rate using Fridericia's formula \[QTcF\] \>450 milliseconds \[ms\]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated if initial ECG indicates a QTcF interval \>450 ms)
• Comorbid nocturia resulting in the need to get out of bed to use the bathroom more than 3 times during the night
• Any history of medical or psychiatric condition that in the opinion of the investigator could affect the participant's safety or interfere with the study assessments
• Any suicidal ideation with intent to act with or without a plan, current or within 6 months before the Columbia - Suicide Severity Rating Scale (C-SSRS) administration during the Screening (e.g., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS
• Any suicidal behavior (per the Suicidal Behavior section of the C-SSRS) within 10 years of Screening

Sponsors & Collaborators

• Eisai Inc.: lead
• Purdue Pharma LP: collaborator

Study Sites (11)

PACT

Glendale, Arizona, 85306, United States

Location

Pulmonary Associates, PA

Phoenix, Arizona, 85006, United States

Location

Pacific Research Network. LLC

San Diego, California, 92103, United States

Location

PAB Clinical Research

Brandon, Florida, 33511, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

Neurotrials Research, Inc

Atlanta, Georgia, 30342, United States

Location

The Center for Sleep & Wake Disorders

Chevy Chase, Maryland, 20815, United States

Location

Advarra

Columbia, Maryland, 21046, United States

Location

Clinilabs Drug Development

New York, New York, 10019, United States

Location

CTI Clinical Research Center

Cincinnati, Ohio, 45212, United States

Location

Community Research

Cincinnati, Ohio, 45227, United States

Location

Related Publications (1)

• Khullar A, Boulos MI, Mak MSB, Moline M, Cheng JY, Hall N. Effect of lemborexant on sleep parameters and architecture in adult and elderly participants with mild-to-severe obstructive sleep apnea. Sleep Med. 2025 Oct;134:106757. doi: 10.1016/j.sleep.2025.106757. Epub 2025 Aug 18.

  PMID: 40848323 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

lemborexant

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 21, 2018
• Study Start: February 21, 2018
• Primary Completion: August 3, 2018
• Study Completion: August 3, 2018
• Last Updated: February 17, 2020
• Results First Posted: January 18, 2020

Record last verified: 2018-07

Locations

US (11)