A Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Participants With Moderate to Severe Obstructive Sleep Apnea, and in Adult and Elderly Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease

NCT04647383 | Completed Phase 1 Results FDA Drug

• 1 other identifier: E2006-A001-113
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 11

Brief Summary

The primary purpose of the study is to determine whether lemborexant increases the apnea hypopnea index (AHI) on Day 8 of treatment in adult and elderly participants (adults greater than or equal to \[\>=\] 45 to less than \[\<\] 65 years; elderly \>=65 to 90 years) with moderate to severe obstructive sleep apnea (OSA) compared with placebo, and using pulse oximetry determine whether lemborexant decreases the peripheral oxygen saturation (SpO2) during total sleep time (TST) on Day 8 of treatment in adult and elderly participants (adults \>=45 to \<65 years; elderly \>=65 to 90 years) with moderate to severe chronic obstructive pulmonary disease (COPD) compared with placebo.

Conditions

Sleep Apnea, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiration Disorders

Keywords

E2006; Lemborexant; Peripheral Oxygen Saturation; Apnea Hypopnea Index

Outcome Measures

Primary Outcomes (2)

• OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment Periods 1 and 2

  AHI was the number of apneas and hypopneas divided by the total sleep time (TST) (in minutes) and multiplied by 60 (minute per hour \[min/hour\]) (that is, the average number of apneas and hypopneas per hour of sleep), as defined by the American Academy of Sleep Medicine. An AHI greater than or equal to (\>=) 5 to less than (\<) 15 is classed as mild, AHI \>=15 to \<30 as moderate, and AHI \>=30 as severe. TST was defined as the total time asleep in minutes using polysomnography (PSG).

  Day 8 of Treatment Periods 1 and 2 (up to Day 30)

• COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2

  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 PSG.

  Day 8 of Treatment Periods 1 and 2 (up to Day 30)

Secondary Outcomes (10)

• OSA Cohort: AHI on Day 1 of Treatment Periods 1 and 2

  Day 1 of Treatment Periods 1 and 2 (up to Day 23)

• OSA Cohort: Peripheral SpO2 During TST on Days 1 and 8 of Treatment Periods 1 and 2

  Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)

• OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2

  Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)

• OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2

  Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)

• OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2

  Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)

Study Arms (4)

OSA Cohort, Sequence A: Placebo + Lemborexant 10 mg

EXPERIMENTAL

Participants with 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 will be maintained between the 2 treatment periods.

Drug: Placebo; Drug: Lemborexant 10 mg

OSA Cohort, Sequence B: Lemborexant 10 mg + Placebo

EXPERIMENTAL

Participants with 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 will be maintained between the 2 treatment periods.

Drug: Placebo; Drug: Lemborexant 10 mg

COPD Cohort, Sequence C: Placebo + Lemborexant 10 mg

EXPERIMENTAL

Participants with COPD 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 will be maintained between the 2 treatment periods.

Drug: Placebo; Drug: Lemborexant 10 mg

COPD Cohort, Sequence D: Lemborexant 10 mg + Placebo

EXPERIMENTAL

Participants with COPD 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 will be maintained between the 2 treatment periods.

Drug: Placebo; Drug: Lemborexant 10 mg

Interventions

Placebo DRUG

OSA: Lemborexant-matched oral placebo will be administered at bedtime in the clinic (within 5 minutes before lights off) or at home when not in the clinic.

Also known as: E2006

OSA Cohort, Sequence A: Placebo + Lemborexant 10 mg; OSA Cohort, Sequence B: Lemborexant 10 mg + Placebo

Lemborexant 10 mg DRUG

OSA: 10 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes before lights off) or at home when not in the clinic.

Also known as: E2006

OSA Cohort, Sequence A: Placebo + Lemborexant 10 mg; OSA Cohort, Sequence B: Lemborexant 10 mg + Placebo

Eligibility Criteria

• Age: 45 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age \>=45 and \<=90 at the time of informed consent
• Voluntary agreement and ability to provide written informed consent
• Body mass index (BMI) \<40 Kilogram per meter square (kg/m\^2)
• Reports habitually sleeping for at least 5.5 hours per night
• Reports habitual bedtime between 21:00 and midnight
• Agrees to stay in bed for 7 hours per night for the duration of the study
• At Screening Visit 2: Has completed the sleep diary for at least 5 consecutive nights
• At Screening Visit 2: Confirmation of mean habitual bedtime (MHB) between 21:00 and midnight (sleep diary)
• Moderate to severe OSA diagnosed according to the criteria of the ICSD, confirmed by PSG (home sleep testing by portable monitor is acceptable) within the previous 5 years or a repeated PSG during screening
• On screening PSG: moderate OSA (defined as 15 \<=AHI \<30) or severe OSA (defined as AHI \>=30 per hour)
• SpO2 \>=94% assessed as part of vital signs at Screening Visit 1
• Screening spirometry performed as per the Global Initiative for Obstructive Lung Disease (GOLD) recommendations
• On screening spirometry, based on post-bronchodilator Forced Expiratory Volume in 1 second (FEV1):
• FEV1/Forced Vital Capacity (FVC) \<0.70 and one of the following:
• % \<=FEV1 \<80% predicted (GOLD 2 Classification for moderate COPD) or

You may not qualify if:

• Females of childbearing potential
• 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 symptoms of rapid eye movement (REM) Behavior Disorder, sleep-related violent behavior, sleep-driving, or sleep-eating, or symptoms of another parasomnia that in the investigator's opinion make 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
• A prolonged QT interval by Fredericia (QTcF) (QTcF \>450 milliseconds \[ms\]) as demonstrated by a repeated electrocardiogram (ECG) at Screening
• Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale \[C-SSRS\])
• Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS) within 10 years of Screening
• Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
• Hypersensitivity to the study drug or any of the excipients
• Used any prohibited prescription or over-the-counter medications within 1 week or 5 half-lives, whichever is longer, before the screening PSG
• Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (11)

Pulmonary Associates

Glendale, Arizona, 85306, United States

Location

Pacific Research Network

San Diego, California, 92103, United States

Location

Teradan Clinical Trials

Brandon, Florida, 33511, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

Clinical Trials of Florida, LLC

Miami, Florida, 33186, United States

Location

Clinical Site Partners Orlando, LLC

Winter Park, Florida, 32789, United States

Location

NeuroTrials Research Inc.

Atlanta, Georgia, 30328, United States

Location

GNP Research

Valdosta, Georgia, 31605, United States

Location

CTI Clinical Trial & Consulting Services

Cincinnati, Ohio, 45212, United States

Location

Intrepid Research, LLC

Cincinnati, Ohio, 45245, United States

Location

Related Publications (3)

• 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

• Cheng JY, Lorch D, Hall N, Moline M. Respiratory safety of lemborexant in adult and elderly subjects with moderate-to-severe chronic obstructive pulmonary disease. J Sleep Res. 2025 Apr;34(2):e14334. doi: 10.1111/jsr.14334. Epub 2024 Sep 12.

  PMID: 39266012 DERIVED

• Cheng JY, Lorch D, Lowe AD, Uchimura N, Hall N, Shah D, Moline M. A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea. J Clin Sleep Med. 2024 Jan 1;20(1):57-65. doi: 10.5664/jcsm.10788.

  PMID: 37677076 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiration Disorders

Interventions

lemborexant

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2020
• First Posted: November 30, 2020
• Study Start: January 6, 2021
• Primary Completion: February 10, 2022
• Study Completion: February 10, 2022
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share

Locations

US (11)