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

NCT ID: NCT04647383

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-06
• Study Completion Date: 2022-02-10

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

OSA Cohort, Sequence A: Placebo + Lemborexant 10 mg

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Lemborexant 10 mg

Intervention Type: 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.

OSA Cohort, Sequence B: Lemborexant 10 mg + Placebo

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Lemborexant 10 mg

Intervention Type: 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.

COPD Cohort, Sequence C: Placebo + Lemborexant 10 mg

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

COPD: 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.

Lemborexant 10 mg

Intervention Type: DRUG

COPD: 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.

COPD Cohort, Sequence D: Lemborexant 10 mg + Placebo

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

COPD: 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.

Lemborexant 10 mg

Intervention Type: DRUG

COPD: 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.

Interventions

Placebo

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.

Intervention Type: DRUG

Lemborexant 10 mg

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.

Intervention Type: DRUG

Placebo

COPD: 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.

Intervention Type: DRUG

Lemborexant 10 mg

COPD: 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.

Intervention Type: DRUG

Other Intervention Names

E2006; E2006; E2006; E2006

Eligibility Criteria

Inclusion Criteria

1. Male or female, age >=45 and <=90 at the time of informed consent

2. Voluntary agreement and ability to provide written informed consent

3. Body mass index (BMI) <40 Kilogram per meter square (kg/m^2)

4. Reports habitually sleeping for at least 5.5 hours per night

5. Reports habitual bedtime between 21:00 and midnight

6. Agrees to stay in bed for 7 hours per night for the duration of the study

7. At Screening Visit 2: Has completed the sleep diary for at least 5 consecutive nights

8. At Screening Visit 2: Confirmation of mean habitual bedtime (MHB) between 21:00 and midnight (sleep diary)

9. 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

10. On screening PSG: moderate OSA (defined as 15 <=AHI <30) or severe OSA (defined as AHI >=30 per hour)

11. SpO2 >=94% assessed as part of vital signs at Screening Visit 1

12. Screening spirometry performed as per the Global Initiative for Obstructive Lung Disease (GOLD) recommendations

13. 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:
• 50% <=FEV1 <80% predicted (GOLD 2 Classification for moderate COPD) or
• 30% <=FEV1 <50% predicted (GOLD 3 Classification for severe COPD)

14. Moderate to severe COPD according to medical history and screening spirometry as per the GOLD criteria (GOLD 2019)

15. On screening PSG

• AHI <15
• SpO2 during wakefulness >90% (both supine and sitting)
• SpO2 during sleep >=80% for at least 75% of the recording period with no more than five continuous minutes <80% and with no SpO2 readings <70%

Exclusion Criteria

1. Females of childbearing potential

2. A current diagnosis of restless legs syndrome, periodic limb movement disorder, circadian rhythm sleep disorder, or narcolepsy

3. 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

4. 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

5. 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

6. A prolonged QT interval by Fredericia (QTcF) (QTcF >450 milliseconds [ms]) as demonstrated by a repeated electrocardiogram (ECG) at Screening

7. 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])

8. Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS) within 10 years of Screening

9. 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

10. Hypersensitivity to the study drug or any of the excipients

11. Used any prohibited prescription or over-the-counter medications within 1 week or 5 half-lives, whichever is longer, before the screening PSG

12. 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

13. Scheduled for surgery during the study that requires general anesthesia or administration of prohibited medications

14. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years

15. History of drug or alcohol dependency or abuse within approximately the last 2 years

16. Use of illegal recreational drugs (includes marijuana, regardless of whether prescribed for medicinal use)

17. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5*the half-life, whichever is longer preceding informed consent

18. Previously participated in other clinical trial of lemborexant

19. Exposure within the last 14 days to an individual with confirmed or probable corona virus disease 2019 (COVID-19) or symptoms within the last 14 days that are on the most recent Centers for Disease Control and Prevention (CDC) list of COVID symptoms or any other reason to consider the participant at potential risk for an acute COVID-19 infection

20. SpO2 <80% for >=5% of TST during the screening PSG

21. Use of a continuous positive airway pressure (CPAP) device or dental appliance within 2 weeks of the screening PSG, and does not agree to abstain from the use of a CPAP device or dental appliance from the

22. Current evidence of a clinically significant, active respiratory disorder other than OSA. This includes bronchiectasis, emphysema, asthma, COPD or any other pulmonary disorder identified by review of medical history, physical examination, and which in the opinion of the investigator, could compromise the participant's safety or interfere with study assessments

23. Current evidence of other clinically significant disease (example, psychiatric disorders, disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, cardiovascular system, or a congenital abnormality), malignancy within the past 5 years (other than adequately treated basal cell carcinoma or in situ carcinoma of the cervix), or chronic pain that in the opinion of the investigator could affect the participant's safety or interfere with the study assessments. Screening Visit through the last study visit

24. Use of continuous (>16 hours/day) oxygen therapy

25. Use of oxygen therapy during PSG

26. Determination that, in the opinion of the investigator, removal of oxygen therapy could affect the participant's safety or interfere with the study assessments

27. Recent changes to COPD medications or recent acute exacerbation of COPD (that is, needing hospitalization or treatment with oral corticosteroids and/or antibiotics) within 3 months of enrollment

28. On screening spirometry (COPD only):

• FEV1/FVC >=0.70
• FEV1 >=80% predicted (GOLD 1 Classification for mild COPD)
• FEV1 <30% predicted (GOLD 4 Classification for very severe COPD)

29. On screening PSG (COPD only):

• Moderate to severe OSA (AHI >=15)
• SpO2 <90% during wakefulness (supine and sitting)
• SpO2 during sleep <80% for 25% or more of the recording with >5 consecutive minutes <80% and any SpO2 reading <70%

30. ECG evidence of right ventricular hypertrophy or right heart failure

31. Screening hematocrit >55%

32. Use of a CPAP device or dental appliance within 2 weeks of the screening PSG, and does not agree to abstain from the use of a CPAP device or dental appliance from the Screening Visit through the last study visit

33. Current evidence of a clinically significant, active respiratory disorder other than COPD and mild OSA. This includes any other pulmonary disorder identified by review of medical history, physical examination, and which in the opinion of the investigator, could compromise the participant's safety or interfere with study assessments.

34. Current evidence of other clinically significant disease other than COPD and mild OSA (example, psychiatric disorders, disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, cardiovascular system, or a congenital abnormality), malignancy within the past 5 years (other than adequately treated basal cell carcinoma or in situ carcinoma of the cervix), or chronic pain that in the opinion of the investigator could affect the participant's safety or interfere with the study assessments.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pulmonary Associates

Glendale, Arizona, United States

Pacific Research Network

San Diego, California, United States

Teradan Clinical Trials

Brandon, Florida, United States

St. Francis Medical Institute

Clearwater, Florida, United States

Research Centers of America

Hollywood, Florida, United States

Clinical Trials of Florida, LLC

Miami, Florida, United States

Clinical Site Partners Orlando, LLC

Winter Park, Florida, United States

NeuroTrials Research Inc.

Atlanta, Georgia, United States

GNP Research

Valdosta, Georgia, United States

CTI Clinical Trial & Consulting Services

Cincinnati, Ohio, United States

Intrepid Research, LLC

Cincinnati, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40848323 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39266012 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37677076 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

E2006-A001-113

Identifier Type: -

Identifier Source: org_study_id