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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 2-Period, Crossover Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Subjects With Moderate to Severe Obstructive Sleep Apnea and Adult and Elderly Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04647383
• Other study ID #: E2006-A001-113
• Status: Completed
• Phase: Phase 1
• Start date: January 6, 2021
• Est. completion date: February 10, 2022

Study information

• Verified date: February 2022
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: February 10, 2022
• Est. primary completion date: February 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 90 Years

Eligibility

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) Additional Inclusion Criteria (OSA Cohort)

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 Additional Inclusion Criteria (COPD Cohort)

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 Additional Exclusion Criteria (OSA Cohort)

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 Additional Exclusion Criteria (COPD Cohort)

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.

Related Conditions & MeSH terms

• Apnea
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Respiration Disorders
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	NeuroTrials Research Inc.	Atlanta	Georgia
United States	Teradan Clinical Trials	Brandon	Florida
United States	CTI Clinical Trial & Consulting Services	Cincinnati	Ohio
United States	Intrepid Research, LLC	Cincinnati	Ohio
United States	St. Francis Medical Institute	Clearwater	Florida
United States	Pulmonary Associates	Glendale	Arizona
United States	Research Centers of America	Hollywood	Florida
United States	Clinical Trials of Florida, LLC	Miami	Florida
United States	Pacific Research Network	San Diego	California
United States	GNP Research	Valdosta	Georgia
United States	Clinical Site Partners Orlando, LLC	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	OSA Cohort: AHI on Day 1 of Treatment Periods 1 and 2	AHI was the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (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 >=5 to <15 is classed as mild, >=15 to <30 as moderate, and AHI >=30 as severe. TST was defined as the total time asleep in minutes using PSG.	Day 1 of Treatment Periods 1 and 2 (up to Day 23)
Secondary	OSA Cohort: Peripheral SpO2 During TST on Days 1 and 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.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2	TST was defined as the total time asleep in minutes using PSG. 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.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2	ODI was defined as (oxygen desaturations >=3%*60)/TST (that is, the average number of oxygen desaturations >=3% per hour of sleep), as defined by the American Academy of Sleep Medicine. TST was defined as the total time asleep in minutes using PSG.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2	Desaturation was defined as decrease in the mean SpO2 of >=3% (over the last 120 seconds) that lasts for at least 10 seconds. 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.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	COPD Cohort: Peripheral SpO2 During TST on Day 1 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 1 of Treatment Periods 1 and 2 (up to Day 23)
Secondary	COPD Cohort: AHI on Days 1 and 8 of Treatment Periods 1 and 2	AHI was the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (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 >=5 to <15 is classed as mild, >=15 to <30 as moderate, and AHI >=30 as severe. TST was defined as the total time asleep in minutes using PSG.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2	TST was defined as the total time asleep in minutes using PSG. 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.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	COPD Cohort: Mean ODI on Days 1 and 8 of Treatment Periods 1 and 2	ODI was defined as (oxygen desaturations >=3%*60)/TST (that is, the average number of oxygen desaturations >=3% per hour of sleep), as defined by the American Academy of Sleep Medicine. TST was defined as the total time asleep in minutes using PSG.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Secondary	COPD Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2	Desaturation was defined as decrease in the mean SpO2 of >=3% (over the last 120 seconds) that lasts for at least 10 seconds. 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.	Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)