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
Overview
- Phase
- Phase 1
- Intervention
- Lemborexant 10 mg
- Conditions
- Sleep Apnea, Obstructive
- Sponsor
- Eisai Inc.
- Enrollment
- 63
- Locations
- 11
- Primary Endpoint
- COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
- •Additional Inclusion Criteria (OSA Cohort)
- •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
Exclusion Criteria
- •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
- •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
Arms & Interventions
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.
Intervention: Lemborexant 10 mg
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.
Intervention: Placebo
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.
Intervention: Lemborexant 10 mg
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.
Intervention: Placebo
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.
Intervention: Placebo
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.
Intervention: Lemborexant 10 mg
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.
Intervention: Placebo
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.
Intervention: Lemborexant 10 mg
Outcomes
Primary Outcomes
COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2
Time Frame: Day 8 of Treatment Periods 1 and 2 (up to Day 30)
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.
OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment Periods 1 and 2
Time Frame: Day 8 of Treatment Periods 1 and 2 (up to Day 30)
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).
Secondary Outcomes
- 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: 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))
- COPD 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))
- COPD 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))
- 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))
- COPD Cohort: AHI 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))
- COPD Cohort: Peripheral SpO2 During TST on Day 1 of Treatment Periods 1 and 2(Day 1 of Treatment Periods 1 and 2 (up to Day 23))
- COPD Cohort: Mean 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))