A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Healthy Subjects and Adult and Elderly Subjects With Mild Obstructive Sleep Apnea
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Obstructive Sleep Apnea
- Sponsor
- Eisai Inc.
- Enrollment
- 146
- Locations
- 11
- Primary Endpoint
- HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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).
Detailed Description
Healthy Volunteer (HV) Cohort: The HV Cohort comprises a randomized, double-blind, placebo-controlled, 3-period crossover study. Eligible healthy adult and elderly participants will be randomized to treatment sequence A, B, or C, each consisting of 3 Treatment Periods, each of one night's duration, in which participants will receive a single dose of lemborexant 10 milligrams (mg), or lemborexant 25 mg, or placebo. Treatment Periods will be separated by a washout interval of at least 14 days. A sufficient number of participants will be randomized to ensure that 8 evaluable adult participants (\<65 years) and 4 evaluable elderly participants (≥65 years) complete the study. OSA Cohort: The OSA Cohort comprises a multiple-dose, randomized, double-blind, placebo-controlled, 2-period crossover study. Adult and elderly participants with mild OSA will be randomized to treatment sequence D or E, each consisting of 2 Treatment Periods, each of 8 nights' duration, in which participants will receive lemborexant 10 mg or placebo. The Treatment Periods will be separated by a washout interval of at least 14 days. A sufficient number of participants will be randomized to ensure that 20 evaluable adult participants (\<65 years) and 10 evaluable elderly participants (≥65 years) complete the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Additional Inclusion Criteria (Healthy Volunteer \[HV\] Cohort):
- •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
Exclusion Criteria
- •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
Arms & Interventions
OSA Cohort, Sequence E: Lemborexant 10mg, Placebo
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.
Intervention: Placebo
HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg
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.
Intervention: Placebo
HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg
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.
Intervention: Lemborexant 10 mg
HV Cohort,Sequence A:Placebo,Lemborexant 10mg,Lemborexant 25mg
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.
Intervention: Lemborexant 25 mg
HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo
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.
Intervention: Placebo
HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo
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.
Intervention: Lemborexant 10 mg
HV Cohort,Sequence B:Lemborexant 10mg,Lemborexant 25mg,Placebo
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.
Intervention: Lemborexant 25 mg
HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg
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.
Intervention: Placebo
HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg
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.
Intervention: Lemborexant 10 mg
HV Cohort,Sequence C:Lemborexant 25mg,Placebo,Lemborexant 10mg
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.
Intervention: Lemborexant 25 mg
OSA Cohort, Sequence D: Placebo, Lemborexant 10mg
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.
Intervention: Placebo
OSA Cohort, Sequence D: Placebo, Lemborexant 10mg
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.
Intervention: Lemborexant 10 mg
OSA Cohort, Sequence E: Lemborexant 10mg, Placebo
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.
Intervention: Lemborexant 10 mg
Outcomes
Primary Outcomes
HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment
Time Frame: Day 1
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).
OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment
Time Frame: Day 8
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.
Secondary Outcomes
- 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)
- OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment(Day 1 and Day 8)
- OSA Cohort: Percentage of Participants With at Least One Incident of SpO2 <90% for at Least 30 Seconds During TST on Day 1 and Day 8 of Treatment(Day 1 and Day 8)