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

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).

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Other
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: August 3, 2018

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 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.

Interventions

  • Drug: Placebo
    • HV: Lemborexant-matched oral placebo will be administered at bedtime in the clinic (within 5 minutes of lights off).
  • Drug: Lemborexant 10 mg
    • HV: 10 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off).
  • Drug: Lemborexant 25 mg
    • HV: 25 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off).
  • Drug: Placebo
    • OSA: Lemborexant-matched oral placebo will be administered at bedtime in the clinic (within 5 minutes of lights off) in the evening of Days 1 and 8. On Days 2 to 7, participants will take study drug at home, immediately (within 5 minutes) of the time they intend to try to sleep.
  • Drug: Lemborexant 10 mg
    • OSA: 10 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off) in the evening of Days 1 and 8. On Days 2 to 7, participants will take study drug at home, immediately (within 5 minutes) of the time they intend to try to sleep.

Arms, Groups and Cohorts

  • Experimental: 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.
  • Experimental: 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
  • Experimental: 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.
  • Experimental: OSA Cohort, Sequence D: Placebo, Lemborexant 10mg
    • Eligible adult and elderly participants with mild OSA will receive lemborexant-matched placebo (3 matched tablets) on the night of Day 1 through Day 8 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 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between each Treatment Period.
  • Experimental: OSA Cohort, Sequence E: Lemborexant 10mg, Placebo
    • Eligible adult and elderly participants with mild OSA will receive lemborexant 10 mg (1 lemborexant 10 mg tablet and 2 matching placebo tablets) on the night of Day 1 through Day 8 of Treatment Period 1, followed by lemborexant-matched placebo (3 matched tablets) 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.

Clinical Trial Outcome Measures

Primary Measures

  • Healthy Volunteer (HV) Cohort: Mean Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment
    • Time Frame: Day 1
  • Obstructive Sleep Apnea (OSA) Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment
    • Time Frame: Day 8
    • AHI is the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (minutes per hour) (ie, the average number of apneas and hypopneas per hour of sleep), as defined by the American Academy of Sleep Medicine.

Secondary Measures

  • HV Cohort and OSA Cohort: AHI on Day 1 of Treatment
    • Time Frame: Day 1
    • AHI is the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (minutes per hour) (ie, the average number of apneas and hypopneas per hour of sleep), as defined by the American Academy of Sleep Medicine.
  • HV Cohort: Percentage of TST During which SpO2 is less than (<) 90% on Day 1 of Treatment
    • Time Frame: Day 1
  • HV Cohort: Percentage of TST During which SpO2 is <85% on Day 1 of Treatment
    • Time Frame: Day 1
  • HV Cohort: Percentage of TST During which SpO2 is <80% on Day 1 of Treatment
    • Time Frame: 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
    • Time Frame: Day 1
  • OSA Cohort: Mean SpO2 During TST on Day 1 and Day 8 of Treatment
    • Time Frame: Day 1 and Day 8
  • OSA Cohort: Percentage of TST During which the SpO2 is <90% on Day 1 and Day 8 of Treatment
    • Time Frame: Day 1 and Day 8
  • OSA Cohort: Percentage of TST During which the SpO2 is <85% on Day 1 and Day 8 of Treatment
    • Time Frame: Day 1 and Day 8
  • OSA Cohort: Percentage of TST During which the SpO2 is <80% on Day 1 and Day 8 of Treatment
    • Time Frame: 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
    • Time Frame: Day 1 and Day 8

Participating in This Clinical Trial

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

Additional Inclusion Criteria (Obstructive Sleep Apnea [OSA] Cohort):

  • BMI ≤40 kg/m^2
  • OSA, diagnosed according to the criteria of the International Classification of Sleep Disorders, version 3
  • On Screening PSG: AHI ≥5 to <15 (mild severity)

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:

1. Age 18 to <65 years: PLMAI ≥10

2. 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
  • A prolonged QT/corrected QT (QTc) interval (QT interval corrected for heart rate using Fridericia's formula [QTcF] >450 milliseconds [ms]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated if initial ECG indicates a QTcF interval >450 ms)
  • Comorbid nocturia resulting in the need to get out of bed to use the bathroom more than 3 times during the night
  • Any history of medical or psychiatric condition that in the opinion of the investigator could affect the participant's safety or interfere with the study assessments
  • Any suicidal ideation with intent to act with or without a plan, current or within 6 months before the Columbia – Suicide Severity Rating Scale (C-SSRS) administration during the Screening (e.g., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS
  • Any suicidal behavior (per the Suicidal Behavior section of the C-SSRS) within 10 years of Screening
  • Scheduled for surgery during the study that requires general anesthesia or administration of prohibited medications
  • Used any prohibited prescription or over-the-counter medications within 1 week or 5 half-lives, whichever is longer, before the Screening PSG
  • Hypersensitivity to lemborexant or excipients
  • Currently enrolled in another interventional clinical trial or used any investigational drug or device within 30 days or 5 times the half-life, whichever is longer preceding informed consent
  • Previously participated in other clinical trial of lemborexant
  • Is unable to avoid working a night shift within 2 weeks before the Screening PSG, or between the Screening PSG and End-of-Study
  • Has travelled across 3 or more time zones in the week prior to Screening, or plans to travel across more than 3 time zones during the study
  • Clinically significant findings based on vital signs, physical examination, ECG, or clinical laboratory tests

Additional Exclusion Criteria (HV Cohort):

  • Any valid event of SpO2 <90% during the Screening PSG
  • Current evidence of a clinically significant, active respiratory disorder. This includes bronchiectasis, emphysema, asthma, chronic obstructive pulmonary disease, 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
  • Presence of significant illness (including insomnia) that requires treatment or may influence the study assessments (e.g., 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 interfere with the study assessments. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded

Additional Exclusion Criteria (OSA Cohort):

  • SpO2 less than 80% for ≥ 5% of total sleep time during the Screening PSG
  • Uses or plans to use of continuous positive airway pressure device or dental appliance within 2 weeks of the Screening PSG (Screening Visit 2) or during the study
  • Current evidence of a clinically significant, active respiratory disorder other than OSA. This includes bronchiectasis, emphysema, asthma, chronic obstructive pulmonary disease 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
  • Current evidence of other clinically significant disease (e.g., 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. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded. Participants with insomnia disorder, who complain of difficulties with sleep onset and/or sleep maintenance, are eligible provided that they meet this criterion. Note that medications to treat insomnia are prohibited.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Eisai Inc.
  • Collaborator
    • Purdue Pharma LP
  • Provider of Information About this Clinical Study
    • Sponsor

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