Clinical trial NCT03471871: Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Healthy Subjects and Adult and Elderly Subjects With Mild Obstructive Sleep Apnea
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obstructive Sleep Apnea
Healthy Subjects
Keywords: Elderly Healthy Subjects
Adult Healthy Subjects
Lemborexant
Respiratory Safety
Peripheral Oxygen Saturation
Total Sleep Time
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Purdue Pharma LP
First posted: 2018-03-21
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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

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.

Primary outcomes:
measure: HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment
timeFrame: Day 1
measure: OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment
timeFrame: Day 8
Secondary outcomes:
measure: HV Cohort: AHI on Day 1 of Treatment
timeFrame: Day 1
measure: OSA Cohort: AHI on Day 1 of Treatment
timeFrame: Day 1
measure: HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment
timeFrame: Day 1
measure: 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
timeFrame: Day 1
measure: OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment
timeFrame: Day 1 and Day 8
measure: OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment
timeFrame: Day 1 and Day 8
measure: 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
timeFrame: Day 1 and Day 8
Other outcomes:
Locations:
city: Glendale
country: United States
facility: PACT
state: Arizona
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: San Diego
country: United States
facility: Pacific Research Network. LLC
state: California
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Atlanta
country: United States
facility: Neurotrials Research, Inc
state: Georgia
city: Chevy Chase
country: United States
facility: The Center for Sleep & Wake Disorders
state: Maryland
city: Columbia
country: United States
facility: Advarra
state: Maryland
city: New York
country: United States
facility: Clinilabs Drug Development
state: New York
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
Study officials:
References: