Healthy Subjects, Obstructive Sleep Apnea
Conditions
Keywords
Elderly Healthy Subjects, Adult Healthy Subjects, Lemborexant, Respiratory Safety, Peripheral Oxygen Saturation, Total Sleep Time
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.
Interventions
DRUGPlacebo
HV: Lemborexant-matched oral placebo will be administered at bedtime in the clinic (within 5 minutes of lights off).
HV: 10 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off).
HV: 25 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes of lights off).
Sponsors
Purdue Pharma LP
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | Day 1 | 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. |
| 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 | 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. |
| HV Cohort: AHI on Day 1 of Treatment | Day 1 | 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. |
| 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 | 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. |
| 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 | 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: SpO2 During TST on Day 1 and Day 8 of Treatment | Day 1 and Day 8 | 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: AHI on Day 1 of Treatment | Day 1 | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 8 investigative sites in the United States from February 21, 2018 to August 3, 2018.
Pre-assignment details
In healthy volunteer (HV) cohort, 39 participants were screened and enrolled, of which 22 were screen failures, 17 were randomized to receive treatment. In obstructive sleep apnea (OSA) cohort, 107 participants were screened and enrolled, of which 68 were screen failures, 39 were randomized to receive treatment. Total participants enrolled=146
Participants by arm
| Arm | Count |
|---|---|
| HV Cohort Eligible healthy adult and elderly participants received lemborexant-matched placebo (3 placebo tablets), lemborexant 10 mg (1 lemborexant 10 mg tablet and 2 matching placebo tablets \[to maintain blind\]) or lemborexant 25 mg (2 lemborexant 10 mg tablets and 1 lemborexant 5 mg tablet), orally, once, in the evening (within 5 minutes of lights off) of Day 1 in the respective Treatment Period 1, 2 or 3. A washout period of 14 days was maintained between each treatment period. | 17 |
| OSA Cohort Eligible adult and elderly participants with mild OSA received one lemborexant-matched placebo or one lemborexant 10 mg, tablets, orally, once, in the evening (within 5 minutes of lights off) of Day 1 through Day 8 in the respective Treatment Period 1 or 2. A washout period of 14 days was maintained between each treatment period. | 39 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Follow Up (14 Days for Both HV and OSA) | Did Return to Clinic | 0 | 0 | 0 | 1 | 0 |
| Follow Up (14 Days for Both HV and OSA) | Protocol Deviation | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 1(HV:1 Day, OSA:8 Days) | Protocol deviation | 0 | 0 | 0 | 1 | 1 |
| Treatment Period 1(HV:1 Day, OSA:8 Days) | Work Demand: Return to work | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 2(HV:1 Day, OSA:8 Days) | Other | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | HV Cohort | OSA Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 13 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 26 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 16 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 23 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 35 Participants | 44 Participants |
| Sex: Female, Male Female | 12 Participants | 24 Participants | 36 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 17 | 0 / 38 | 0 / 38 |
| other Total, other adverse events | 1 / 16 | 1 / 16 | 4 / 17 | 5 / 38 | 6 / 38 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 17 | 0 / 38 | 0 / 38 |
Outcome results
Primary
HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment
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).
Time frame: Day 1
Population: Pharmacodynamic (PD) analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HV Cohort: Placebo | HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment | 95.34 percentage of oxygen saturation | Standard Deviation 0.9 |
| HV Cohort: Lemborexant 10 mg | HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment | 95.00 percentage of oxygen saturation | Standard Deviation 1.283 |
| HV Cohort: Lemborexant 25 mg | HV Cohort: Peripheral Oxygen Saturation (SpO2) During Total Sleep Time (TST) on Day 1 of Treatment | 95.07 percentage of oxygen saturation | Standard Deviation 1.311 |
p-value: 0.09995% CI: [-0.78, 0.07]Mixed effect model
p-value: 0.17695% CI: [-0.72, 0.14]Mixed effect model
Primary
OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment
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.
Time frame: Day 8
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HV Cohort: Placebo | OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment | 10.03 events (apnea plus hyponea) per hour | Standard Deviation 6.799 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment | 9.99 events (apnea plus hyponea) per hour | Standard Deviation 5.878 |
p-value: 0.94895% CI: [-1.95, 1.83]Mixed effect model
Secondary
HV Cohort: AHI on Day 1 of Treatment
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.
Time frame: Day 1
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HV Cohort: Placebo | HV Cohort: AHI on Day 1 of Treatment | 4.69 events (apnea plus hyponea) per hour | Standard Deviation 8.183 |
| HV Cohort: Lemborexant 10 mg | HV Cohort: AHI on Day 1 of Treatment | 5.29 events (apnea plus hyponea) per hour | Standard Deviation 10.484 |
| HV Cohort: Lemborexant 25 mg | HV Cohort: AHI on Day 1 of Treatment | 3.55 events (apnea plus hyponea) per hour | Standard Deviation 6.585 |
p-value: 0.63995% CI: [-1.72, 2.76]Mixed effect model
p-value: 0.29795% CI: [-3.4, 1.08]mixed effect model
Secondary
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
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.
Time frame: Day 1
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HV Cohort: Placebo | 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 | 31.3 percentage of participant |
| HV Cohort: Lemborexant 10 mg | 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 | 31.3 percentage of participant |
| HV Cohort: Lemborexant 25 mg | 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 | 37.5 percentage of participant |
Secondary
HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment
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.
Time frame: Day 1
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HV Cohort: Placebo | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <85% | 0 percentage of TST | Standard Deviation 0 |
| HV Cohort: Placebo | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <90% | 0.037 percentage of TST | Standard Deviation 0.0968 |
| HV Cohort: Placebo | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <80% | 0 percentage of TST | Standard Deviation 0 |
| HV Cohort: Lemborexant 10 mg | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <85% | 0.004 percentage of TST | Standard Deviation 0.0109 |
| HV Cohort: Lemborexant 10 mg | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <90% | 0.224 percentage of TST | Standard Deviation 0.3755 |
| HV Cohort: Lemborexant 10 mg | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <80% | 0.001 percentage of TST | Standard Deviation 0.0034 |
| HV Cohort: Lemborexant 25 mg | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <90% | 0.287 percentage of TST | Standard Deviation 0.5555 |
| HV Cohort: Lemborexant 25 mg | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <80% | 0.003 percentage of TST | Standard Deviation 0.0077 |
| HV Cohort: Lemborexant 25 mg | HV Cohort: Percentage of TST During Which SpO2 Was Less Than (<) 90 Percent (%), 85 % and 80 % on Day 1 of Treatment | SpO2 <85% | 0.047 percentage of TST | Standard Deviation 0.1516 |
Comparison: When SpO2 is \<90%p-value: 0.0395% CI: [0.025, 0.464]Mixed effect model
Comparison: SpO2 is \<85%p-value: 0.88595% CI: [-0.058, 0.067]Mixed effect model
Comparison: SpO2 is \<90%p-value: 0.09595% CI: [-0.034, 0.405]Mixed effect model
Comparison: SpO2 is \<85%p-value: 0.15895% CI: [-0.018, 0.107]Mixed effect model
Comparison: SpO2 is \<80%p-value: 0.46295% CI: [-0.002, 0.005]Mixed effect model
Comparison: SpO2 is \<80%p-value: 0.16695% CI: [-0.001, 0.006]Mixed effect model
Secondary
OSA Cohort: AHI on Day 1 of Treatment
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.
Time frame: Day 1
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HV Cohort: Placebo | OSA Cohort: AHI on Day 1 of Treatment | 10.24 events (apnea plus hyponea) per hour | Standard Deviation 7.094 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: AHI on Day 1 of Treatment | 10.29 events (apnea plus hyponea) per hour | Standard Deviation 6.681 |
p-value: 0.97995% CI: [-2.22, 2.17]Mixed effect model
Secondary
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
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.
Time frame: Day 1 and Day 8
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HV Cohort: Placebo | 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: SpO2 <90% | 67.6 percentage of participant |
| HV Cohort: Placebo | 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 8: SpO2 <90% | 75.7 percentage of participant |
| HV Cohort: Lemborexant 10 mg | 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: SpO2 <90% | 75.7 percentage of participant |
| HV Cohort: Lemborexant 10 mg | 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 8: SpO2 <90% | 83.8 percentage of participant |
Secondary
OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment
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.
Time frame: Day 1 and Day 8
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter. Here, 'number analyzed' signifies participants who were evaluable for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HV Cohort: Placebo | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 1: SpO2 <85% | 0.104 percentage of TST | Standard Deviation 0.3043 |
| HV Cohort: Placebo | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 8: SpO2 <90% | 1.011 percentage of TST | Standard Deviation 1.421 |
| HV Cohort: Placebo | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 1: SpO2 <90% | 1.044 percentage of TST | Standard Deviation 1.8851 |
| HV Cohort: Placebo | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 8: SpO2 <85% | 0.109 percentage of TST | Standard Deviation 0.2974 |
| HV Cohort: Placebo | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 1: SpO2 <80% | 0.012 percentage of TST | Standard Deviation 0.0483 |
| HV Cohort: Placebo | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 8: SpO2 <80% | 0.009 percentage of TST | Standard Deviation 0.0366 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 1: SpO2 <80% | 0.014 percentage of TST | Standard Deviation 0.0433 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 1: SpO2 <90% | 1.362 percentage of TST | Standard Deviation 2.617 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 1: SpO2 <85% | 0.170 percentage of TST | Standard Deviation 0.5132 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 8: SpO2 <80% | 0.015 percentage of TST | Standard Deviation 0.0603 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 8: SpO2 <90% | 1.102 percentage of TST | Standard Deviation 1.5469 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: Percentage of TST During Which the SpO2 is <90%, 85% and 80 % on Day 1 and Day 8 of Treatment | Day 8: SpO2 <85% | 0.162 percentage of TST | Standard Deviation 0.435 |
Comparison: Day 1: SpO2 is \<90%p-value: 0.47295% CI: [-0.558, 1.181]mixed effect model
Comparison: Day 1: SpO2 is \<85%p-value: 0.47995% CI: [-0.124, 0.258]mixed effect model
Comparison: Day 1: SpO2 is \<80%p-value: 0.85295% CI: [-0.019, 0.023]mixed effect model
Comparison: Day 8: SpO2 is \<90%p-value: 0.73395% CI: [-0.431, 0.607]mixed effect model
Comparison: Day 8: When SpO2 is \<85%p-value: 0.51895% CI: [-0.117, 0.228]mixed effect model
Comparison: Day 8: SpO2 is \<80%p-value: 0.57695% CI: [-0.015, 0.026]mixed effect model
Secondary
OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment
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.
Time frame: Day 1 and Day 8
Population: PD analysis set included group of participants who received at least 1 dose of study drug in each treatment periods and who had sufficient PD data to derive at least 1 primary PD parameter. Here, 'number analyzed' signifies participants who were evaluable for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HV Cohort: Placebo | OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment | Day 1 | 94.53 percentage of oxygen saturation | Standard Deviation 1.62 |
| HV Cohort: Placebo | OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment | Day 8 | 94.46 percentage of oxygen saturation | Standard Deviation 1.316 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment | Day 1 | 94.54 percentage of oxygen saturation | Standard Deviation 1.47 |
| HV Cohort: Lemborexant 10 mg | OSA Cohort: SpO2 During TST on Day 1 and Day 8 of Treatment | Day 8 | 94.65 percentage of oxygen saturation | Standard Deviation 1.539 |
Comparison: Day 1: Mean SpO2 during TSTp-value: 0.69995% CI: [-0.31, 0.46]mixed effect model
Comparison: Day 8: Mean SpO2 during TSTp-value: 0.16995% CI: [-0.11, 0.61]mixed effect model