Pulmonary Disease, Chronic Obstructive, Respiration Disorders, Sleep Apnea, Obstructive
Conditions
Keywords
E2006, Lemborexant, Peripheral Oxygen Saturation, Apnea Hypopnea Index
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.
Interventions
DRUGPlacebo
OSA: Lemborexant-matched oral placebo will be administered at bedtime in the clinic (within 5 minutes before lights off) or at home when not in the clinic.
OSA: 10 mg oral lemborexant will be administered at bedtime in the clinic (within 5 minutes before lights off) or at home when not in the clinic.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, age \>=45 and \<=90 at the time of informed consent 2. Voluntary agreement and ability to provide written informed consent 3. Body mass index (BMI) \<40 Kilogram per meter square (kg/m\^2) 4. Reports habitually sleeping for at least 5.5 hours per night 5. Reports habitual bedtime between 21:00 and midnight 6. Agrees to stay in bed for 7 hours per night for the duration of the study 7. At Screening Visit 2: Has completed the sleep diary for at least 5 consecutive nights 8. At Screening Visit 2: Confirmation of mean habitual bedtime (MHB) between 21:00 and midnight (sleep diary) Additional Inclusion Criteria (OSA Cohort) 9. 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 10. On screening PSG: moderate OSA (defined as 15 \<=AHI \<30) or severe OSA (defined as AHI \>=30 per hour) 11. SpO2 \>=94% assessed as part of vital signs at Screening Visit 1 Additional Inclusion Criteria (COPD Cohort) 12. Screening spirometry performed as per the Global Initiative for Obstructive Lung Disease (GOLD) recommendations 13. On screening spirometry, based on post-bronchodilator Forced Expiratory Volume in 1 second (FEV1): • FEV1/Forced Vital Capacity (FVC) \<0.70 and one of the following: * 50% \<=FEV1 \<80% predicted (GOLD 2 Classification for moderate COPD) or * 30% \<=FEV1 \<50% predicted (GOLD 3 Classification for severe COPD) 14. Moderate to severe COPD according to medical history and screening spirometry as per the GOLD criteria (GOLD 2019) 15. On screening PSG * AHI \<15 * SpO2 during wakefulness \>90% (both supine and sitting) * SpO2 during sleep \>=80% for at least 75% of the recording period with no more than five continuous minutes \<80% and with no SpO2 readings \<70%
Exclusion criteria
1. Females of childbearing potential 2. A current diagnosis of restless legs syndrome, periodic limb movement disorder, circadian rhythm sleep disorder, or narcolepsy 3. 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 4. 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 5. 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 6. A prolonged QT interval by Fredericia (QTcF) (QTcF \>450 milliseconds \[ms\]) as demonstrated by a repeated electrocardiogram (ECG) at Screening 7. 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 \[C-SSRS\]) 8. Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS) within 10 years of Screening 9. Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments 10. Hypersensitivity to the study drug or any of the excipients 11. Used any prohibited prescription or over-the-counter medications within 1 week or 5 half-lives, whichever is longer, before the screening PSG 12. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study 13. Scheduled for surgery during the study that requires general anesthesia or administration of prohibited medications 14. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years 15. History of drug or alcohol dependency or abuse within approximately the last 2 years 16. Use of illegal recreational drugs (includes marijuana, regardless of whether prescribed for medicinal use) 17. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5\*the half-life, whichever is longer preceding informed consent 18. Previously participated in other clinical trial of lemborexant 19. Exposure within the last 14 days to an individual with confirmed or probable corona virus disease 2019 (COVID-19) or symptoms within the last 14 days that are on the most recent Centers for Disease Control and Prevention (CDC) list of COVID symptoms or any other reason to consider the participant at potential risk for an acute COVID-19 infection Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment Periods 1 and 2 | 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). |
| COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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: 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) | ODI was defined as (oxygen desaturations \>=3%\*60)/TST (that is, the average number of oxygen desaturations \>=3% per hour of sleep), as defined by the American Academy of Sleep Medicine. TST was defined as the total time asleep in minutes using PSG. |
| 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) | Desaturation was defined as decrease in the mean SpO2 of \>=3% (over the last 120 seconds) that lasts for at least 10 seconds. 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. |
| 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) | 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 Periods 1 and 2 | Day 1 of Treatment Periods 1 and 2 (up to Day 23) | AHI was the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (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 \>=5 to \<15 is classed as mild, \>=15 to \<30 as moderate, and AHI \>=30 as severe. TST was defined as the total time asleep in minutes using PSG. |
| 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) | 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. |
| 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) | ODI was defined as (oxygen desaturations \>=3%\*60)/TST (that is, the average number of oxygen desaturations \>=3% per hour of sleep), as defined by the American Academy of Sleep Medicine. TST was defined as the total time asleep in minutes using PSG. |
| 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) | Desaturation was defined as decrease in the mean SpO2 of \>=3% (over the last 120 seconds) that lasts for at least 10 seconds. 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. |
| 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) | AHI was the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (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 \>=5 to \<15 is classed as mild, \>=15 to \<30 as moderate, and AHI \>=30 as severe. TST was defined as the total time asleep in minutes using PSG. |
| 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) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 10 investigative sites in the United States from 06 January 2021 to 10 February 2022.
Pre-assignment details
A total of 48 participants for the obstructive sleep apnea (OSA) cohort were screened, of which 15 were screen failures and 33 were randomized in OSA cohort to receive study treatment. A total of 108 participants were screened for the chronic obstructive pulmonary disease (COPD) cohort, of which 78 were screen failures and 30 were randomized in COPD cohort to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| OSA Cohort, Sequence A: Placebo + Lemborexant 10 mg Participants with OSA received lemborexant-matched placebo tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 1, followed by lemborexant 10 mg tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between both treatment periods. | 16 |
| OSA Cohort, Sequence B: Lemborexant 10 mg + Placebo Participants with OSA received lemborexant 10 mg tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 1, followed by one lemborexant-matched placebo tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between both treatment periods. | 17 |
| COPD Cohort, Sequence C: Placebo + Lemborexant 10 mg Participants with COPD received lemborexant-matched placebo tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 1, followed by lemborexant 10 mg tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between both treatment periods. | 14 |
| COPD Cohort, Sequence D: Lemborexant 10 mg + Placebo Participants with COPD received lemborexant 10 mg tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 1, followed by lemborexant-matched placebo tablet, orally, once daily on the night (within 5 minutes of lights off) of Day 1 through Day 8 of Treatment Period 2. A washout period of 14 days was maintained between both treatment periods. | 16 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 2 (8 Days) | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | OSA Cohort, Sequence A: Placebo + Lemborexant 10 mg | OSA Cohort, Sequence B: Lemborexant 10 mg + Placebo | COPD Cohort, Sequence C: Placebo + Lemborexant 10 mg | COPD Cohort, Sequence D: Lemborexant 10 mg + Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 11 Participants | 12 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 11 Participants | 3 Participants | 4 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 2 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 15 Participants | 12 Participants | 14 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 12 Participants | 13 Participants | 14 Participants | 51 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 11 Participants | 10 Participants | 31 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 3 Participants | 6 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 33 | 2 / 33 | 2 / 30 | 1 / 30 |
| serious Total, serious adverse events | 1 / 33 | 0 / 33 | 0 / 30 | 1 / 30 |
Outcome results
Primary
COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2
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 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OSA Cohort: Placebo | COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2 | 90.80 percentage of oxygen saturation | Standard Deviation 2.565 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Peripheral Oxygen Saturation (SpO2) During TST on Day 8 of Treatment Periods 1 and 2 | 91.27 percentage of oxygen saturation | Standard Deviation 2.227 |
Primary
OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment Periods 1 and 2
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).
Time frame: Day 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The pharmacodynamic (PD) analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OSA Cohort: Placebo | OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment Periods 1 and 2 | 45.09 events (apnea plus hyponea) per hour | Standard Deviation 22.851 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Apnea-Hypopnea Index (AHI) on Day 8 of Treatment Periods 1 and 2 | 44.90 events (apnea plus hyponea) per hour | Standard Deviation 22.246 |
Secondary
COPD Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2
Desaturation was defined as decrease in the mean SpO2 of \>=3% (over the last 120 seconds) that lasts for at least 10 seconds. 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: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | COPD Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 26.77 events (number of desaturations) | Standard Deviation 27.485 |
| OSA Cohort: Placebo | COPD Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 25.33 events (number of desaturations) | Standard Deviation 28.243 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 36.07 events (number of desaturations) | Standard Deviation 31.509 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 29.97 events (number of desaturations) | Standard Deviation 33.055 |
Secondary
COPD Cohort: AHI on Days 1 and 8 of Treatment Periods 1 and 2
AHI was the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (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 \>=5 to \<15 is classed as mild, \>=15 to \<30 as moderate, and AHI \>=30 as severe. TST was defined as the total time asleep in minutes using PSG.
Time frame: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | COPD Cohort: AHI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 6.09 events (apnea plus hyponea) per hour | Standard Deviation 4.827 |
| OSA Cohort: Placebo | COPD Cohort: AHI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 5.88 events (apnea plus hyponea) per hour | Standard Deviation 5.245 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: AHI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 7.40 events (apnea plus hyponea) per hour | Standard Deviation 6.331 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: AHI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 6.15 events (apnea plus hyponea) per hour | Standard Deviation 5.185 |
Secondary
COPD Cohort: Mean ODI on Days 1 and 8 of Treatment Periods 1 and 2
ODI was defined as (oxygen desaturations \>=3%\*60)/TST (that is, the average number of oxygen desaturations \>=3% per hour of sleep), as defined by the American Academy of Sleep Medicine. TST was defined as the total time asleep in minutes using PSG.
Time frame: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | COPD Cohort: Mean ODI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 4.61 events per hour | Standard Deviation 4.462 |
| OSA Cohort: Placebo | COPD Cohort: Mean ODI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 4.34 events per hour | Standard Deviation 4.562 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Mean ODI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 5.46 events per hour | Standard Deviation 4.823 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Mean ODI on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 4.71 events per hour | Standard Deviation 4.772 |
Secondary
COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2
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: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <90% | 15.593 percentage of TST | Standard Deviation 23.3552 |
| OSA Cohort: Placebo | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <85% | 0.860 percentage of TST | Standard Deviation 1.9286 |
| OSA Cohort: Placebo | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <80% | 0.155 percentage of TST | Standard Deviation 0.5416 |
| OSA Cohort: Placebo | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <90% | 22.991 percentage of TST | Standard Deviation 30.9595 |
| OSA Cohort: Placebo | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <85% | 3.330 percentage of TST | Standard Deviation 9.9935 |
| OSA Cohort: Placebo | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <80% | 0.152 percentage of TST | Standard Deviation 0.4743 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <85% | 1.151 percentage of TST | Standard Deviation 3.1124 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <90% | 21.468 percentage of TST | Standard Deviation 30.0042 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <90% | 21.086 percentage of TST | Standard Deviation 30.356 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <85% | 3.286 percentage of TST | Standard Deviation 9.019 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <80% | 0.075 percentage of TST | Standard Deviation 0.2218 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Percentage of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <80% | 0.224 percentage of TST | Standard Deviation 0.5912 |
Secondary
COPD Cohort: Peripheral SpO2 During TST on Day 1 of Treatment Periods 1 and 2
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 of Treatment Periods 1 and 2 (up to Day 23)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OSA Cohort: Placebo | COPD Cohort: Peripheral SpO2 During TST on Day 1 of Treatment Periods 1 and 2 | 91.53 percentage of oxygen saturation | Standard Deviation 2.161 |
| OSA Cohort: Lemborexant 10 mg | COPD Cohort: Peripheral SpO2 During TST on Day 1 of Treatment Periods 1 and 2 | 91.13 percentage of oxygen saturation | Standard Deviation 2.801 |
Secondary
OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2
Desaturation was defined as decrease in the mean SpO2 of \>=3% (over the last 120 seconds) that lasts for at least 10 seconds. 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: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter. Here, number analyzed signifies those participants who were evaluable at given timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 253.85 events (number of desaturations) | Standard Deviation 161.971 |
| OSA Cohort: Placebo | OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 255.28 events (number of desaturations) | Standard Deviation 149.158 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 256.52 events (number of desaturations) | Standard Deviation 141.952 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Absolute Number of Desaturations (>=3% Reduction From Baseline SpO2) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 273.97 events (number of desaturations) | Standard Deviation 155.209 |
Secondary
OSA Cohort: AHI on Day 1 of Treatment Periods 1 and 2
AHI was the number of apneas and hypopneas divided by the TST (in minutes) and multiplied by 60 (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 \>=5 to \<15 is classed as mild, \>=15 to \<30 as moderate, and AHI \>=30 as severe. TST was defined as the total time asleep in minutes using PSG.
Time frame: Day 1 of Treatment Periods 1 and 2 (up to Day 23)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OSA Cohort: Placebo | OSA Cohort: AHI on Day 1 of Treatment Periods 1 and 2 | 44.65 events (apnea plus hyponea) per hour | Standard Deviation 25.77 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: AHI on Day 1 of Treatment Periods 1 and 2 | 41.64 events (apnea plus hyponea) per hour | Standard Deviation 21.215 |
Secondary
OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2
ODI was defined as (oxygen desaturations \>=3%\*60)/TST (that is, the average number of oxygen desaturations \>=3% per hour of sleep), as defined by the American Academy of Sleep Medicine. TST was defined as the total time asleep in minutes using PSG.
Time frame: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter. Here, number analyzed signifies those participants who were evaluable at given timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 39.71 events per hour | Standard Deviation 24.547 |
| OSA Cohort: Placebo | OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 39.07 events per hour | Standard Deviation 21.475 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 36.52 events per hour | Standard Deviation 20.325 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Mean Oxygen Desaturation Index (ODI) on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 39.51 events per hour | Standard Deviation 22.037 |
Secondary
OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2
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: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter. Here, number analyzed signifies those participants who were evaluable at given timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <85% | 2.708 percentage of TST | Standard Deviation 4.94 |
| OSA Cohort: Placebo | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <90% | 11.966 percentage of TST | Standard Deviation 16.8941 |
| OSA Cohort: Placebo | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <85% | 2.283 percentage of TST | Standard Deviation 3.6302 |
| OSA Cohort: Placebo | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <80% | 0.776 percentage of TST | Standard Deviation 1.7896 |
| OSA Cohort: Placebo | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <80% | 0.522 percentage of TST | Standard Deviation 1.3345 |
| OSA Cohort: Placebo | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <90% | 9.474 percentage of TST | Standard Deviation 9.793 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <80% | 0.651 percentage of TST | Standard Deviation 1.3153 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <90% | 12.849 percentage of TST | Standard Deviation 15.5993 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <85% | 3.748 percentage of TST | Standard Deviation 6.601 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1: SpO2 <80% | 1.125 percentage of TST | Standard Deviation 2.5021 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <90% | 11.295 percentage of TST | Standard Deviation 12.6345 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Percentage (%) of TST During Which SpO2 Was <90%, <85% and <80% on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8: SpO2 <85% | 2.696 percentage of TST | Standard Deviation 4.4283 |
Secondary
OSA Cohort: Peripheral SpO2 During TST on Days 1 and 8 of Treatment Periods 1 and 2
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: Days 1 and 8 of Treatment Periods 1 and 2 (up to Day 30)
Population: The PD analysis set for each cohort was the group of participants who had sufficient PD data to derive at least 1 primary PD parameter. Here, number analyzed signifies those participants who were evaluable at given timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OSA Cohort: Placebo | OSA Cohort: Peripheral SpO2 During TST on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 93.12 percentage of oxygen saturation | Standard Deviation 2.073 |
| OSA Cohort: Placebo | OSA Cohort: Peripheral SpO2 During TST on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 93.44 percentage of oxygen saturation | Standard Deviation 1.983 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Peripheral SpO2 During TST on Days 1 and 8 of Treatment Periods 1 and 2 | Day 1 | 93.00 percentage of oxygen saturation | Standard Deviation 2.462 |
| OSA Cohort: Lemborexant 10 mg | OSA Cohort: Peripheral SpO2 During TST on Days 1 and 8 of Treatment Periods 1 and 2 | Day 8 | 93.06 percentage of oxygen saturation | Standard Deviation 1.983 |