Insomnia
Conditions
Keywords
E2006, Lemborexant, zolpidem tartrate, Ambien CR, Insomnia
Brief summary
This study will be conducted to demonstrate, using polysomnography, that lemborexant 10 milligrams (mg) and 5 mg is superior to placebo on objective sleep onset as assessed by latency to persistent to sleep (LPS) after the last 2 nights of 1 month of treatment in participants 55 years and older with insomnia disorder.
Detailed description
The study is a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study of 2 dose levels of lemborexant for 30 nights in approximately 950 participants, 55 years or older with insomnia disorder. Participants will be males 65 years or older or females 55 years or older. Approximately 60% of the participants will be age 65 years or older. The study will have 2 phases: The Prerandomization Phase and the Randomization Phase. Including both phases, the study will last for a minimum of 65 and a maximum of 81 days per participant.
Interventions
DRUGLemborexant
Lemborexant 5 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
Lemborexant-matched placebo be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
Zolpidem tartrate extended release 6.25 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
DRUGZolpidem-matched placebo
Zolpidem-matched placebo will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male age 65 years or older or female age 55 years or older at the time of informed consent 2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for Insomnia Disorder, as follows: * Complains of dissatisfaction with nighttime sleep, in the form of difficulty staying asleep and/or awakening earlier in the morning than desired despite adequate opportunity for sleep (Note that if the complaint is limited to difficulty initiating sleep, the participant is not eligible) * Frequency of complaint ≥ 3 times per week * Duration of complaint ≥ 3 months * Associated with complaint of daytime impairment 3. History of subjective wake after sleep onset (sWASO) typically ≥ 60 minutes on at least 3 nights per week in the previous 4 weeks 4. Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours 5. Reports habitual bedtime, defined as the time the participant attempts to sleep, between 21:00 and 24:00 and habitual waketime between 05:00 and 09:00 6. Insomnia Severity Index (ISI) score ≥ 13 7. Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary before the second screening visit 8. Confirmation of regular bedtime and waketime as determined from responses on the Sleep Diary 9. Confirmation of sufficient duration of time spent in bed, as determined from responses on the Sleep Diary 10. Objective (polysomnography \[PSG\]) evidence of insomnia as follows: a) Wake after sleep onset (WASO) average ≥ 60 minutes on the 2 consecutive PSGs, with neither night \< 45 minutes 11. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night 12. Willing not to start a behavioral or other treatment program for the treatment of insomnia during the participant's participation in the study
Exclusion criteria
1. A current diagnosis of sleep-related breathing disorder including obstructive sleep apnea (with or without continuous positive airway pressure \[CPAP\] treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows: 1. STOPBang score ≥5 2. International Restless Legs Scale score ≥16 3. Epworth Sleepiness Scale score \>15 (scores of 11 to 15 require excessive daytime sleepiness to be recorded in participant's Medical History) 2. Reports symptoms potentially related to narcolepsy, that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy 3. On the Munich Parasomnia Scale (MUPS), endorsed the item that corresponds to a history of sleep-eating or reports a history of sleep-related violent behavior, sleep-driving, or symptoms of another parasomnia that in the investigator's opinion make the participant unsuitable for the study 4. Apnea-Hypopnea Index \> 15 or Periodic Limb Movement with Arousal Index \>15 as measured on the PSG at the second screening visit 5. Beck Depression Inventory - II (BDI-II) score \>19 at Screening 6. Beck Anxiety Index (BAI) score \>15 at Screening 7. Habitually naps during the day more than 3 times per week 8. Is a female of childbearing potential Note: All females will be considered to be of childbearing potential unless they are postmenopausal (defined as amenorrheic for at least 12 consecutive months, and are postmenopausal without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). 9. Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or habitually consumes caffeine-containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study. 10. History of drug or alcohol dependency or abuse within approximately the previous 2 years 11. Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males), or unwilling to limit alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3 hours before bedtime for the duration of his/her participation in the study 12. Known to be positive for human immunodeficiency virus 13. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening 14. A prolonged QT/QTcF interval (QTcF \>450 milliseconds \[ms\]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval \>450 ms) 15. Current evidence of clinically significant disease (e.g., cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; gastrointestinal; severe hepatic impairment; renal including severe renal impairment; neurological including myasthenia gravis; psychiatric disease; or malignancy within the past 5 years other than adequately treated basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments, including the ability to perform tasks on the cognitive performance assessment battery (PAB). Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded. 16. Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night 17. Any history of a medical or psychiatric condition that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessment, including the ability to perform the PAB. 18. Any suicidal ideation with intent with or without a plan, at the time of or within 6 months before the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) administration during the Prerandomization Phase (i.e., answering Yes to questions 4 or 5 on the Suicidal Ideation section of the eC-SSRS) 19. Any suicidal behavior in the past 10 years (per the Suicidal Behavior section of the eC-SSRS) 20. Scheduled for surgery during the study 21. Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half lives, whichever is longer, before the first dose of study medication (Run-in Period). 22. Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 1 week or 5 half-lives, whichever is longer, before the first dose of study medication (Run-in Period) 23. Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator 24. Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Baseline, or plans to travel across more than 3 time zones during the study 25. A positive drug test at Screening, Run-In, or Baseline, or unwilling to refrain from use of recreational drugs during the study 26. Hypersensitivity to lemborexant or zolpidem or to their excipients 27. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5× the half-life, whichever is longer preceding informed consent 28. Previously participated in any clinical trial of lemborexant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline, Days 29/30 | LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by PSG. Change from baseline to average LPS on Day 29 and 30 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline, Days 29/30 | SE is defined as percentage of time spent in bed asleep, calculated as total sleep time (TST) divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 29 and 30 was reported. |
| Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline, Days 29/30 | WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. Change from baseline to average WASO on Days 29 and 30 was reported. |
| Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Baseline, Days 29/30 | WASO2H is defined as time in minutes of wake during the interval from 240 minutes after lights off until lights on as measured by PSG. Change from baseline to average WASO2H on Days 29 and 30 was reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | Baseline, Days 1/2 | LPS: amount of time in minutes from lights off to first epoch of 20 consecutive epochs of non-wakefulness. WASO: amount of time in minutes of wake from the onset of persistent sleep until lights. WASO2H: amount of time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST: amount of time in minutes of sleep from sleep onset until terminal awakening. LPS, WASO, WASO2H, and TST were measured by PSG. Change from baseline to average LPS, WASO, WASO2H, and TST on Day 1 and 2 were reported. |
| Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | Baseline, Days 1/2 | SE is defined as percentage of time spent in bed asleep, calculated as TST divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 1 and 2 were reported. |
| Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline, Days 29/30 | WASO2H is defined as the time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST is defined as the amount of sleep in minutes from sleep onset until terminal awakening. WASO and TST were measured by PSG. Change from baseline to average WASO and TST on Day 29 and 30 were reported. |
| Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4) | sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. |
| Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4) | sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. |
| Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Baseline, Days 2/3 | Body sway is detected through a cable around the participant's waist by the ataxia meter. Body sway is measured in units of one-third degree of the angle of arc. For ease in reporting, these are called arbitrary units, with a higher number indicating more body sway (less postural stability). Change from baseline in mean body sway on Days 2 and 3 was reported. |
| Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline and Day 31 | The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: severity of sleep onset; sleep maintenance; early morning awakening problems; sleep dissatisfaction; interference of sleep difficulties with daytime functioning; noticeability of the sleep problems by others; and distress caused by the sleep difficulties. A 5-point Likert scale was used to rate each item (from 0 = no problem to 4 = very severe problem) yielding a total score from 0 to 28. |
| Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline and Day 31 | The FSS is a self-report scale on which participants are instructed to choose a number from 1 to 7 that indicates their degree of agreement with each of 9 statements about their fatigue where 1 indicates strongly disagree, and 7 indicates strongly agree. The FSS total score was the sum of all responses to the 9 questions. The FSS average item score was the average of the score for each item. Higher total scores and higher average item scores indicated greater fatigue. |
| Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | Baseline, Days 2/3 | POA reflects the ability to focus attention and process information. POA is calculated from the sum of simple reaction time, choice reaction time and digit vigilance. SOMT reflects time taken to retrieve information from working and episodic memory. SOMT is a composite score created by combining numerical working memory and spatial working memory and word recognition and picture recognition. Cognitive performance assessment was done by a computerized performance assessment battery (PAB) which was administered on a laptop computer. A positive change from baseline reflects impairment and a lower value of decrease from baseline indicates better performance. Change from baseline to average POA and SOMT on Days 2 and 3 was reported. |
| Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | Baseline, Days 2/3 | QOM represents the ability to store information in memory and subsequently retrieve it. It is a composite score created by combining accuracy measures from 2 sets of working memory and 4 sets of episodic memory. Two sets of working memory were included: numerical and spatial working memory, and ranges from -2 to 2. Four sets of episodic memory were included: immediate and delayed word recall, and word and picture recognition, and ranges from -200 to 400. COA is the ability to sustain attention. Number of correct responses (out of 50) for choice reaction time was added to total number of targets correctly identified (out of 45) digit vigilance minus number of false alarms (total score of -45 to 95). Higher values were better. Change from baseline to average QOM and COA on Days 2 and 3 was reported. |
| Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | Days 1/2, Days 29/30, first 7 night (approximately Week 1), and Last seven nights (approximately Week 4) | Objective sleep onset response: LPS less than or equal to (\<=) 20 minutes (mins) provided baseline LPS was greater than (\>) 30 mins. Subjective sleep onset response: sSOL \<=20 mins provided mean baseline sSOL was \>30 mins. Objective sleep maintenance response: WASO \<=60 minutes provided baseline WASO was \>60 mins and was reduced by \>10 mins compared to baseline. Subjective sleep maintenance response: sWASO \<=60 mins provided mean WASO was \>60 mins and was reduced by \>10 mins compared to baseline. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. Average data for Days 1 and 2, Days 29 and 30, and first and last 7 nights of treatment period was reported. |
| Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | Baseline, Days 1/2, and Days 29/30 | LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by the PSG. WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. TST is defined as the amount of sleep in minutes from LPS until terminal awakening as measured by PSG. Change from baseline to average LPS, WASO, and TST on Days 1 and 2, and Days 29 and 30 were reported. |
| Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4) | sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with diary handling rules (DHR) on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. |
| Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4) | sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. |
Countries
Canada, France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 67 investigative sites in the United States, Spain, Germany, Canada, United Kingdom, and Italy from 31 May 2016 to 30 January 2018.
Pre-assignment details
A total of 3537 participants were screened, of which 1006 participants were randomized to the treatment period. All participants who were subsequently randomized completed a Run-in Period before randomization to treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. | 208 |
| Zolpidem Tartrate Extended Release 6.25 mg Participants received zolpidem tartrate extended release (ZOL ER) 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period. | 263 |
| Lemborexant 5 mg Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. | 266 |
| Lemborexant 10 mg Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. | 269 |
| Total | 1,006 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 6 | 2 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 1 | 0 |
| Overall Study | Other | 1 | 6 | 2 | 3 |
| Overall Study | Participant's choice | 2 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Lemborexant 10 mg | Lemborexant 5 mg | Zolpidem Tartrate Extended Release 6.25 mg | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 6.81 | 64.2 years STANDARD_DEVIATION 6.88 | 63.7 years STANDARD_DEVIATION 6.78 | 64.3 years STANDARD_DEVIATION 7.12 | 63.4 years STANDARD_DEVIATION 6.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 165 Participants | 47 Participants | 51 Participants | 32 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 841 Participants | 222 Participants | 215 Participants | 231 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 256 Participants | 62 Participants | 63 Participants | 80 Participants | 51 Participants |
| Race/Ethnicity, Customized Chinese | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Japanese | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Other Asian | 10 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 727 Participants | 202 Participants | 199 Participants | 173 Participants | 153 Participants |
| Sex: Female, Male Female | 869 Participants | 230 Participants | 229 Participants | 226 Participants | 184 Participants |
| Sex: Female, Male Male | 137 Participants | 39 Participants | 37 Participants | 37 Participants | 24 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 / 209 | 0 / 263 | 0 / 266 | 0 / 268 | 0 / 1,006 |
| other Total, other adverse events | 16 / 209 | 18 / 263 | 27 / 266 | 28 / 268 | 34 / 1,006 |
| serious Total, serious adverse events | 0 / 209 | 4 / 263 | 2 / 266 | 0 / 268 | 0 / 1,006 |
Outcome results
Primary
Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by PSG. Change from baseline to average LPS on Day 29 and 30 was reported.
Time frame: Baseline, Days 29/30
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 43.89 minutes | Standard Deviation 33.596 |
| Placebo | Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | -7.93 minutes | Standard Deviation 31.946 |
| Lemborexant 5 mg | Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 44.86 minutes | Standard Deviation 36.528 |
| Lemborexant 5 mg | Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | -19.53 minutes | Standard Deviation 33.054 |
| Lemborexant 10 mg | Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 44.61 minutes | Standard Deviation 32.986 |
| Lemborexant 10 mg | Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | -21.46 minutes | Standard Deviation 32.436 |
p-value: =0.000395% CI: [0.672, 0.889]MMRM
p-value: <0.000195% CI: [0.628, 0.832]MMRM
Secondary
Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
SE is defined as percentage of time spent in bed asleep, calculated as total sleep time (TST) divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 29 and 30 was reported.
Time frame: Baseline, Days 29/30
Population: The FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 68.89 Percentage of time in bed asleep | Standard Deviation 9.639 |
| Placebo | Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | 5.35 Percentage of time in bed asleep | Standard Deviation 9.897 |
| Lemborexant 5 mg | Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 68.36 Percentage of time in bed asleep | Standard Deviation 11.268 |
| Lemborexant 5 mg | Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | 12.93 Percentage of time in bed asleep | Standard Deviation 9.741 |
| Lemborexant 10 mg | Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 67.85 Percentage of time in bed asleep | Standard Deviation 10.849 |
| Lemborexant 10 mg | Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | 14.09 Percentage of time in bed asleep | Standard Deviation 10.514 |
p-value: <0.000195% CI: [5.61, 8.54]MMRM
p-value: <0.000195% CI: [6.57, 9.49]MMRM
Secondary
Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. Change from baseline to average WASO on Days 29 and 30 was reported.
Time frame: Baseline, Days 29/30
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 111.75 minutes | Standard Deviation 37.179 |
| Placebo | Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | -18.58 minutes | Standard Deviation 41.931 |
| Lemborexant 5 mg | Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 113.44 minutes | Standard Deviation 38.953 |
| Lemborexant 5 mg | Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | -43.89 minutes | Standard Deviation 39.264 |
| Lemborexant 10 mg | Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Baseline | 114.83 minutes | Standard Deviation 39.997 |
| Lemborexant 10 mg | Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | Change at Days 29/30 | -46.43 minutes | Standard Deviation 39.595 |
p-value: <0.000195% CI: [-29.98, -17.95]MMRM
p-value: <0.000195% CI: [-31.36, -19.34]MMRM
Secondary
Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30
WASO2H is defined as time in minutes of wake during the interval from 240 minutes after lights off until lights on as measured by PSG. Change from baseline to average WASO2H on Days 29 and 30 was reported.
Time frame: Baseline, Days 29/30
Population: FAS was the group of randomized Participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Baseline | 78.04 minutes | Standard Deviation 33.849 |
| Placebo | Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Change at Days 29/30 | -21.42 minutes | Standard Deviation 36.257 |
| Lemborexant 5 mg | Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Change at Days 29/30 | -27.19 minutes | Standard Deviation 33.047 |
| Lemborexant 5 mg | Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Baseline | 76.60 minutes | Standard Deviation 32.903 |
| Lemborexant 10 mg | Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Baseline | 76.88 minutes | Standard Deviation 32.126 |
| Lemborexant 10 mg | Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30 | Change at Days 29/30 | -28.84 minutes | Standard Deviation 33.138 |
p-value: =0.003895% CI: [-11.15, -2.15]MMRM
p-value: =0.000595% CI: [-12.53, -3.47]MMRM
Other Pre-specified
Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31
The FSS is a self-report scale on which participants are instructed to choose a number from 1 to 7 that indicates their degree of agreement with each of 9 statements about their fatigue where 1 indicates strongly disagree, and 7 indicates strongly agree. The FSS total score was the sum of all responses to the 9 questions. The FSS average item score was the average of the score for each item. Higher total scores and higher average item scores indicated greater fatigue.
Time frame: Baseline and Day 31
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 37.48 score on scale | Standard Deviation 13.602 |
| Placebo | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -6.75 score on scale | Standard Deviation 11.916 |
| Lemborexant 5 mg | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -7.80 score on scale | Standard Deviation 12.879 |
| Lemborexant 5 mg | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 37.15 score on scale | Standard Deviation 13.788 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 37.47 score on scale | Standard Deviation 13.518 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -8.14 score on scale | Standard Deviation 13.411 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 37.42 score on scale | Standard Deviation 13.111 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -8.00 score on scale | Standard Deviation 14.058 |
Comparison: Placebo, Lemborexant 5 mgp-value: =0.234895% CI: [-3.35, 0.82]ANCOVA
Comparison: Placebo, Lemborexant 10 mgp-value: =0.274595% CI: [-3.26, 0.93]ANCOVA
Comparison: Zolpidem ER, Lemborexant 5 mgp-value: =0.71195% CI: [-2.35, 1.6]ANCOVA
Comparison: Zolpidem ER, Lemborexant 10 mgp-value: =0.785495% CI: [-2.26, 1.71]ANCOVA
Other Pre-specified
Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3
Body sway is detected through a cable around the participant's waist by the ataxia meter. Body sway is measured in units of one-third degree of the angle of arc. For ease in reporting, these are called arbitrary units, with a higher number indicating more body sway (less postural stability). Change from baseline in mean body sway on Days 2 and 3 was reported.
Time frame: Baseline, Days 2/3
Population: The FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Baseline | 26.96 one-third degree of angle of arc | Standard Deviation 26.502 |
| Placebo | Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Change at Days 2/3 | 8.47 one-third degree of angle of arc | Standard Deviation 69.894 |
| Lemborexant 5 mg | Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Baseline | 26.40 one-third degree of angle of arc | Standard Deviation 20.781 |
| Lemborexant 5 mg | Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Change at Days 2/3 | -0.82 one-third degree of angle of arc | Standard Deviation 20.383 |
| Lemborexant 10 mg | Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Baseline | 36.29 one-third degree of angle of arc | Standard Deviation 197.282 |
| Lemborexant 10 mg | Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3 | Change at Days 2/3 | -8.97 one-third degree of angle of arc | Standard Deviation 146.679 |
Comparison: Zolpidem Tartrate Extended Release 6.25 mg v Lemborexant 5 mgp-value: =0.017195% CI: [-17.53, -1.72]MMRM
Comparison: Zolpidem Tartrate Extended Release 6.25 mg v Lemborexant 10 mgp-value: =0.00895% CI: [-18.67, -2.81]MMRM
Other Pre-specified
Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30
LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by the PSG. WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. TST is defined as the amount of sleep in minutes from LPS until terminal awakening as measured by PSG. Change from baseline to average LPS, WASO, and TST on Days 1 and 2, and Days 29 and 30 were reported.
Time frame: Baseline, Days 1/2, and Days 29/30
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Baseline | 114.31 minutes | Standard Deviation 39.992 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Change at Days 29/30 | 43.34 minutes | Standard Deviation 54.012 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Change at Days 29/30 | -36.50 minutes | Standard Deviation 43.406 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Change at Days 1/2 | -44.36 minutes | Standard Deviation 38.074 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Baseline | 44.52 minutes | Standard Deviation 38.349 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Change at Days 1/2 | 55.31 minutes | Standard Deviation 48.138 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Change at Days 29/30 | -7.51 minutes | Standard Deviation 35.065 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Change at Days 1/2 | -12.56 minutes | Standard Deviation 32.506 |
| Placebo | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Baseline | 326.99 minutes | Standard Deviation 54.852 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Change at Days 1/2 | -49.96 minutes | Standard Deviation 39.578 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Baseline | 44.86 minutes | Standard Deviation 36.528 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Change at Days 1/2 | -16.59 minutes | Standard Deviation 28.742 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Change at Days 29/30 | -19.53 minutes | Standard Deviation 33.054 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Baseline | 113.44 minutes | Standard Deviation 38.953 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Change at Days 29/30 | -43.89 minutes | Standard Deviation 39.264 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Baseline | 328.00 minutes | Standard Deviation 54.224 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Change at Days 1/2 | 65.22 minutes | Standard Deviation 46.695 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Change at Days 29/30 | 61.99 minutes | Standard Deviation 46.817 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Change at Days 29/30 | -21.46 minutes | Standard Deviation 32.436 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Baseline | 44.61 minutes | Standard Deviation 32.986 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Baseline | 325.07 minutes | Standard Deviation 52.819 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | LPS: Change at Days 1/2 | -19.48 minutes | Standard Deviation 31.809 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Change at Days 29/30 | 67.86 minutes | Standard Deviation 52.117 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Change at Days 1/2 | -59.59 minutes | Standard Deviation 37.749 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Baseline | 114.83 minutes | Standard Deviation 39.997 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | TST: Change at Days 1/2 | 79.58 minutes | Standard Deviation 47.35 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30 | WASO: Change at Days 29/30 | -46.43 minutes | Standard Deviation 39.595 |
Comparison: LPS, Days 1/2: Zolpidem ER, Lemborexant 5 mgp-value: =0.021895% CI: [0.78, 0.981]MMRM
Comparison: LPS, Days 1/2: Zolpidem ER, Lemborexant 10 mgp-value: =0.000695% CI: [0.729, 0.917]MMRM
Comparison: LPS, Days 29/30: Zolpidem ER, Lemborexant 5 mgp-value: <0.000195% CI: [0.556, 0.724]MMRM
Comparison: LPS, Days 29/30: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [0.521, 0.677]MMRM
Comparison: WASO, Days 1/2: Zolpidem ER, Lemborexant 5 mgp-value: =0.015495% CI: [-11.15, -1.17]MMRM
Comparison: WASO, Days 1/2: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [-20.01, -10.05]MMRM
Comparison: WASO, Days 29/30: Zolpidem ER, Lemborexant 5 mgp-value: =0.007395% CI: [-13.36, -2.08]MMRM
Comparison: WASO, Days 29/30: Zolpidem ER, Lemborexant 10 mgp-value: =0.001695% CI: [-14.75, -3.45]MMRM
Comparison: TST, Days 1/2: Zolpidem ER, Lemborexant 5 mgp-value: =0.00195% CI: [4.18, 16.32]MMRM
Comparison: TST, Days 1/2: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [17.04, 29.15]MMRM
Comparison: TST, Days 29/30: Zolpidem ER, Lemborexant 5 mgp-value: <0.000195% CI: [12.63, 26.2]MMRM
Comparison: TST, Days 29/30: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [17.32, 30.88]MMRM
Other Pre-specified
Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
LPS: amount of time in minutes from lights off to first epoch of 20 consecutive epochs of non-wakefulness. WASO: amount of time in minutes of wake from the onset of persistent sleep until lights. WASO2H: amount of time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST: amount of time in minutes of sleep from sleep onset until terminal awakening. LPS, WASO, WASO2H, and TST were measured by PSG. Change from baseline to average LPS, WASO, WASO2H, and TST on Day 1 and 2 were reported.
Time frame: Baseline, Days 1/2
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | LPS: Baseline | 43.89 minutes | Standard Deviation 33.596 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | LPS: Change at Days 1/2 | -6.45 minutes | Standard Deviation 32.618 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO: Baseline | 111.75 minutes | Standard Deviation 37.179 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO: Change at Days 1/2 | -15.07 minutes | Standard Deviation 36.938 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO2H: Baseline | 74.44 minutes | Standard Deviation 30.109 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO2H: Change at Days 1/2 | -7.06 minutes | Standard Deviation 31.097 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | TST: Baseline | 330.67 minutes | Standard Deviation 46.268 |
| Placebo | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | TST: Change at Days 1/2 | 19.44 minutes | Standard Deviation 43.348 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO: Baseline | 113.44 minutes | Standard Deviation 38.953 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | TST: Baseline | 328.00 minutes | Standard Deviation 54.224 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO: Change at Days 1/2 | -49.96 minutes | Standard Deviation 39.578 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO2H: Baseline | 76.60 minutes | Standard Deviation 32.903 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO2H: Change at Days 1/2 | -30.28 minutes | Standard Deviation 32.056 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | LPS: Baseline | 44.86 minutes | Standard Deviation 36.528 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | LPS: Change at Days 1/2 | -16.59 minutes | Standard Deviation 28.742 |
| Lemborexant 5 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | TST: Change at Days 1/2 | 65.22 minutes | Standard Deviation 46.695 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO: Baseline | 114.83 minutes | Standard Deviation 39.997 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | LPS: Change at Days 1/2 | -19.48 minutes | Standard Deviation 31.809 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | LPS: Baseline | 44.61 minutes | Standard Deviation 32.986 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO: Change at Days 1/2 | -59.59 minutes | Standard Deviation 37.749 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | TST: Baseline | 325.07 minutes | Standard Deviation 52.819 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO2H: Change at Days 1/2 | -37.10 minutes | Standard Deviation 30.815 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | WASO2H: Baseline | 76.88 minutes | Standard Deviation 32.126 |
| Lemborexant 10 mg | Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | TST: Change at Days 1/2 | 79.58 minutes | Standard Deviation 47.35 |
Comparison: LPS: Placebo, Lemborexant 5 mgp-value: =0.009295% CI: [0.752, 0.961]MMRM
Comparison: LPS: Placebo, Lemborexant 10 mgp-value: =0.000295% CI: [0.704, 0.899]MMRM
Comparison: WASO: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [-38.71, -28.09]MMRM
Comparison: WASO: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [-47.57, -36.97]MMRM
Comparison: WASO2H: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [-26.01, -17.3]MMRM
Comparison: WASO2H: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [-32.68, -23.98]MMRM
Comparison: TST: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [37.59, 50.51]MMRM
Comparison: TST: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [50.46, 63.34]MMRM
Other Pre-specified
Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3
POA reflects the ability to focus attention and process information. POA is calculated from the sum of simple reaction time, choice reaction time and digit vigilance. SOMT reflects time taken to retrieve information from working and episodic memory. SOMT is a composite score created by combining numerical working memory and spatial working memory and word recognition and picture recognition. Cognitive performance assessment was done by a computerized performance assessment battery (PAB) which was administered on a laptop computer. A positive change from baseline reflects impairment and a lower value of decrease from baseline indicates better performance. Change from baseline to average POA and SOMT on Days 2 and 3 was reported.
Time frame: Baseline, Days 2/3
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA: Baseine | 1421.0 millisecond | Standard Deviation 210.27 |
| Placebo | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA : Days 2/3 | -14.2 millisecond | Standard Deviation 149.31 |
| Placebo | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Baseline | 4507.7 millisecond | Standard Deviation 1098.73 |
| Placebo | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Days 2/3 | -177.9 millisecond | Standard Deviation 668.77 |
| Lemborexant 5 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Days 2/3 | 60.7 millisecond | Standard Deviation 749.12 |
| Lemborexant 5 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Baseline | 4513.8 millisecond | Standard Deviation 1097.65 |
| Lemborexant 5 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA : Days 2/3 | 37.1 millisecond | Standard Deviation 107.15 |
| Lemborexant 5 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA: Baseine | 1418.7 millisecond | Standard Deviation 195.95 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Baseline | 4674.3 millisecond | Standard Deviation 1174.74 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Days 2/3 | -185.1 millisecond | Standard Deviation 645.18 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA : Days 2/3 | 8.9 millisecond | Standard Deviation 154.33 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA: Baseine | 1452.9 millisecond | Standard Deviation 263.04 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Days 2/3 | -152.8 millisecond | Standard Deviation 722.49 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA: Baseine | 1399.2 millisecond | Standard Deviation 192.47 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | POA : Days 2/3 | 31.1 millisecond | Standard Deviation 142.38 |
| Lemborexant 10 mg | Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3 | SOMT: Baseline | 4619.8 millisecond | Standard Deviation 1065 |
Comparison: POA: Placebo, Lemborexant 5 mgp-value: =0.014195% CI: [6.23, 55.31]MMRM
Comparison: POA: Placebo, Lemborexant 10 mgp-value: =0.001695% CI: [15.05, 64.29]MMRM
Comparison: POA: Zolpidem ER, Lemborexant 5 mgp-value: =0.103195% CI: [-42.34, 3.9]MMRM
Comparison: POA: Zolpidem ER, Lemborexant 10 mgp-value: =0.382595% CI: [-33.5, 12.86]MMRM
Comparison: SOMT: Placebo, Lemborexant 5 mgp-value: =0.634895% CI: [-90.18, 147.8]MMRM
Comparison: SOMT: Placebo, Lemborexant 10 mgp-value: =0.402695% CI: [-68.3, 169.97]MMRM
Comparison: SOMT: Zolpidem ER, Lemborexant 5 mgp-value: =0.000495% CI: [-315.56, -91.15]MMRM
Comparison: SOMT: Zolpidem ER, Lemborexant 10 mgp-value: =0.001695% CI: [-293.71, -68.96]MMRM
Other Pre-specified
Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3
QOM represents the ability to store information in memory and subsequently retrieve it. It is a composite score created by combining accuracy measures from 2 sets of working memory and 4 sets of episodic memory. Two sets of working memory were included: numerical and spatial working memory, and ranges from -2 to 2. Four sets of episodic memory were included: immediate and delayed word recall, and word and picture recognition, and ranges from -200 to 400. COA is the ability to sustain attention. Number of correct responses (out of 50) for choice reaction time was added to total number of targets correctly identified (out of 45) digit vigilance minus number of false alarms (total score of -45 to 95). Higher values were better. Change from baseline to average QOM and COA on Days 2 and 3 was reported.
Time frame: Baseline, Days 2/3
Population: FAS was group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Baseline | 342.2 units on scale | Standard Deviation 66.03 |
| Placebo | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Change at Days 2/3 | 3.5 units on scale | Standard Deviation 45.2 |
| Placebo | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Baseline | 90.7 units on scale | Standard Deviation 4.77 |
| Placebo | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Change at Days2/3 | 0.0 units on scale | Standard Deviation 4.16 |
| Lemborexant 5 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Change at Days 2/3 | -12.1 units on scale | Standard Deviation 46.94 |
| Lemborexant 5 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Baseline | 90.6 units on scale | Standard Deviation 6 |
| Lemborexant 5 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Change at Days2/3 | -1.0 units on scale | Standard Deviation 4.48 |
| Lemborexant 5 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Baseline | 350.0 units on scale | Standard Deviation 65.3 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Baseline | 91.0 units on scale | Standard Deviation 5.15 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Change at Days 2/3 | 1.4 units on scale | Standard Deviation 44.21 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Change at Days2/3 | 0.2 units on scale | Standard Deviation 4.95 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Baseline | 345.7 units on scale | Standard Deviation 67.6 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Change at Days2/3 | -0.7 units on scale | Standard Deviation 3.92 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Change at Days 2/3 | -2.8 units on scale | Standard Deviation 44.11 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | QOM: Baseline | 340.7 units on scale | Standard Deviation 72.75 |
| Lemborexant 10 mg | Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3 | COA: Baseline | 91.3 units on scale | Standard Deviation 4.15 |
Comparison: QOM: Placebo, Lemborexant 5 mgp-value: =0.993695% CI: [-8.16, 8.09]MMRM
Comparison: QOM: Placebo, Lemborexant 10 mgp-value: =0.159595% CI: [-14, 2.3]MMRM
Comparison: QOM: Zolpidem ER, Lemborexant 5 mgp-value: =0.001195% CI: [5.09, 20.38]MMRM
Comparison: QOM: Zolpidem ER, Lemborexant 10 mgp-value: =0.077495% CI: [-0.76, 14.6]MMRM
Comparison: COA: Placebo, Lemborexant 5 mgp-value: =0.372695% CI: [-0.42, 1.12]MMRM
Comparison: COA: Placebo, Lemborexant 10 mgp-value: =0.257995% CI: [-1.22, 0.33]MMRM
Comparison: COA: Zolpidem ER, Lemborexant 5 mgp-value: =0.000295% CI: [0.66, 2.11]MMRM
Comparison: COA: Zolpidem ER, Lemborexant 10 mgp-value: =0.11295% CI: [-0.14, 1.32]MMRM
Other Pre-specified
Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
SE is defined as percentage of time spent in bed asleep, calculated as TST divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 1 and 2 were reported.
Time frame: Baseline, Days 1/2
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | SE: Baseline | 68.89 Percentage of time in bed asleep | Standard Deviation 9.639 |
| Placebo | Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | SE: Change at Days 1/2 | 4.22 Percentage of time in bed asleep | Standard Deviation 9.033 |
| Lemborexant 5 mg | Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | SE: Baseline | 68.36 Percentage of time in bed asleep | Standard Deviation 11.268 |
| Lemborexant 5 mg | Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | SE: Change at Days 1/2 | 13.60 Percentage of time in bed asleep | Standard Deviation 9.725 |
| Lemborexant 10 mg | Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | SE: Baseline | 67.85 Percentage of time in bed asleep | Standard Deviation 10.849 |
| Lemborexant 10 mg | Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2 | SE: Change at Days 1/2 | 16.48 Percentage of time in bed asleep | Standard Deviation 9.623 |
Comparison: SE: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [10.3, 12.9]MMRM
Comparison: SE: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [7.7, 10.31]MMRM
Other Pre-specified
Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time frame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Change at 1st 7 nights: With DHR | 6.73 % of subjective time in bed asleep | Standard Deviation 10.93 |
| Placebo | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Baseline: With DHR | 56.08 % of subjective time in bed asleep | Standard Deviation 17.343 |
| Placebo | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Change at last 7 nights: With DHR | 8.35 % of subjective time in bed asleep | Standard Deviation 13.273 |
| Lemborexant 5 mg | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Change at 1st 7 nights: With DHR | 10.56 % of subjective time in bed asleep | Standard Deviation 12.296 |
| Lemborexant 5 mg | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Baseline: With DHR | 56.05 % of subjective time in bed asleep | Standard Deviation 17.094 |
| Lemborexant 5 mg | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Change at last 7 nights: With DHR | 12.92 % of subjective time in bed asleep | Standard Deviation 13.884 |
| Lemborexant 10 mg | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Baseline: With DHR | 54.31 % of subjective time in bed asleep | Standard Deviation 18.318 |
| Lemborexant 10 mg | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Change at last 7 nights: With DHR | 16.12 % of subjective time in bed asleep | Standard Deviation 16.3 |
| Lemborexant 10 mg | Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSE: Change at 1st 7 nights: With DHR | 13.97 % of subjective time in bed asleep | Standard Deviation 14.188 |
Comparison: sSE, First 7 nights: Placebo, Lemborexant 5 mgp-value: =0.000895% CI: [1.56, 5.97]MMRM
Comparison: sSE, First 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [4.64, 9.04]MMRM
Comparison: sSE, Last 7 nights: Placebo, Lemborexant 5 mgp-value: =0.000595% CI: [2.02, 7.19]MMRM
Comparison: sSE, Last 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [4.6, 9.77]MMRM
Other Pre-specified
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time frame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Baseline: With DHR | 170.89 minutes | Standard Deviation 80.676 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Change at last 7 nights: With DHR | 38.98 minutes | Standard Deviation 66.174 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Change at last 7 nights: With DHR | -36.01 minutes | Standard Deviation 57.584 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Change at 1st 7 nights: With DHR | -27.92 minutes | Standard Deviation 45.201 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Baseline: With DHR | 55.90 minutes | Standard Deviation 37.389 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Change at 1st 7 nights: With DHR | 30.86 minutes | Standard Deviation 57.437 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Change at last 7 nights: With DHR | -8.10 minutes | Standard Deviation 27.447 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Change at 1st 7 nights :With DHR | -6.83 minutes | Standard Deviation 23.04 |
| Placebo | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Baseline: With DHR | 276.23 minutes | Standard Deviation 87.649 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Change at 1st 7 nights: With DHR | -39.33 minutes | Standard Deviation 55.022 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Baseline: With DHR | 65.79 minutes | Standard Deviation 43.53 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Change at 1st 7 nights :With DHR | -22.54 minutes | Standard Deviation 32.812 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Change at last 7 nights: With DHR | -25.20 minutes | Standard Deviation 34.854 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Baseline: With DHR | 166.76 minutes | Standard Deviation 82.047 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Change at last 7 nights: With DHR | -44.51 minutes | Standard Deviation 58.09 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Baseline: With DHR | 275.74 minutes | Standard Deviation 83.65 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Change at 1st 7 nights: With DHR | 50.30 minutes | Standard Deviation 60.065 |
| Lemborexant 5 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Change at last 7 nights: With DHR | 62.41 minutes | Standard Deviation 68.555 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Change at last 7 nights: With DHR | -24.79 minutes | Standard Deviation 34.068 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Baseline: With DHR | 60.88 minutes | Standard Deviation 42.514 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Baseline: With DHR | 266.10 minutes | Standard Deviation 92.164 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sSOL: Change at 1st 7 nights :With DHR | -21.88 minutes | Standard Deviation 29.269 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Change at last 7 nights: With DHR | 79.95 minutes | Standard Deviation 81.211 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Change at 1st 7 nights: With DHR | -55.06 minutes | Standard Deviation 66.696 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Baseline: With DHR | 175.35 minutes | Standard Deviation 83.453 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sTST: Change at 1st 7 nights: With DHR | 67.80 minutes | Standard Deviation 71.134 |
| Lemborexant 10 mg | Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo | sWASO: Change at last 7 nights: With DHR | -57.96 minutes | Standard Deviation 72.791 |
Comparison: sSOL, First 7 nights: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [0.745, 0.891]MMRM
Comparison: sSOL, First 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [0.689, 0.823]MMRM
Comparison: sSOL, Last 7 nights: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [0.671, 0.837]MMRM
Comparison: sSOL, Last 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [0.618, 0.769]MMRM
Comparison: sWASO, First 7 nights: Placebo, Lemborexant 5 mgp-value: =0.009395% CI: [-21.76, -3.06]MMRM
Comparison: sWASO, First 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [-35.68, -16.99]MMRM
Comparison: sWASO, Last 7 nights: Placebo, Lemborexant 5 mgp-value: =0.039695% CI: [-22.42, -0.55]MMRM
Comparison: sWASO, Last 7 nights: Placebo, Lemborexant 10 mgp-value: =0.000295% CI: [-31.51, -9.63]MMRM
Comparison: sTST, First 7 nights: Placebo, Lemborexant 5 mgp-value: =0.000795% CI: [8.03, 30.08]MMRM
Comparison: sTST, First 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [23.5, 45.52]MMRM
Comparison: sTST, Last 7 nights: Placebo, Lemborexant 5 mgp-value: =0.000395% CI: [10.68, 36.45]MMRM
Comparison: sTST, Last 7 nights: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [24.94, 50.71]MMRM
Other Pre-specified
Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
WASO2H is defined as the time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST is defined as the amount of sleep in minutes from sleep onset until terminal awakening. WASO and TST were measured by PSG. Change from baseline to average WASO and TST on Day 29 and 30 were reported.
Time frame: Baseline, Days 29/30
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | WASO2H: Baseline | 74.44 minutes | Standard Deviation 30.109 |
| Placebo | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | WASO2H: Days 29 /30 | -8.92 minutes | Standard Deviation 31.909 |
| Placebo | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | TST: Baseline | 330.67 minutes | Standard Deviation 46.268 |
| Placebo | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | TST: Days 29/30 | 25.65 minutes | Standard Deviation 47.587 |
| Lemborexant 5 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | TST: Days 29/30 | 61.99 minutes | Standard Deviation 46.817 |
| Lemborexant 5 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | WASO2H: Baseline | 76.60 minutes | Standard Deviation 32.903 |
| Lemborexant 5 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | TST: Baseline | 328.00 minutes | Standard Deviation 54.224 |
| Lemborexant 5 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | WASO2H: Days 29 /30 | -27.19 minutes | Standard Deviation 33.047 |
| Lemborexant 10 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | TST: Days 29/30 | 67.86 minutes | Standard Deviation 52.117 |
| Lemborexant 10 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | WASO2H: Days 29 /30 | -28.84 minutes | Standard Deviation 33.138 |
| Lemborexant 10 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | TST: Baseline | 325.07 minutes | Standard Deviation 52.819 |
| Lemborexant 10 mg | Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30 | WASO2H: Baseline | 76.88 minutes | Standard Deviation 32.126 |
Comparison: WASO2H: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [-21.23, -11.6]MMRM
Comparison: WASO2H: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [-22.57, -12.96]MMRM
Comparison: TST: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [26.95, 41.36]MMRM
Comparison: TST: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [31.64, 46.05]MMRM
Other Pre-specified
Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31
The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: severity of sleep onset; sleep maintenance; early morning awakening problems; sleep dissatisfaction; interference of sleep difficulties with daytime functioning; noticeability of the sleep problems by others; and distress caused by the sleep difficulties. A 5-point Likert scale was used to rate each item (from 0 = no problem to 4 = very severe problem) yielding a total score from 0 to 28.
Time frame: Baseline and Day 31
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 11.21 score on scale | Standard Deviation 2.436 |
| Placebo | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -3.88 score on scale | Standard Deviation 3.559 |
| Lemborexant 5 mg | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -5.24 score on scale | Standard Deviation 3.764 |
| Lemborexant 5 mg | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 11.06 score on scale | Standard Deviation 2.508 |
| Lemborexant 10 mg | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 10.91 score on scale | Standard Deviation 2.419 |
| Lemborexant 10 mg | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -4.83 score on scale | Standard Deviation 3.593 |
| Lemborexant 10 mg | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Baseline | 10.84 score on scale | Standard Deviation 2.334 |
| Lemborexant 10 mg | Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31 | Change at Day 31 | -4.77 score on scale | Standard Deviation 3.735 |
Comparison: Placebo, Lemborexant 5 mgp-value: =0.000695% CI: [-1.73, -0.47]ANCOVA
Comparison: Placebo, Lemborexant 10 mgp-value: =0.000795% CI: [-1.71, -0.46]ANCOVA
Comparison: Zolpidem ER, Lemborexant 5 mgp-value: =0.295195% CI: [-0.28, 0.91]ANCOVA
Comparison: Zolpidem ER, Lemborexant 10 mgp-value: =0.274495% CI: [-0.26, 0.92]ANCOVA
Other Pre-specified
Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time frame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Change at 1st 7 nights: With DHR | 11.96 % of subjective time in bed asleep | Standard Deviation 12.526 |
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Baseline: With DHR | 55.49 % of subjective time in bed asleep | Standard Deviation 15.802 |
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Change at last 7 nights: With DHR | 14.83 % of subjective time in bed asleep | Standard Deviation 15.011 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Change at 1st 7 nights: With DHR | 10.56 % of subjective time in bed asleep | Standard Deviation 12.296 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Baseline: With DHR | 56.05 % of subjective time in bed asleep | Standard Deviation 17.094 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Change at last 7 nights: With DHR | 12.92 % of subjective time in bed asleep | Standard Deviation 13.884 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Baseline: With DHR | 54.31 % of subjective time in bed asleep | Standard Deviation 18.318 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Change at last 7 nights: With DHR | 16.12 % of subjective time in bed asleep | Standard Deviation 16.3 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSE: Change at 1st 7 nights: With DHR | 13.97 % of subjective time in bed asleep | Standard Deviation 14.188 |
Comparison: sSE, First 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.196395% CI: [-3.46, 0.71]MMRM
Comparison: sSE, First 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.109395% CI: [-0.38, 3.78]MMRM
Comparison: sSE, Last 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.219695% CI: [-3.98, 0.92]MMRM
Comparison: sSE, Last 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.401395% CI: [-1.4, 3.49]MMRM
Other Pre-specified
Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with diary handling rules (DHR) on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time frame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: Baseline: With DHR | 60.54 minutes | Standard Deviation 36.35 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Change at last 7 nights: With DHR | -63.52 minutes | Standard Deviation 64.161 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: last 7 nights: With DHR | -17.04 minutes | Standard Deviation 30.683 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: 1st 7 nights: With DHR | -16.23 minutes | Standard Deviation 29.531 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Baseline: With DHR | 273.07 minutes | Standard Deviation 81.207 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Change at 1st 7 nights: With DHR | -48.91 minutes | Standard Deviation 51.761 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Change at last 7 nights: With DHR | 71.01 minutes | Standard Deviation 76.574 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Change at 1st 7 nights: With DHR | 56.99 minutes | Standard Deviation 62.88 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Baseline: With DHR | 173.06 minutes | Standard Deviation 77.212 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: 1st 7 nights: With DHR | -22.54 minutes | Standard Deviation 32.812 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Baseline: With DHR | 275.74 minutes | Standard Deviation 83.65 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Change at 1st 7 nights: With DHR | 50.30 minutes | Standard Deviation 60.065 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Change at last 7 nights: With DHR | 62.41 minutes | Standard Deviation 68.555 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: Baseline: With DHR | 65.79 minutes | Standard Deviation 43.53 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: last 7 nights: With DHR | -25.20 minutes | Standard Deviation 34.854 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Baseline: With DHR | 166.76 minutes | Standard Deviation 82.047 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Change at 1st 7 nights: With DHR | -39.33 minutes | Standard Deviation 55.022 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Change at last 7 nights: With DHR | -44.51 minutes | Standard Deviation 58.09 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Change at last 7 nights: With DHR | 79.95 minutes | Standard Deviation 81.211 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Baseline: With DHR | 266.10 minutes | Standard Deviation 92.164 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Baseline: With DHR | 175.35 minutes | Standard Deviation 83.453 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sTST: Change at 1st 7 nights: With DHR | 67.80 minutes | Standard Deviation 71.134 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Change at last 7 nights: With DHR | -57.96 minutes | Standard Deviation 72.791 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: 1st 7 nights: With DHR | -21.88 minutes | Standard Deviation 29.269 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: Baseline: With DHR | 60.88 minutes | Standard Deviation 42.514 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sWASO: Change at 1st 7 nights: With DHR | -55.06 minutes | Standard Deviation 66.696 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER | sSOL: last 7 nights: With DHR | -24.79 minutes | Standard Deviation 34.068 |
Comparison: sSOL, First 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.012295% CI: [0.825, 0.977]MMRM
Comparison: sSOL, First 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [0.763, 0.902]MMRM
Comparison: sSOL, Last 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.017695% CI: [0.796, 0.978]MMRM
Comparison: sSOL, Last 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [0.732, 0.899]MMRM
Comparison: sWASO, First 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.070695% CI: [-0.68, 16.91]MMRM
Comparison: sWASO, First 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.194995% CI: [-14.61, 2.98]MMRM
Comparison: sWASO, Last 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.005995% CI: [4.16, 24.73]MMRM
Comparison: sWASO, Last 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.306495% CI: [-4.92, 15.65]MMRM
Comparison: sTST, First 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.217495% CI: [-17.02, 3.88]MMRM
Comparison: sTST, First 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.094995% CI: [-1.55, 19.31]MMRM
Comparison: sTST, Last 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.271895% CI: [-19.01, 5.36]MMRM
Comparison: sTST, Last 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.231795% CI: [-4.75, 19.61]MMRM
Other Pre-specified
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
Objective sleep onset response: LPS less than or equal to (\<=) 20 minutes (mins) provided baseline LPS was greater than (\>) 30 mins. Subjective sleep onset response: sSOL \<=20 mins provided mean baseline sSOL was \>30 mins. Objective sleep maintenance response: WASO \<=60 minutes provided baseline WASO was \>60 mins and was reduced by \>10 mins compared to baseline. Subjective sleep maintenance response: sWASO \<=60 mins provided mean WASO was \>60 mins and was reduced by \>10 mins compared to baseline. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. Average data for Days 1 and 2, Days 29 and 30, and first and last 7 nights of treatment period was reported.
Time frame: Days 1/2, Days 29/30, first 7 night (approximately Week 1), and Last seven nights (approximately Week 4)
Population: FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 1/2 | 15.4 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 29/30 | 15.9 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: First 7 nights (with DHR) | 2.9 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: Last 7 nights (with DHR) | 7.2 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 1/2 | 16.8 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 29/30 | 22.1 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: First 7 nights (with DHR) | 9.6 percentage of participants |
| Placebo | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: Last 7 nights (with DHR) | 15.4 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 29/30 | 11.4 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 1/2 | 46.0 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: First 7 nights (with DHR) | 16.7 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 29/30 | 34.6 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: Last 7 nights (with DHR) | 23.2 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: Last 7 nights (with DHR) | 8.7 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: First 7 nights (with DHR) | 7.6 percentage of participants |
| Lemborexant 5 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 1/2 | 10.3 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: First 7 nights (with DHR) | 16.9 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: First 7 nights (with DHR) | 9.8 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: Last 7 nights (with DHR) | 16.9 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: Last 7 nights (with DHR) | 23.3 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 1/2 | 51.1 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 29/30 | 44.4 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 1/2 | 15.8 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 29/30 | 20.3 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: Last 7 nights (with DHR) | 23.0 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: Last 7 nights (with DHR) | 14.5 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 29/30 | 22.3 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | LPS: Days 1/2 | 17.8 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sWASO: First 7 nights (with DHR) | 20.4 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 1/2 | 64.3 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | sSOL: First 7 nights (with DHR) | 10.4 percentage of participants |
| Lemborexant 10 mg | Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response | WASO: Days 29/30 | 46.1 percentage of participants |
Comparison: LPS, Days 1/2: Placebo, Lemborexant 5 mgp-value: =0.902895% CI: [-6.22, 7.04]Cochran-Mantel-Haenszel
Comparison: LPS, Days 1/2: Placebo, Lemborexant 10 mgp-value: =0.469995% CI: [-4.2, 9.18]Cochran-Mantel-Haenszel
Comparison: LPS, Days 1/2: Zolpidem ER, Lemborexant 5 mgp-value: =0.056695% CI: [-0.14, 11.31]Cochran-Mantel-Haenszel
Comparison: LPS, Days 1/2: Zolpidem ER, Lemborexant 10 mgp-value: =0.012295% CI: [1.71, 13.44]Cochran-Mantel-Haenszel
Comparison: LPS, Days 29/30: Placebo, Lemborexant 5 mgp-value: =0.217695% CI: [-2.5, 11.34]Cochran-Mantel-Haenszel
Comparison: LPS, Days 29/30: Placebo, Lemborexant 10 mgp-value: =0.077395% CI: [-0.55, 13.49]Cochran-Mantel-Haenszel
Comparison: LPS, Days 29/30: Zolpidem ER, Lemborexant 5 mgp-value: =0.005495% CI: [2.68, 15.02]Cochran-Mantel-Haenszel
Comparison: LPS, Days 29/30: Zolpidem ER, Lemborexant 10 mgp-value: =0.000895% CI: [4.61, 17.17]Cochran-Mantel-Haenszel
Comparison: sSOL, First 7 nights: Placebo, Lemborexant 5 mgp-value: =0.00395% CI: [2.66, 11.14]Cochran-Mantel-Haenszel
Comparison: sSOL, First 7 nights: Placebo, Lemborexant 10 mgp-value: =0.001695% CI: [3.19, 11.81]Cochran-Mantel-Haenszel
Comparison: sSOL, First 7 nights: Zolpidem, Lemborexant 5 mgp-value: =0.364395% CI: [-2.56, 7.01]Cochran-Mantel-Haenszel
Comparison: sSOL, First 7 nights: Zolpidem, Lemborexant 10 mgp-value: =0.255395% CI: [-2.02, 7.66]Cochran-Mantel-Haenszel
Comparison: sSOL, Last 7 nights: Placebo, Lemborexant 5 mgp-value: =0.001695% CI: [3.98, 15.4]Cochran-Mantel-Haenszel
Comparison: sSOL, Last 7 nights: Placebo, Lemborexant 10 mgp-value: =0.012895% CI: [1.8, 12.79]Cochran-Mantel-Haenszel
Comparison: sSOL, Last 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.005195% CI: [2.51, 13.81]Cochran-Mantel-Haenszel
Comparison: sSOL, Last 7nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.038995% CI: [0.34, 11.18]Cochran-Mantel-Haenszel
Comparison: WASO, Days 1/2: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [26.46, 42.06]Cochran-Mantel-Haenszel
Comparison: WASO, Days 1/2: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [40.02, 55.13]Cochran-Mantel-Haenszel
Comparison: WASO, Days 1/2: Zolpidem ER, Lemborexant 5 mgp-value: =0.253495% CI: [-3.49, 13.28]Cochran-Mantel-Haenszel
Comparison: WASO: Days 1/2: Zolpidem ER, Lemborexant 10 mgp-value: <0.000195% CI: [10.1, 26.4]Cochran-Mantel-Haenszel
Comparison: WASO, Days 29/30: Placebo, Lemborexant 5 mgp-value: <0.000195% CI: [14.06, 30.35]Cochran-Mantel-Haenszel
Comparison: WASO, Days 29/30: Placebo, Lemborexant 10 mgp-value: <0.000195% CI: [16.16, 32.1]Cochran-Mantel-Haenszel
Comparison: WASO, Days 29/30: Zolpidem ER, Lemborexant 5 mgp-value: =0.02395% CI: [1.36, 17.81]Cochran-Mantel-Haenszel
Comparison: WASO, Days 29/30: Zolpidem ER, Lemborexant 10 mgp-value: =0.005895% CI: [3.38, 19.48]Cochran-Mantel-Haenszel
Comparison: sWASO, First 7 nights: Placebo, Lemborexant 5p-value: =0.022295% CI: [1.27, 13.33]Cochran-Mantel-Haenszel
Comparison: sWASO, First 7 nights: Placebo, Lemborexant 10 mgp-value: =0.001395% CI: [4.57, 17.11]Cochran-Mantel-Haenszel
Comparison: sWASO, First 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.949595% CI: [-6.17, 6.58]Cochran-Mantel-Haenszel
Comparison: sWASO: First 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.270895% CI: [-2.88, 10.32]Cochran-Mantel-Haenszel
Comparison: sWASO, Last 7 nights: Placebo, Lemborexant 5 mgp-value: =0.032295% CI: [0.86, 14.96]Cochran-Mantel-Haenszel
Comparison: sWASO, Last 7 nights: Placebo, Lemborexant 10 mgp-value: =0.036395% CI: [0.68, 14.71]Cochran-Mantel-Haenszel
Comparison: sWASO, Last 7 nights: Zolpidem ER, Lemborexant 5 mgp-value: =0.988595% CI: [-7.14, 7.24]Cochran-Mantel-Haenszel
Comparison: sWASO, Last 7 nights: Zolpidem ER, Lemborexant 10 mgp-value: =0.965195% CI: [-7.31, 6.99]Cochran-Mantel-Haenszel