Insomnia Disorder
Conditions
Keywords
insomnia
Brief summary
The key objectives of this study are to determine, using sleep diaries, whether lemborexant at the doses 5 milligrams (mg) and 10 mg is superior to placebo on subjective sleep onset, subjective sleep efficiency, and subjective sleep maintenance in participants with insomnia disorder.
Detailed description
This is a long-term (approximately 1 year), multicenter, randomized, controlled, double-blind, parallel group study of two doses of lemborexant and placebo in approximately 900 male or female participants with insomnia disorder. Approximately 40% of participants will be age 65 years or older. The study will last a maximum of 60 weeks, and will include a Screening Period, an approximately 54-week Treatment Period (during which study medication will be administered), and a 2-week Follow-up Period. All participants will receive lemborexant for at least 6 months and will receive placebo at some point during the study. Participants will not know which medication they receive (lemborexant or placebo) until the study has been completed, and will not know the timings at which the medication will change.
Interventions
DRUGlemborexant
DRUGPlacebo
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age 18 years or older at the time of informed consent * Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria for Insomnia Disorder, as follows: * Complains of dissatisfaction with nighttime sleep in the form of difficulty getting to sleep, difficulty staying asleep, and/or awakening earlier in the morning than desired despite adequate opportunity for sleep * Frequency of complaint ≥3 times per week * Duration of complaint ≥3 months * Associated with complaint of daytime impairment * History of (Subjective Sleep Onset Latency) sSOL ≥30 minutes on at least 3 nights per week in the previous 4 weeks and/or subjective Wake after Sleep Onset (sWASO) ≥60 minutes on at least 3 nights per week in the previous 4 weeks * History of regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours * Regular bedtime, between 21:00 and 01:00 and regular wake time, the time the participant gets out of bed for the day, between 05:00 and 10:00 * Insomnia Severity Index (ISI) score ≥15 * Confirmation of current insomnia symptoms as determined from the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL ≥30 minutes on at least 3 of the 7 nights and/or sWASO ≥60 minutes on at least 3 of the 7 nights * Confirmation of time spent in bed, as determined from on the Sleep Diary completed on 7 mornings between the first and second screening visit, such that there are not more than 2 nights with duration of time spent in bed 7 hours and 10 hours * Confirmation of regular bedtimes and wake times such that the participant has a regular time spent in bed, either sleeping or trying to sleep, between 7 and 10 hours for the final 7 nights of the before visit 3. * Confirmation of regular bedtime between 21:00 and 01:00 and time of getting out of bed for the day between 05:00 and 10:00 for the final 7 nights of the before visit 3. * Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night * Willing to not start a behavioral or other treatment program for insomnia during the participants participation in the study
Exclusion criteria
* A current diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia. * STOPBang score greater than or equal to (\>=) 5 * International Restless Legs Scale (IRLS) score \>=16 * Epworth Sleepiness Scale (ESS) score \>15 * 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 * Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior, eg, making phone calls, or preparing and eating food while asleep * For participants who underwent polysomnography (PSG) within the previous year: * Age 18 to 64 years: Apnea Hypopnea Index ≥10, or Periodic Limb Movements with Arousal Index ≥10 * Age ≥65 years: Apnea Hypopnea Index \>15, or Periodic Limb Movements with Arousal Index \>15 * Beck Depression Inventory - II (BDI II) score \>19 at Screening * Beck Anxiety Inventory (BAI) score \>15 at Screening * Habitually naps more than 3 times per week * Females who are breastfeeding or pregnant at Screening or Study Baseline * Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.) * 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 * History of drug or alcohol dependency or abuse within approximately the previous 2 years * 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 * A prolonged QT/QT interval corrected by Fridericia's formula (QTcF \>450 ms) as demonstrated by a repeated electro cardiogram(ECG) at Screening (repeated only if initial ECG indicates a QTcF interval \>450 ms) * Current evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, neurological \[including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation\], or psychiatric disease or malignancy other than 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 * Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night * Scheduled for major surgery during the study * Used any prohibited prescription or over-the-counter concomitant medications within 1 week before the first dose of study medication * Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks before Screening * 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 * Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Study Baseline * Previously participated in any clinical trial of lemborexant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Baseline and Month 6 | sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6 | sSE was defined as percentage of subjective total sleep time (sTST) divided by subjective time spent in bed, calculated as the interval from the time the participant reported attempting to sleep until the time participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. |
| Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6 | sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. |
| Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6 | sTST was defined as minutes of sleep from sleep onset to time stopped trying to sleep for the night. |
| Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Month 6 | Sleep onset responder was defined as follows: sSOL at study Baseline was greater than or equal to (\>=) 30 minutes and mean sSOL at 6 months was less than or equal to (\<=) 20 minutes. Sleep maintenance responder was defined as follows: sWASO at study Baseline was \>=60 minutes and mean sWASO at 6 months was \<=60 minutes and showed a reduction of greater than (\>)10 minutes compared to Study Baseline. |
| Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 | Month 12 | Sleep onset responder was defined as follows: sSOL at study Baseline was \>=30 minutes and mean sSOL at 6 months was \<=20 minutes. Sleep maintenance responder was defined as follows: sWASO at study Baseline was \>=60 minutes and mean sWASO at 6 months was \<=60 minutes and showed a reduction of \> 10 minutes compared to study Baseline. |
| Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Baseline, Months 1, 3, and 6 | The ISI is a 4-7 item, self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: 1. severity of sleep onset; 2. sleep maintenance; 3. early morning awakening problems; 4. sleep dissatisfaction; 5. interference of sleep difficulties with daytime functioning; 6. noticeability of the sleep problems by others; and 7. 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). Daytime functioning score (sum of items 4 to 7) were analyzed. Higher score indicated severe insomnia problem. The total score range for sum of items is 0-16. |
| Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Baseline, Months 1, 3 and 6 | The FSS is a self-reported scale on which participants were instructed to choose a number from 1 to 7 that indicated their degree of agreement with 9 statements about their fatigue where 1 indicates strongly disagree and 7, strongly agree. The FSS total score was the sum of all responses to the 9 questions. Higher total scores and average item scores indicated greater fatigue. Total score range is 9 to 63. |
| Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline, (mean of 7 nights [approximately Week 1]) in placebo-controlled period, Month 1, 3, 6 | The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: How sleepy/alert do you feel this morning? Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome. |
| Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period) | Baseline, First 7 nights (approximately Week 1) in active treatment period | — |
| Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Screening, First and second 7 mornings in follow-up period (Week 52 to 54) | The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: How sleepy/alert do you feel this morning? Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome. |
| Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Baseline, (mean of 7 nights [approximately Week 1]), Months 1 and 3 | sSOL was defined as estimated minutes from time attempted to sleep to sleep onset. |
| Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | First 3 nights, first and Last 7 nights of the follow up period (Week 52 to 54) | Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. |
| Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54) | Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. |
| Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54) | Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. |
| Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | First 3 nights, First and Last 7 nights of the follow up period (Week 52 to 54) | Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. |
| Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | Baseline, Month 1, 3, 6, 9, 12 | sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At each month beyond Month 1, the change from Baseline was compared to either the lower bound of the 95% CI (for sTST) or the upper bound of the 95% CI (for sSOL and sWASO) at Month 1. Persistence of efficacy was defined as present if the mean change from Baseline at Month 6 was above the lower bound of the 95% CI at Month 1 for sTST and below the upper bound of the 95% CI at Month 1 for sSOL and sWASO. |
| Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Baseline, Months 1, 3, 6, 9, and 12 | sSE was defined as percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At each month beyond Month 1, the change from Baseline was compared to the lower bound of the 95% CI at Month 1. Persistence of efficacy was defined as present if the mean change from Baseline at Month 6 was above the lower bound of the 95% CI at Month 1 for sSE. |
| Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | Baseline, Month 7, 9, 12 | sSOL is defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO: sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At each month beyond Month 7, the change from Baseline was compared to either the lower bound of the 95% CI for sTST or the upper bound of the 95% CI (for sSOL and sWASO) at Month 7. Persistence of effect was defined as present if the mean change from Baseline at Month 12 was above the lower bound of the 95% CI at Month 7 for sTST and below the upper bound of the 95% CI at Month 7 for sSOL and sWASO. |
| Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Baseline, Month 7, 9, 12 | sSE: percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the subject got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At each month beyond Month 7, the change from Baseline was compared to the lower bound of the 95% CI for sSE at Month 7. Persistence of effect was defined as present if the mean change from Baseline at Month 12 was above the lower bound of the 95% CI at Month 7 for sSE. |
| Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | Baseline, Month 1, 3, 6 | sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO: sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At 3 and 6 months of exposure, the change from Baseline was compared to either the lower bound of the 95% CI for sTST or the upper bound of the 95% CI (for sSOL and sWASO) at 1 month of exposure. Persistence of effect was defined as present if the mean change from Baseline at 6 months of exposure was above the lower bound of the 95% CI at 1 month of exposure for sTST and below the upper bound of the 95% CI at 1 month of exposure for sSOL and sWASO. |
| Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Baseline, Month 1, 3, 6 | sSE was defined as percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At 3 and 6 months of exposure, the change from Baseline was compared to the lower bound of the 95% CI for sSE at 1 month of exposure. Persistence of effect was defined as present if the mean change from Baseline at 6 months of exposure was above the lower bound of the 95% CI at 1 month of exposure for sSE. |
| Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Baseline, Months 1, 3, 6, 9 and 12 | The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: How sleepy/alert do you feel this morning? Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome. |
Countries
Canada, Finland, Germany, Italy, Japan, Mexico, New Zealand, Poland, Romania, South Korea, Spain, United States
Participant flow
Recruitment details
Participants took part in the study at 119 investigative sites in Japan, Korea, Finland, Germany, Italy, New Zealand, Poland, Romania, Spain, Canada, Mexico, and the United States from 15 November 2016 to 08 January 2019.
Pre-assignment details
A total of 2059 participants were screened, of which 1088 were screen failures and 971 participants were randomized to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12. | 318 |
| Lemborexant 5 mg Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | 316 |
| Lemborexant 10 mg Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | 315 |
| Total | 949 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Active Treatment Period (6 Months) | Adverse Event | 0 | 6 | 5 |
| Active Treatment Period (6 Months) | Inadequate therapeutic effect | 0 | 6 | 2 |
| Active Treatment Period (6 Months) | Lost to Follow-up | 0 | 4 | 6 |
| Active Treatment Period (6 Months) | Not treated | 0 | 0 | 1 |
| Active Treatment Period (6 Months) | Other than specified | 0 | 6 | 2 |
| Active Treatment Period (6 Months) | Subject choice | 0 | 10 | 7 |
| Active Treatment Period (6 Months) | Withdrawal of consent | 0 | 6 | 8 |
| Placebo-Controlled Treatment (6 Months) | Adverse Event | 8 | 9 | 16 |
| Placebo-Controlled Treatment (6 Months) | Inadequate therapeutic effect | 17 | 12 | 11 |
| Placebo-Controlled Treatment (6 Months) | Lost to Follow-up | 7 | 7 | 6 |
| Placebo-Controlled Treatment (6 Months) | Not treated | 4 | 4 | 4 |
| Placebo-Controlled Treatment (6 Months) | Other than specified | 0 | 14 | 13 |
| Placebo-Controlled Treatment (6 Months) | Subject choice | 15 | 12 | 17 |
| Placebo-Controlled Treatment (6 Months) | Withdrawal of consent | 13 | 11 | 21 |
Baseline characteristics
| Characteristic | Lemborexant 10 mg | Lemborexant 5 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 13.68 | 54.2 years STANDARD_DEVIATION 13.74 | 54.5 years STANDARD_DEVIATION 14.01 | 54.5 years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 19 Participants | 34 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 296 Participants | 297 Participants | 284 Participants | 877 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 26 Participants | 27 Participants | 23 Participants | 76 Participants |
| Race/Ethnicity, Customized Chinese | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Japanese | 54 Participants | 53 Participants | 54 Participants | 161 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized Other Asian | 3 Participants | 5 Participants | 5 Participants | 13 Participants |
| Race/Ethnicity, Customized White | 225 Participants | 222 Participants | 232 Participants | 679 Participants |
| Sex: Female, Male Female | 222 Participants | 209 Participants | 216 Participants | 647 Participants |
| Sex: Female, Male Male | 93 Participants | 107 Participants | 102 Participants | 302 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 319 | 0 / 447 | 0 / 437 |
| other Total, other adverse events | 75 / 319 | 129 / 447 | 140 / 437 |
| serious Total, serious adverse events | 5 / 319 | 18 / 447 | 16 / 437 |
Outcome results
Primary
Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6
sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset.
Time frame: Baseline and Month 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Baseline | 64.03 minutes | Standard Deviation 45.209 |
| Placebo | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Change at Month 6 | -16.57 minutes | Standard Deviation 35.313 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Baseline | 62.19 minutes | Standard Deviation 45.674 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Change at Month 6 | -29.39 minutes | Standard Deviation 33.261 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Baseline | 64.97 minutes | Standard Deviation 44.02 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 | Change at Month 6 | -32.49 minutes | Standard Deviation 35.962 |
Comparison: Analysis was based on mixed effect model repeated measurement analysis (MMRM) model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (missing not at random/complete case missing value \[MNAR/CCMV\]).p-value: <0.000195% CI: [0.636, 0.843]Mixed Models Analysis
Comparison: Analysis was based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.607, 0.81]Mixed Models Analysis
Secondary
Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6
The FSS is a self-reported scale on which participants were instructed to choose a number from 1 to 7 that indicated their degree of agreement with 9 statements about their fatigue where 1 indicates strongly disagree and 7, strongly agree. The FSS total score was the sum of all responses to the 9 questions. Higher total scores and average item scores indicated greater fatigue. Total score range is 9 to 63.
Time frame: Baseline, Months 1, 3 and 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 3 | -4.3 score on a scale | Standard Deviation 11.37 |
| Placebo | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 1 | -3.9 score on a scale | Standard Deviation 11.62 |
| Placebo | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Baseline | 35.2 score on a scale | Standard Deviation 13.55 |
| Placebo | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 6 | -6.3 score on a scale | Standard Deviation 12.07 |
| Lemborexant 5 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 1 | -6.6 score on a scale | Standard Deviation 11.83 |
| Lemborexant 5 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Baseline | 37.4 score on a scale | Standard Deviation 12.74 |
| Lemborexant 5 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 6 | -10.1 score on a scale | Standard Deviation 13.56 |
| Lemborexant 5 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 3 | -7.7 score on a scale | Standard Deviation 12.97 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Baseline | 36.0 score on a scale | Standard Deviation 13.01 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 6 | -8.9 score on a scale | Standard Deviation 14.91 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 3 | -7.9 score on a scale | Standard Deviation 13.56 |
| Lemborexant 10 mg | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 | Change at Month 1 | -6.4 score on a scale | Standard Deviation 13.68 |
Comparison: Month 1 (Statistical analysis 1): Based on MMRM model with factors for age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effects, and study baseline FSS score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.06795% CI: [-3.44, 0.12]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 2): Based on MMRM model with factors for age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effects, and study baseline FSS score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.025795% CI: [-3.83, -0.25]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 3): Based on MMRM model with factors for age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effects, and study baseline FSS score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.020695% CI: [-4.02, -0.34]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 4): Based on MMRM model with factors for age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effects, and study baseline FSS score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.001495% CI: [-4.91, -1.18]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 5): Based on MMRM model with factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and study baseline FSS score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.013495% CI: [-4.48, -0.52]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 6): Based on MMRM model with factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and study baseline FSS score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.012895% CI: [-4.57, -0.54]Mixed Models Analysis
Secondary
Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6
The ISI is a 4-7 item, self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: 1. severity of sleep onset; 2. sleep maintenance; 3. early morning awakening problems; 4. sleep dissatisfaction; 5. interference of sleep difficulties with daytime functioning; 6. noticeability of the sleep problems by others; and 7. 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). Daytime functioning score (sum of items 4 to 7) were analyzed. Higher score indicated severe insomnia problem. The total score range for sum of items is 0-16.
Time frame: Baseline, Months 1, 3, and 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 6 | -4.3 score on a scale | Standard Deviation 3.66 |
| Placebo | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 1 | -3.1 score on a scale | Standard Deviation 3.41 |
| Placebo | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Baseline | 11.0 score on a scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 3 | -3.7 score on a scale | Standard Deviation 3.55 |
| Lemborexant 5 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 1 | -4.1 score on a scale | Standard Deviation 3.66 |
| Lemborexant 5 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Baseline | 11.4 score on a scale | Standard Deviation 2.02 |
| Lemborexant 5 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 3 | -5.2 score on a scale | Standard Deviation 3.88 |
| Lemborexant 5 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 6 | -6.0 score on a scale | Standard Deviation 3.76 |
| Lemborexant 10 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Baseline | 11.0 score on a scale | Standard Deviation 2.15 |
| Lemborexant 10 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 6 | -5.7 score on a scale | Standard Deviation 4 |
| Lemborexant 10 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 3 | -5.2 score on a scale | Standard Deviation 4.05 |
| Lemborexant 10 mg | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 | Change at Month 1 | -4.2 score on a scale | Standard Deviation 4.01 |
Comparison: Month 1 (Statistical analysis 1): Based on MMRM model with factors for age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effects, and study baseline ISI score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.013795% CI: [-1.27, -0.15]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 2): Based on MMRM model with factors for age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effects, and study baseline ISI score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.001195% CI: [-1.51, -0.38]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 3): Based on MMRM model with factors for age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effects, and study baseline ISI score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.000195% CI: [-1.75, -0.57]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 4): Based on MMRM model with factors for age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effects, and study baseline ISI score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: <0.000195% CI: [-1.96, -0.76]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 5): Based on MMRM model with factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and study baseline ISI score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: <0.000195% CI: [-1.9, -0.71]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 6): Based on MMRM model with factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and study baseline ISI score as a covariate. Missing values are not imputed and assumed to be MAR.p-value: <0.000195% CI: [-1.92, -0.71]Mixed Models Analysis
Secondary
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12
The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: How sleepy/alert do you feel this morning? Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome.
Time frame: Baseline, Months 1, 3, 6, 9 and 12
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Baseline | 4.15 score on a scale | Standard Deviation 1.516 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 1 of exposure | 0.46 score on a scale | Standard Deviation 1.082 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 9 of exposure | 1.00 score on a scale | Standard Deviation 1.512 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 3 of exposure | 0.60 score on a scale | Standard Deviation 1.264 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 6 of exposure | 0.78 score on a scale | Standard Deviation 1.424 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 12 of exposure | 1.11 score on a scale | Standard Deviation 1.499 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 6 of exposure | 0.86 score on a scale | Standard Deviation 1.461 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Baseline | 4.16 score on a scale | Standard Deviation 1.428 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 3 of exposure | 0.70 score on a scale | Standard Deviation 1.356 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 1 of exposure | 0.42 score on a scale | Standard Deviation 1.223 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 12 of exposure | 1.31 score on a scale | Standard Deviation 1.604 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 | Change at Month 9 of exposure | 1.08 score on a scale | Standard Deviation 1.489 |
Secondary
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period)
Time frame: Baseline, First 7 nights (approximately Week 1) in active treatment period
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period) | Change at First 7 nights | 0.36 score on a scale | Standard Deviation 0.964 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period) | Baseline | 4.15 score on a scale | Standard Deviation 1.516 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period) | Baseline | 4.16 score on a scale | Standard Deviation 1.428 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period) | Change at First 7 nights | 0.33 score on a scale | Standard Deviation 1.018 |
Secondary
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: How sleepy/alert do you feel this morning? Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome.
Time frame: Baseline, (mean of 7 nights [approximately Week 1]) in placebo-controlled period, Month 1, 3, 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 3.94 score on a scale | Standard Deviation 1.558 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at First 7 nights | 0.15 score on a scale | Standard Deviation 0.991 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 0.44 score on a scale | Standard Deviation 1.233 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 0.62 score on a scale | Standard Deviation 1.366 |
| Placebo | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 0.79 score on a scale | Standard Deviation 1.392 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 3.93 score on a scale | Standard Deviation 1.349 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 0.74 score on a scale | Standard Deviation 1.325 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at First 7 nights | 0.36 score on a scale | Standard Deviation 0.964 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 0.53 score on a scale | Standard Deviation 1.172 |
| Lemborexant 5 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 0.98 score on a scale | Standard Deviation 1.463 |
| Lemborexant 10 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 0.55 score on a scale | Standard Deviation 1.298 |
| Lemborexant 10 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 3.93 score on a scale | Standard Deviation 1.324 |
| Lemborexant 10 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 1.05 score on a scale | Standard Deviation 1.524 |
| Lemborexant 10 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 0.90 score on a scale | Standard Deviation 1.452 |
| Lemborexant 10 mg | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at First 7 nights | 0.33 score on a scale | Standard Deviation 1.018 |
Comparison: First 7 nights (Statistical analysis): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.006795% CI: [0.057, 0.353]Mixed Models Analysis
Comparison: First 7 nights (Statistical analysis 2): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.023795% CI: [0.023, 0.32]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 3): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.41295% CI: [-0.107, 0.261]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 4): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.434795% CI: [-0.111, 0.258]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 5): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.499295% CI: [-0.141, 0.289]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 6): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.020895% CI: [0.039, 0.471]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 7): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.224895% CI: [-0.089, 0.378]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 8): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline Mean Rating on Morning Sleepiness as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.029895% CI: [0.026, 0.497]Mixed Models Analysis
Secondary
Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3
sSOL was defined as estimated minutes from time attempted to sleep to sleep onset.
Time frame: Baseline, (mean of 7 nights [approximately Week 1]), Months 1 and 3
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at 1st 7 nights | -4.11 minutes | Standard Deviation 27.671 |
| Placebo | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at Month 3 | -13.84 minutes | Standard Deviation 35.277 |
| Placebo | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Baseline | 64.03 minutes | Standard Deviation 45.209 |
| Placebo | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at Month 1 | -11.48 minutes | Standard Deviation 32.726 |
| Lemborexant 5 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at Month 1 | -19.41 minutes | Standard Deviation 32.221 |
| Lemborexant 5 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Baseline | 62.19 minutes | Standard Deviation 45.674 |
| Lemborexant 5 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at Month 3 | -25.08 minutes | Standard Deviation 34.081 |
| Lemborexant 5 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at 1st 7 nights | -16.86 minutes | Standard Deviation 27.784 |
| Lemborexant 10 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at Month 3 | -27.94 minutes | Standard Deviation 39.192 |
| Lemborexant 10 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at 1st 7 nights | -18.89 minutes | Standard Deviation 31.003 |
| Lemborexant 10 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Baseline | 64.97 minutes | Standard Deviation 44.02 |
| Lemborexant 10 mg | Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3 | Change at Month 1 | -24.06 minutes | Standard Deviation 35.234 |
Comparison: First 7 nights after the first dose (Statistical analysis 1): Based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.725, 0.842]Mixed Models Analysis
Comparison: First 7 nights after the first dose (Statistical analysis 2): Based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.698, 0.811]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 3): Based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.735, 0.893]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 4): Based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.698, 0.848]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 5): Based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.69, 0.878]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 6): Based on MMRM model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [0.681, 0.869]Mixed Models Analysis
Secondary
Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
sTST was defined as minutes of sleep from sleep onset to time stopped trying to sleep for the night.
Time frame: Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at first 7 nights | 14.78 minutes | Standard Deviation 54.995 |
| Placebo | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 53.53 minutes | Standard Deviation 74.539 |
| Placebo | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 304.25 minutes | Standard Deviation 91.459 |
| Placebo | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 48.16 minutes | Standard Deviation 75.859 |
| Placebo | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 30.74 minutes | Standard Deviation 70.687 |
| Lemborexant 5 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 76.21 minutes | Standard Deviation 77.714 |
| Lemborexant 5 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 315.52 minutes | Standard Deviation 93.498 |
| Lemborexant 5 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 65.82 minutes | Standard Deviation 71.331 |
| Lemborexant 5 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at first 7 nights | 34.29 minutes | Standard Deviation 54.142 |
| Lemborexant 5 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 39.32 minutes | Standard Deviation 63.548 |
| Lemborexant 10 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 53.22 minutes | Standard Deviation 67.91 |
| Lemborexant 10 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at first 7 nights | 46.01 minutes | Standard Deviation 55.11 |
| Lemborexant 10 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 306.89 minutes | Standard Deviation 88.031 |
| Lemborexant 10 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 78.32 minutes | Standard Deviation 80.741 |
| Lemborexant 10 mg | Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 70.95 minutes | Standard Deviation 70.913 |
Comparison: First 7 Nights After the First Dose (Statistical analysis 1): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: <0.000195% CI: [13.488, 30.579]Mixed Models Analysis
Comparison: First 7 nights after the first dose (Statistical analysis 2): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: <0.000195% CI: [23.258, 40.334]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 3): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.025995% CI: [1.418, 22.102]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 4): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: <0.000195% CI: [11.757, 32.505]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 5): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.003495% CI: [5.781, 28.968]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 6): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.000395% CI: [10.014, 33.359]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 7): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be missing at random (MAR).p-value: 0.003495% CI: [6.14, 30.969]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 8): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline sTST as a covariate. Missing values are not imputed and assumed to be MAR.p-value: 0.000495% CI: [10.137, 35.234]Mixed Models Analysis
Secondary
Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
sSE was defined as percentage of subjective total sleep time (sTST) divided by subjective time spent in bed, calculated as the interval from the time the participant reported attempting to sleep until the time participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO.
Time frame: Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 9.16 percentage of sTST | Standard Deviation 13.644 |
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 10.36 percentage of sTST | Standard Deviation 13.799 |
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 61.34 percentage of sTST | Standard Deviation 17.836 |
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at 1st 7 nights | 2.68 percentage of sTST | Standard Deviation 10.765 |
| Placebo | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 6.11 percentage of sTST | Standard Deviation 12.876 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at 1st 7 nights | 6.61 percentage of sTST | Standard Deviation 10.386 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 63.14 percentage of sTST | Standard Deviation 18.231 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 7.87 percentage of sTST | Standard Deviation 12.263 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 13.03 percentage of sTST | Standard Deviation 13.522 |
| Lemborexant 5 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 15.34 percentage of sTST | Standard Deviation 14.613 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | 13.61 percentage of sTST | Standard Deviation 14.035 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | 15.55 percentage of sTST | Standard Deviation 15.617 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at 1st 7 nights | 8.27 percentage of sTST | Standard Deviation 10.566 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | 9.92 percentage of sTST | Standard Deviation 12.922 |
| Lemborexant 10 mg | Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 62.03 percentage of sTST | Standard Deviation 17.248 |
Comparison: First 7 nights (Statistical analysis 1): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [2.638, 5.961]Mixed Models Analysis
Comparison: First 7 nights (Statistical analysis 2): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [4.133, 7.452]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 3): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.02395% CI: [0.307, 4.146]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 4): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.000395% CI: [1.635, 5.595]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 5): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.000195% CI: [2.068, 6.377]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 6): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [2.22, 6.501]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 7): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.000195% CI: [2.236, 6.861]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 8): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline sSE as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [2.373, 6.96]Mixed Models Analysis
Secondary
Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day.
Time frame: Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 132.49 minutes | Standard Deviation 80.198 |
| Placebo | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at first 7 nights | -6.12 minutes | Standard Deviation 45.893 |
| Placebo | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | -27.08 minutes | Standard Deviation 54.408 |
| Placebo | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | -19.01 minutes | Standard Deviation 50.279 |
| Placebo | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | -32.14 minutes | Standard Deviation 55.279 |
| Lemborexant 5 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at first 7 nights | -20.21 minutes | Standard Deviation 46.015 |
| Lemborexant 5 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | -51.45 minutes | Standard Deviation 67.295 |
| Lemborexant 5 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | -23.42 minutes | Standard Deviation 56.251 |
| Lemborexant 5 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | -42.98 minutes | Standard Deviation 60.064 |
| Lemborexant 5 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 132.77 minutes | Standard Deviation 82.518 |
| Lemborexant 10 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 3 | -39.42 minutes | Standard Deviation 62.783 |
| Lemborexant 10 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at first 7 nights | -23.30 minutes | Standard Deviation 47.7 |
| Lemborexant 10 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 6 | -48.12 minutes | Standard Deviation 68.55 |
| Lemborexant 10 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Baseline | 136.83 minutes | Standard Deviation 87.391 |
| Lemborexant 10 mg | Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6 | Change at Month 1 | -26.82 minutes | Standard Deviation 56.989 |
Comparison: First 7 nights (Statistical analysis 1): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [-21.411, -7.245]Mixed Models Analysis
Comparison: First 7 nights (Statistical analysis 2): Based on MMRM model with factors of age group, region, treatment, visit (First 7 nights), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: <0.000195% CI: [-23.813, -9.626]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 3): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.179695% CI: [-13.568, 2.54]Mixed Models Analysis
Comparison: Month 1 (Statistical analysis 4): Based on MMRM model with factors of age group, region, treatment, visit (Month 1), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.089895% CI: [-15.098, 1.088]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 5): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.002895% CI: [-22.218, -4.631]Mixed Models Analysis
Comparison: Month 3 (Statistical analysis 6): Based on MMRM model with factors of age group, region, treatment, visit (Month 3), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.027795% CI: [-19.053, -1.104]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 7): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.000595% CI: [-27.306, -7.643]Mixed Models Analysis
Comparison: Month 6 (Statistical analysis 8): Based on MMRM model with factors of age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effect, and the study baseline sWASO as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (MNAR/CCMV).p-value: 0.010595% CI: [-22.378, -2.964]Mixed Models Analysis
Secondary
Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period
The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: How sleepy/alert do you feel this morning? Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome.
Time frame: Screening, First and second 7 mornings in follow-up period (Week 52 to 54)
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Screening | 3.63 score on a scale | Standard Deviation 1.393 |
| Placebo | Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Change at First 7 mornings | 1.03 score on a scale | Standard Deviation 1.615 |
| Placebo | Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Change at Second 7 mornings | 0.98 score on a scale | Standard Deviation 1.699 |
| Lemborexant 5 mg | Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Screening | 3.54 score on a scale | Standard Deviation 1.197 |
| Lemborexant 5 mg | Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Change at First 7 mornings | 1.32 score on a scale | Standard Deviation 1.611 |
| Lemborexant 5 mg | Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period | Change at Second 7 mornings | 1.22 score on a scale | Standard Deviation 1.635 |
Secondary
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12
Sleep onset responder was defined as follows: sSOL at study Baseline was \>=30 minutes and mean sSOL at 6 months was \<=20 minutes. Sleep maintenance responder was defined as follows: sWASO at study Baseline was \>=60 minutes and mean sWASO at 6 months was \<=60 minutes and showed a reduction of \> 10 minutes compared to study Baseline.
Time frame: Month 12
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 | Sleep Onset Responders | 34.2 percentage of participants |
| Placebo | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 | Sleep Maintainance Responders | 35.0 percentage of participants |
| Lemborexant 5 mg | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 | Sleep Maintainance Responders | 39.6 percentage of participants |
| Lemborexant 5 mg | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 | Sleep Onset Responders | 37.2 percentage of participants |
Secondary
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6
Sleep onset responder was defined as follows: sSOL at study Baseline was greater than or equal to (\>=) 30 minutes and mean sSOL at 6 months was less than or equal to (\<=) 20 minutes. Sleep maintenance responder was defined as follows: sWASO at study Baseline was \>=60 minutes and mean sWASO at 6 months was \<=60 minutes and showed a reduction of greater than (\>)10 minutes compared to Study Baseline.
Time frame: Month 6
Population: The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to number of participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Sleep Maintenance Responders | 20.4 percentage of responders |
| Placebo | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Sleep Onset Responders | 17.7 percentage of responders |
| Lemborexant 5 mg | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Sleep Onset Responders | 31.2 percentage of responders |
| Lemborexant 5 mg | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Sleep Maintenance Responders | 35.0 percentage of responders |
| Lemborexant 10 mg | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Sleep Onset Responders | 30.1 percentage of responders |
| Lemborexant 10 mg | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 | Sleep Maintenance Responders | 30.0 percentage of responders |
Comparison: Sleep onset responders: Statistical analysis 1p-value: 0.000495% CI: [6.24, 21.1]Cochran-Mantel-Haenszel
Comparison: Sleep Onset Responders: Statistical analysis 2p-value: 0.000995% CI: [5.2, 19.86]Cochran-Mantel-Haenszel
Comparison: Sleep Maintenance Responders: Statistical analysis 3p-value: 0.000295% CI: [6.97, 22.33]Cochran-Mantel-Haenszel
Comparison: Sleep Maintenance Responders: Statistical analysis 4p-value: 0.01195% CI: [2.29, 17.35]Cochran-Mantel-Haenszel
Secondary
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1
sSE was defined as percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At each month beyond Month 1, the change from Baseline was compared to the lower bound of the 95% CI at Month 1. Persistence of efficacy was defined as present if the mean change from Baseline at Month 6 was above the lower bound of the 95% CI at Month 1 for sSE.
Time frame: Baseline, Months 1, 3, 6, 9, and 12
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 3 of exposure | 10.01 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 1 of exposure | 6.35 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 6 of exposure | 11.10 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 9 of exposure | 11.85 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 12 of exposure | 12.61 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 12 of exposure | 13.66 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 9 of exposure | 12.84 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 1 of exposure | 7.32 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 3 of exposure | 10.25 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 | Change at Month 6 of exposure | 11.08 percentage of sTST |
Secondary
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1
sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At each month beyond Month 1, the change from Baseline was compared to either the lower bound of the 95% CI (for sTST) or the upper bound of the 95% CI (for sSOL and sWASO) at Month 1. Persistence of efficacy was defined as present if the mean change from Baseline at Month 6 was above the lower bound of the 95% CI at Month 1 for sTST and below the upper bound of the 95% CI at Month 1 for sSOL and sWASO.
Time frame: Baseline, Month 1, 3, 6, 9, 12
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 9 of exposure | -39.28 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 12 of exposure | 58.15 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 1 of exposure | -17.17 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 12 of exposure | -25.83 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 12 of exposure | -42.87 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 6 of exposure | -24.13 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 6 of exposure | -36.10 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 9 of exposure | -26.00 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 1 of exposure | -17.26 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 1 of exposure | 31.98 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 3 of exposure | -31.34 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 3 of exposure | 49.27 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 6 of exposure | 54.99 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 9 of exposure | 55.41 minutes |
| Placebo | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 3 of exposure | -21.47 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 12 of exposure | 66.50 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 9 of exposure | -27.36 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 12 of exposure | -26.32 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 1 of exposure | -18.69 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 3 of exposure | -28.97 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 6 of exposure | -31.54 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 9 of exposure | -40.39 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sWASO: Change at Month 12 of exposure | -43.76 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 3 of exposure | 53.51 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 9 of exposure | 61.13 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 1 of exposure | -18.64 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 3 of exposure | -21.58 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sSOL: Change at Month 6 of exposure | -22.99 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 1 of exposure | 38.04 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 | sTST: Change at Month 6 of exposure | 56.36 minutes |
Secondary
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7
sSE: percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the subject got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At each month beyond Month 7, the change from Baseline was compared to the lower bound of the 95% CI for sSE at Month 7. Persistence of effect was defined as present if the mean change from Baseline at Month 12 was above the lower bound of the 95% CI at Month 7 for sSE.
Time frame: Baseline, Month 7, 9, 12
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Change at Month 9 of exposure | 16.54 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Change at Month 7 of exposure | 12.88 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Change at Month 12 of exposure | 16.34 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Change at Month 7 of exposure | 15.12 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Change at Month 9 of exposure | 16.49 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 | Change at Month 12 of exposure | 16.82 percentage of sTST |
Secondary
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7
sSOL is defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO: sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At each month beyond Month 7, the change from Baseline was compared to either the lower bound of the 95% CI for sTST or the upper bound of the 95% CI (for sSOL and sWASO) at Month 7. Persistence of effect was defined as present if the mean change from Baseline at Month 12 was above the lower bound of the 95% CI at Month 7 for sTST and below the upper bound of the 95% CI at Month 7 for sSOL and sWASO.
Time frame: Baseline, Month 7, 9, 12
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sSOL: Change at Month 7 of exposure | -28.55 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sWASO: Change at Month 7 of exposure | -45.62 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sWASO: Change at Month 9 of exposure | -47.70 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sSOL: Change at Month 9 of exposure | -32.10 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sWASO: Change at Month 12 of exposure | -48.46 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sSOL: Change at Month 12 of exposure | -31.40 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sTST: Change at Month 7 of exposure | 75.00 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sTST: Change at Month 9 of exposure | 78.69 minutes |
| Placebo | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sTST: Change at Month 12 of exposure | 78.61 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sTST: Change at Month 12 of exposure | 83.61 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sSOL: Change at Month 9 of exposure | -30.91 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sSOL: Change at Month 12 of exposure | -31.33 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sWASO: Change at Month 7 of exposure | -43.09 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sTST: Change at Month 7 of exposure | 76.95 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sTST: Change at Month 9 of exposure | 81.24 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sWASO: Change at Month 9 of exposure | -48.87 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sWASO: Change at Month 12 of exposure | -49.28 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7 | sSOL: Change at Month 7 of exposure | -29.46 minutes |
Secondary
Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1
sSE was defined as percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At 3 and 6 months of exposure, the change from Baseline was compared to the lower bound of the 95% CI for sSE at 1 month of exposure. Persistence of effect was defined as present if the mean change from Baseline at 6 months of exposure was above the lower bound of the 95% CI at 1 month of exposure for sSE.
Time frame: Baseline, Month 1, 3, 6
Population: On-treatment FAS was the group of participants who received at least 1 dose of lemborexant and had at least 1 post dose primary efficacy measurement. Overall Participants Analyzed here is based on the number in the On-Treatment FAS. Hence these numbers include the lemborexant data from the participants re-randomized from placebo in Period 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Change at Month 1 of exposure | 6.35 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Change at Month 3 of exposure | 10.01 percentage of sTST |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Change at Month 6 of exposure | 11.10 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Change at Month 1 of exposure | 7.32 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Change at Month 3 of exposure | 10.25 percentage of sTST |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1 | Change at Month 6 of exposure | 11.08 percentage of sTST |
Secondary
Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1
sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO: sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At 3 and 6 months of exposure, the change from Baseline was compared to either the lower bound of the 95% CI for sTST or the upper bound of the 95% CI (for sSOL and sWASO) at 1 month of exposure. Persistence of effect was defined as present if the mean change from Baseline at 6 months of exposure was above the lower bound of the 95% CI at 1 month of exposure for sTST and below the upper bound of the 95% CI at 1 month of exposure for sSOL and sWASO.
Time frame: Baseline, Month 1, 3, 6
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sTST: Change at Month 1 of exposure | 31.98 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sWASO: Change at Month 6 of exposure | -36.10 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sSOL: Change at Month 6 of exposure | -24.13 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sTST: Change at Month 6 of exposure | 54.99 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sWASO: Change at Month 1 of exposure | -17.26 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sWASO: Change at Month 3 of exposure | -31.34 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sSOL: Change at Month 1 of exposure | -17.17 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sTST: Change at Month 3 of exposure | 49.27 minutes |
| Placebo | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sSOL: Change at Month 3 of exposure | -21.47 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sTST: Change at Month 6 of exposure | 56.36 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sWASO: Change at Month 1 of exposure | -18.69 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sWASO: Change at Month 3 of exposure | -28.97 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sWASO: Change at Month 6 of exposure | -31.54 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sTST: Change at Month 3 of exposure | 53.51 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sSOL: Change at Month 1 of exposure | -18.64 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sSOL: Change at Month 3 of exposure | -21.58 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sSOL: Change at Month 6 of exposure | -22.99 minutes |
| Lemborexant 5 mg | Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1 | sTST: Change at Month 1 of exposure | 38.04 minutes |
Secondary
Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period
Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset.
Time frame: First 3 nights, first and Last 7 nights of the follow up period (Week 52 to 54)
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of first 3 nights | 40.35 minutes | Standard Deviation 48.661 |
| Placebo | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean sSOL of the first 7 nights | 41.35 minutes | Standard Deviation 38.967 |
| Placebo | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean sSOL of the second 7 nights | 44.10 minutes | Standard Deviation 38.03 |
| Lemborexant 5 mg | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of first 3 nights | 41.73 minutes | Standard Deviation 55.694 |
| Lemborexant 5 mg | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean sSOL of the first 7 nights | 41.90 minutes | Standard Deviation 47.826 |
| Lemborexant 5 mg | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean sSOL of the second 7 nights | 41.30 minutes | Standard Deviation 47.471 |
Secondary
Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period
Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day.
Time frame: First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54)
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of first 3 nights | 86.66 minutes | Standard Deviation 80.038 |
| Placebo | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of the first 7 nights | 91.56 minutes | Standard Deviation 81.738 |
| Placebo | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of the Last 7 nights | 92.62 minutes | Standard Deviation 82.672 |
| Lemborexant 5 mg | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of first 3 nights | 97.88 minutes | Standard Deviation 83.302 |
| Lemborexant 5 mg | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of the first 7 nights | 95.79 minutes | Standard Deviation 79.784 |
| Lemborexant 5 mg | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period | Mean of the Last 7 nights | 98.19 minutes | Standard Deviation 80.668 |
Secondary
Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period
Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset.
Time frame: First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54)
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 3 nights | 9.46 percentage of participants |
| Placebo | Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 7 nights | 11.94 percentage of participants |
| Placebo | Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | Average of second 7 nights | 11.71 percentage of participants |
| Lemborexant 5 mg | Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 3 nights | 9.38 percentage of participants |
| Lemborexant 5 mg | Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 7 nights | 10.53 percentage of participants |
| Lemborexant 5 mg | Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period | Average of second 7 nights | 9.38 percentage of participants |
Secondary
Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period
Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day.
Time frame: First 3 nights, First and Last 7 nights of the follow up period (Week 52 to 54)
Population: Overall participants analyzed based on number in On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement). Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 3 nights | 11.26 percentage of participants |
| Placebo | Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 7 nights | 12.39 percentage of participants |
| Placebo | Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | Average of second 7 nights | 13.51 percentage of participants |
| Lemborexant 5 mg | Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 3 nights | 12.59 percentage of participants |
| Lemborexant 5 mg | Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | Average of first 7 nights | 14.19 percentage of participants |
| Lemborexant 5 mg | Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period | Average of second 7 nights | 11.90 percentage of participants |