Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: lemborexant 5 milligrams (mg) Lemborexant 5 mg will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep. |
Drug: lemborexant
|
Experimental: lemborexant 10 mg Lemborexant 10 mg will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep. |
Drug: lemborexant
|
Placebo Comparator: Placebo matched to lemborexant Lemborexant-matched placebo will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep. |
Drug: Placebo
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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 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.
- 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.
Eligibility Criteria
Criteria
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
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International Restless Legs Scale (IRLS) score >=16
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Epworth Sleepiness Scale (ESS) score >15
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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
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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
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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
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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
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Facility # 1 | Chandler | Arizona | United States | 85224 |
2 | Facility # 2 | Chandler | Arizona | United States | 85224 |
3 | Facility # 1 | Rogers | Arkansas | United States | 72758 |
4 | Facility # 1 | Beverly Hills | California | United States | 90210 |
5 | Facility # 2 | Los Angeles | California | United States | 90048 |
6 | Facility # 1 | Los Angeles | California | United States | 90069 |
7 | Facility # 1 | Redlands | California | United States | 92374 |
8 | Facility # 1 | Sacramento | California | United States | 95821 |
9 | Facility # 1 | Santa Monica | California | United States | 90404 |
10 | Facility # 1 | Torrance | California | United States | 90502 |
11 | Facility # 1 | Colorado Springs | Colorado | United States | 80909 |
12 | Facility # 1 | Celebration | Florida | United States | 34747 |
13 | Facility # 1 | Hialeah | Florida | United States | 33016 |
14 | Facility # 1 | Homestead | Florida | United States | 33030 |
15 | Facility # 1 | Jacksonville | Florida | United States | 32256 |
16 | Facility # 1 | Lauderhill | Florida | United States | 33319 |
17 | Facility # 1 | Maitland | Florida | United States | 32751 |
18 | Innovative Clinical Research Inc | Miami | Florida | United States | 33161 |
19 | Facility # 1 | Ocala | Florida | United States | 34471 |
20 | Facility # 1 | Orlando | Florida | United States | 32801 |
21 | Facility # 1 | Oviedo | Florida | United States | 32765 |
22 | Facility # 1 | Pinellas Park | Florida | United States | 33781 |
23 | Facility # 1 | Tampa | Florida | United States | 33634 |
24 | Facility # 1 | The Villages | Florida | United States | 32162 |
25 | Facility # 1 | Evansville | Indiana | United States | 47714 |
26 | Facility # 1 | Elkridge | Maryland | United States | 21075 |
27 | Facility # 1 | Quincy | Massachusetts | United States | 2169 |
28 | Facility # 1 | Kansas City | Missouri | United States | 64114 |
29 | Facility # 1 | Albuquerque | New Mexico | United States | 87109 |
30 | Facility # 1 | Brooklyn | New York | United States | 11235 |
31 | Facility # 1 | Hickory | North Carolina | United States | 28601 |
32 | Facility # 1 | Dayton | Ohio | United States | 45417 |
33 | Facility # 2 | Oklahoma City | Oklahoma | United States | 73103 |
34 | Facility # 1 | Oklahoma City | Oklahoma | United States | 73112 |
35 | Facility # 1 | Portland | Oregon | United States | 97210 |
36 | Facility # 1 | Lincoln | Rhode Island | United States | 2865 |
37 | Facility # 1 | Memphis | Tennessee | United States | 38119 |
38 | Facility # 1 | Austin | Texas | United States | 78705 |
39 | Facility # 2 | Austin | Texas | United States | 78731 |
40 | Facility # 1 | Fort Worth | Texas | United States | 76135 |
41 | Facility # 1 | San Angelo | Texas | United States | 76904 |
42 | Facility # 1 | Seattle | Washington | United States | 98101 |
43 | Facility # 1 | Kelowna | British Columbia | Canada | |
44 | Facility # 1 | Toronto | Ontario | Canada | |
45 | Facility # 1 | Point-Claire | Quebec | Canada | |
46 | Facility # 1 | Sherbrooke | Quebec | Canada | |
47 | Facility # 1 | Oulu | Oulun Laani | Finland | |
48 | Facility # 1 | Helsinki | Finland | ||
49 | Facility # 1 | Kuopio | Finland | ||
50 | Facility # 1 | Tampere | Finland | ||
51 | Facility # 1 | Turku | Finland | ||
52 | Facility # 2 | Turku | Finland | ||
53 | Facility # 1 | Bochum | Nordrhein-Westfalen | Germany | |
54 | Facility # 1 | Leipzig | Sachsen | Germany | |
55 | Facility # 1 | Berlin | Germany | ||
56 | Facility # 2 | Berlin | Germany | ||
57 | Facility # 3 | Berlin | Germany | ||
58 | Facility # 1 | Hamburg | Germany | ||
59 | Facility # 1 | Hannover | Germany | ||
60 | Facility # 1 | Milano | Lombardia | Italy | |
61 | Facility # 1 | Siena | Toscana | Italy | |
62 | Facility # 1 | Roma | Italy | ||
63 | Eisai Trail Site 1 | Maebashi | Gunma | Japan | |
64 | Eisai Trail Site 1 | Sapporo | Hokkaido | Japan | |
65 | Eisai Trail Site 2 | Sapporo | Hokkaido | Japan | |
66 | Eisai Trail Site 3 | Sapporo | Hokkaido | Japan | |
67 | Eisai Trail Site 4 | Sapporo | Hokkaido | Japan | |
68 | Eisai Trail Site 1 | Sagamihara | Kanagawa | Japan | |
69 | Eisai Trial Site 1 | Yokohama | Kanagawa | Japan | |
70 | Eisai Trial Site 2 | Yokohama | Kanagawa | Japan | |
71 | Eisai Trial Site 3 | Yokohama | Kanagawa | Japan | |
72 | Eisai Trail Site 1 | Tokorozawa | Saitama | Japan | |
73 | Eisai Trail Site 1 | Arakawa | Tokyo | Japan | |
74 | Eisai Trail Site 1 | Katsushika | Tokyo | Japan | |
75 | Eisai Trail Site 1 | Minato | Tokyo | Japan | |
76 | Eisai Trail Site 2 | Minato | Tokyo | Japan | |
77 | Eisai Trail Site 1 | Musashino | Tokyo | Japan | |
78 | Eisai Trail Site 1 | Ota | Tokyo | Japan | |
79 | Eisai Trail Site 2 | Ota | Tokyo | Japan | |
80 | Eisai Trail Site 3 | Ota | Tokyo | Japan | |
81 | Eisai Trail Site 1 | Shibuya | Tokyo | Japan | |
82 | Eisai Trail Site 1 | Shinagawa | Tokyo | Japan | |
83 | Eisai Trail Site 2 | Shinagawa | Tokyo | Japan | |
84 | Eisai Trail Site 1 | Shinjuku | Tokyo | Japan | |
85 | Eisai Trail Site 2 | Shinjuku | Tokyo | Japan | |
86 | Eisai Trail Site 1 | Toshima | Tokyo | Japan | |
87 | Facility # 1 | Seongnam-si | Gyeonggido | Korea, Republic of | |
88 | Facility # 1 | Suwon | Gyeonggido | Korea, Republic of | |
89 | Facility # 1 | Daegu | Korea, Republic of | ||
90 | Facility # 1 | Seoul | Korea, Republic of | ||
91 | Facility # 3 | Seoul | Korea, Republic of | ||
92 | Facility # 1 | Monterrey | Nuevo Leon | Mexico | |
93 | Facility # 1 | Wellington | North Island | New Zealand | |
94 | Facility # 1 | Christchurch | South Island | New Zealand | |
95 | Facility # 1 | Dunedin | South Island | New Zealand | |
96 | Facility # 1 | Auckland | New Zealand | ||
97 | Facility # 1 | Rotorua | New Zealand | ||
98 | Facility # 1 | Tarnow | Malopolskie | Poland | |
99 | Facility # 1 | Warszawa | Mazowieckie | Poland | |
100 | Facility # 1 | Gdansk | Poland | ||
101 | Facility # 1 | Katowice | Poland | ||
102 | Facility # 1 | Ostroda | Poland | ||
103 | Facility # 2 | Warszawa | Poland | ||
104 | Facility # 3 | Warszawa | Poland | ||
105 | Facility # 1 | Brasov | Romania | ||
106 | Facility # 1 | Bucharest | Romania | ||
107 | Facility # 1 | Constanta | Romania | ||
108 | Facility # 1 | Sibiu | Romania | ||
109 | Facility # 1 | Targu Mures | Romania | ||
110 | Facility # 1 | Palma de Mallorca | Baleares | Spain | |
111 | Facility # 1 | Torrejon de Ardoz | Madrid | Spain | |
112 | Facility # 1 | Quart de Poblet | Valencia | Spain | |
113 | Facility # 1 | Barcelona | Spain | ||
114 | Facility # 1 | Valencia | Spain |
Sponsors and Collaborators
- Eisai Inc.
Investigators
- Study Director: Eisai Medical Information, Eisai Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- E2006-G000-303
- 2015-001463-39
Study Results
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. |
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Pre-assignment Detail | A total of 2059 participants were screened, of which 1088 were screen failures and 971 participants were randomized to receive study treatment. |
Arm/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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 milligram (mg) or lemborexant 10 mg up to Month 12. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Period Title: Placebo-Controlled Treatment (6 Months) | |||
STARTED | 325 | 323 | 323 |
Treated | 321 | 319 | 319 |
Safety Analysis Set | 319 | 314 | 314 |
COMPLETED | 261 | 254 | 235 |
NOT COMPLETED | 64 | 69 | 88 |
Period Title: Placebo-Controlled Treatment (6 Months) | |||
STARTED | 0 | 384 | 352 |
COMPLETED | 0 | 346 | 321 |
NOT COMPLETED | 0 | 38 | 31 |
Baseline Characteristics
Arm/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg | Total |
---|---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Total of all reporting groups |
Overall Participants | 318 | 316 | 315 | 949 |
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
54.5
(14.01)
|
54.2
(13.74)
|
54.8
(13.68)
|
54.5
(13.80)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
216
67.9%
|
209
66.1%
|
222
70.5%
|
647
68.2%
|
Male |
102
32.1%
|
107
33.9%
|
93
29.5%
|
302
31.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
34
10.7%
|
19
6%
|
19
6%
|
72
7.6%
|
Not Hispanic or Latino |
284
89.3%
|
297
94%
|
296
94%
|
877
92.4%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race/Ethnicity, Customized (Count of Participants) | ||||
White |
232
73%
|
222
70.3%
|
225
71.4%
|
679
71.5%
|
Black or African American |
23
7.2%
|
27
8.5%
|
26
8.3%
|
76
8%
|
Japanese |
54
17%
|
53
16.8%
|
54
17.1%
|
161
17%
|
Chinese |
0
0%
|
3
0.9%
|
1
0.3%
|
4
0.4%
|
Other Asian |
5
1.6%
|
5
1.6%
|
3
1%
|
13
1.4%
|
American Indian or Alaska Native |
0
0%
|
1
0.3%
|
2
0.6%
|
3
0.3%
|
Native Hawaiian or other Pacific Islander |
0
0%
|
1
0.3%
|
0
0%
|
1
0.1%
|
Other |
4
1.3%
|
4
1.3%
|
4
1.3%
|
12
1.3%
|
Outcome Measures
Title | Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 |
---|---|
Description | sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. |
Time Frame | Baseline and Month 6 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
64.03
(45.209)
|
62.19
(45.674)
|
64.97
(44.020)
|
Change at Month 6 |
-16.57
(35.313)
|
-29.39
(33.261)
|
-32.49
(35.962)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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]). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | least squares geometric mean (LSGM)ratio |
Estimated Value | 0.732 | |
Confidence Interval |
(2-Sided) 95% 0.636 to 0.843 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.701 | |
Confidence Interval |
(2-Sided) 95% 0.607 to 0.810 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
64.03
(45.209)
|
62.19
(45.674)
|
64.97
(44.020)
|
Change at 1st 7 nights |
-4.11
(27.671)
|
-16.86
(27.784)
|
-18.89
(31.003)
|
Change at Month 1 |
-11.48
(32.726)
|
-19.41
(32.221)
|
-24.06
(35.234)
|
Change at Month 3 |
-13.84
(35.277)
|
-25.08
(34.081)
|
-27.94
(39.192)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.781 | |
Confidence Interval |
(2-Sided) 95% 0.725 to 0.842 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.752 | |
Confidence Interval |
(2-Sided) 95% 0.698 to 0.811 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.810 | |
Confidence Interval |
(2-Sided) 95% 0.735 to 0.893 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.770 | |
Confidence Interval |
(2-Sided) 95% 0.698 to 0.848 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.778 | |
Confidence Interval |
(2-Sided) 95% 0.690 to 0.878 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSGM ratio |
Estimated Value | 0.770 | |
Confidence Interval |
(2-Sided) 95% 0.681 to 0.869 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
61.34
(17.836)
|
63.14
(18.231)
|
62.03
(17.248)
|
Change at 1st 7 nights |
2.68
(10.765)
|
6.61
(10.386)
|
8.27
(10.566)
|
Change at Month 1 |
6.11
(12.876)
|
7.87
(12.263)
|
9.92
(12.922)
|
Change at Month 3 |
9.16
(13.644)
|
13.03
(13.522)
|
13.61
(14.035)
|
Change at Month 6 |
10.36
(13.799)
|
15.34
(14.613)
|
15.55
(15.617)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 4.299 | |
Confidence Interval |
(2-Sided) 95% 2.638 to 5.961 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.848 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 5.793 | |
Confidence Interval |
(2-Sided) 95% 4.133 to 7.452 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.846 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0230 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 2.227 | |
Confidence Interval |
(2-Sided) 95% 0.307 to 4.146 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.979 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0003 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 3.615 | |
Confidence Interval |
(2-Sided) 95% 1.635 to 5.595 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.010 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 4.222 | |
Confidence Interval |
(2-Sided) 95% 2.068 to 6.377 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.099 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 4.361 | |
Confidence Interval |
(2-Sided) 95% 2.220 to 6.501 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.092 |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 4.549 | |
Confidence Interval |
(2-Sided) 95% 2.236 to 6.861 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.179 |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 4.667 | |
Confidence Interval |
(2-Sided) 95% 2.373 to 6.960 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.170 |
|
Estimation Comments |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
132.49
(80.198)
|
132.77
(82.518)
|
136.83
(87.391)
|
Change at first 7 nights |
-6.12
(45.893)
|
-20.21
(46.015)
|
-23.30
(47.700)
|
Change at Month 1 |
-19.01
(50.279)
|
-23.42
(56.251)
|
-26.82
(56.989)
|
Change at Month 3 |
-27.08
(54.408)
|
-42.98
(60.064)
|
-39.42
(62.783)
|
Change at Month 6 |
-32.14
(55.279)
|
-51.45
(67.295)
|
-48.12
(68.550)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean (LSM) Difference |
Estimated Value | -14.328 | |
Confidence Interval |
(2-Sided) 95% -21.411 to -7.245 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.614 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -16.720 | |
Confidence Interval |
(2-Sided) 95% -23.813 to -9.626 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.619 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1796 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -5.514 | |
Confidence Interval |
(2-Sided) 95% -13.568 to 2.540 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.109 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0898 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -7.005 | |
Confidence Interval |
(2-Sided) 95% -15.098 to 1.088 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.129 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0028 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -13.424 | |
Confidence Interval |
(2-Sided) 95% -22.218 to -4.631 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.486 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0277 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -10.079 | |
Confidence Interval |
(2-Sided) 95% -19.053 to -1.104 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.578 |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0005 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -17.474 | |
Confidence Interval |
(2-Sided) 95% -27.306 to -7.643 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.014 |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0105 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -12.671 | |
Confidence Interval |
(2-Sided) 95% -22.378 to -2.964 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.951 |
|
Estimation Comments |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
304.25
(91.459)
|
315.52
(93.498)
|
306.89
(88.031)
|
Change at first 7 nights |
14.78
(54.995)
|
34.29
(54.142)
|
46.01
(55.110)
|
Change at Month 1 |
30.74
(70.687)
|
39.32
(63.548)
|
53.22
(67.910)
|
Change at Month 3 |
48.16
(75.859)
|
65.82
(71.331)
|
70.95
(70.913)
|
Change at Month 6 |
53.53
(74.539)
|
76.21
(77.714)
|
78.32
(80.741)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 22.034 | |
Confidence Interval |
(2-Sided) 95% 13.488 to 30.579 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.354 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 31.796 | |
Confidence Interval |
(2-Sided) 95% 23.258 to 40.334 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.350 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0259 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 11.760 | |
Confidence Interval |
(2-Sided) 95% 1.418 to 22.102 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.269 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 22.131 | |
Confidence Interval |
(2-Sided) 95% 11.757 to 32.505 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.286 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0034 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 17.374 | |
Confidence Interval |
(2-Sided) 95% 5.781 to 28.968 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.906 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0003 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 21.686 | |
Confidence Interval |
(2-Sided) 95% 10.014 to 33.359 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.946 |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0034 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 18.555 | |
Confidence Interval |
(2-Sided) 95% 6.140 to 30.969 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.324 |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0004 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 22.686 | |
Confidence Interval |
(2-Sided) 95% 10.137 to 35.234 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.392 |
|
Estimation Comments |
Title | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Sleep Onset Responders |
17.7
|
31.2
|
30.1
|
Sleep Maintenance Responders |
20.4
|
35.0
|
30.0
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | Sleep onset responders: Statistical analysis 1 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0004 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Difference of percentage |
Estimated Value | 13.67 | |
Confidence Interval |
(2-Sided) 95% 6.24 to 21.10 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | Sleep Onset Responders: Statistical analysis 2 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0009 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Difference of percentage |
Estimated Value | 12.53 | |
Confidence Interval |
(2-Sided) 95% 5.20 to 19.86 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | Sleep Maintenance Responders: Statistical analysis 3 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0002 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Difference of percentage |
Estimated Value | 14.65 | |
Confidence Interval |
(2-Sided) 95% 6.97 to 22.33 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | Sleep Maintenance Responders: Statistical analysis 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0110 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Difference of percentage |
Estimated Value | 9.82 | |
Confidence Interval |
(2-Sided) 95% 2.29 to 17.35 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Sleep Onset Responders |
34.2
10.8%
|
37.2
11.8%
|
Sleep Maintainance Responders |
35.0
11%
|
39.6
12.5%
|
Title | Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
11.0
(2.10)
|
11.4
(2.02)
|
11.0
(2.15)
|
Change at Month 1 |
-3.1
(3.41)
|
-4.1
(3.66)
|
-4.2
(4.01)
|
Change at Month 3 |
-3.7
(3.55)
|
-5.2
(3.88)
|
-5.2
(4.05)
|
Change at Month 6 |
-4.3
(3.66)
|
-6.0
(3.76)
|
-5.7
(4.00)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0137 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -0.71 | |
Confidence Interval |
(2-Sided) 95% -1.27 to -0.15 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.287 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0011 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -0.94 | |
Confidence Interval |
(2-Sided) 95% -1.51 to -0.38 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.289 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -1.16 | |
Confidence Interval |
(2-Sided) 95% -1.75 to -0.57 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.302 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -1.36 | |
Confidence Interval |
(2-Sided) 95% -1.96 to -0.76 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.305 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -1.30 | |
Confidence Interval |
(2-Sided) 95% -1.90 to -0.71 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.302 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -1.32 | |
Confidence Interval |
(2-Sided) 95% -1.92 to -0.71 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.307 |
|
Estimation Comments |
Title | Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
35.2
(13.55)
|
37.4
(12.74)
|
36.0
(13.01)
|
Change at Month 1 |
-3.9
(11.62)
|
-6.6
(11.83)
|
-6.4
(13.68)
|
Change at Month 3 |
-4.3
(11.37)
|
-7.7
(12.97)
|
-7.9
(13.56)
|
Change at Month 6 |
-6.3
(12.07)
|
-10.1
(13.56)
|
-8.9
(14.91)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0670 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -1.66 | |
Confidence Interval |
(2-Sided) 95% -3.44 to 0.12 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.905 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0257 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -2.04 | |
Confidence Interval |
(2-Sided) 95% -3.83 to -0.25 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.913 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0206 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -2.18 | |
Confidence Interval |
(2-Sided) 95% -4.02 to -0.34 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.939 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0014 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -3.04 | |
Confidence Interval |
(2-Sided) 95% -4.91 to -1.18 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.950 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0134 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -2.50 | |
Confidence Interval |
(2-Sided) 95% -4.48 to -0.52 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.112 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0128 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | -2.56 | |
Confidence Interval |
(2-Sided) 95% -4.57 to -0.54 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.026 |
|
Estimation Comments |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|---|
Arm/Group Description | 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. | Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). | Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2). |
Measure Participants | 318 | 316 | 315 |
Baseline |
3.94
(1.558)
|
3.93
(1.349)
|
3.93
(1.324)
|
Change at First 7 nights |
0.15
(0.991)
|
0.36
(0.964)
|
0.33
(1.018)
|
Change at Month 1 |
0.44
(1.233)
|
0.53
(1.172)
|
0.55
(1.298)
|
Change at Month 3 |
0.62
(1.366)
|
0.74
(1.325)
|
0.90
(1.452)
|
Change at Month 6 |
0.79
(1.392)
|
0.98
(1.463)
|
1.05
(1.524)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0067 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.205 | |
Confidence Interval |
(2-Sided) 95% 0.057 to 0.353 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.076 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0237 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.171 | |
Confidence Interval |
(2-Sided) 95% 0.023 to 0.320 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.076 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4120 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.077 | |
Confidence Interval |
(2-Sided) 95% -0.107 to 0.261 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.094 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4347 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.073 | |
Confidence Interval |
(2-Sided) 95% -0.111 to 0.258 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.094 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4992 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.074 | |
Confidence Interval |
(2-Sided) 95% -0.141 to 0.289 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.109 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0208 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.255 | |
Confidence Interval |
(2-Sided) 95% 0.039 to 0.471 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.110 |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 5 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2248 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.144 | |
Confidence Interval |
(2-Sided) 95% -0.089 to 0.378 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.119 |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | Placebo, Lemborexant 10 mg |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0298 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSM Difference |
Estimated Value | 0.261 | |
Confidence Interval |
(2-Sided) 95% 0.026 to 0.497 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.120 |
|
Estimation Comments |
Title | 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) |
---|---|
Description | |
Time Frame | Baseline, First 7 nights (approximately Week 1) in active treatment period |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Baseline |
4.15
(1.516)
|
4.16
(1.428)
|
Change at First 7 nights |
0.36
(0.964)
|
0.33
(1.018)
|
Title | 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 |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Screening |
3.63
(1.393)
|
3.54
(1.197)
|
Change at First 7 mornings |
1.03
(1.615)
|
1.32
(1.611)
|
Change at Second 7 mornings |
0.98
(1.699)
|
1.22
(1.635)
|
Title | Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Baseline |
4.15
(1.516)
|
4.16
(1.428)
|
Change at Month 1 of exposure |
0.46
(1.082)
|
0.42
(1.223)
|
Change at Month 3 of exposure |
0.60
(1.264)
|
0.70
(1.356)
|
Change at Month 6 of exposure |
0.78
(1.424)
|
0.86
(1.461)
|
Change at Month 9 of exposure |
1.00
(1.512)
|
1.08
(1.489)
|
Change at Month 12 of exposure |
1.11
(1.499)
|
1.31
(1.604)
|
Title | Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Mean of first 3 nights |
40.35
(48.661)
|
41.73
(55.694)
|
Mean sSOL of the first 7 nights |
41.35
(38.967)
|
41.90
(47.826)
|
Mean sSOL of the second 7 nights |
44.10
(38.030)
|
41.30
(47.471)
|
Title | Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Mean of first 3 nights |
86.66
(80.038)
|
97.88
(83.302)
|
Mean of the first 7 nights |
91.56
(81.738)
|
95.79
(79.784)
|
Mean of the Last 7 nights |
92.62
(82.672)
|
98.19
(80.668)
|
Title | 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 |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Average of first 3 nights |
9.46
3%
|
9.38
3%
|
Average of first 7 nights |
11.94
3.8%
|
10.53
3.3%
|
Average of second 7 nights |
11.71
3.7%
|
9.38
3%
|
Title | 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 |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Average of first 3 nights |
11.26
3.5%
|
12.59
4%
|
Average of first 7 nights |
12.39
3.9%
|
14.19
4.5%
|
Average of second 7 nights |
13.51
4.2%
|
11.90
3.8%
|
Title | Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
sSOL: Change at Month 1 of exposure |
-17.17
|
-18.64
|
sSOL: Change at Month 3 of exposure |
-21.47
|
-21.58
|
sSOL: Change at Month 6 of exposure |
-24.13
|
-22.99
|
sSOL: Change at Month 9 of exposure |
-26.00
|
-27.36
|
sSOL: Change at Month 12 of exposure |
-25.83
|
-26.32
|
sWASO: Change at Month 1 of exposure |
-17.26
|
-18.69
|
sWASO: Change at Month 3 of exposure |
-31.34
|
-28.97
|
sWASO: Change at Month 6 of exposure |
-36.10
|
-31.54
|
sWASO: Change at Month 9 of exposure |
-39.28
|
-40.39
|
sWASO: Change at Month 12 of exposure |
-42.87
|
-43.76
|
sTST: Change at Month 1 of exposure |
31.98
|
38.04
|
sTST: Change at Month 3 of exposure |
49.27
|
53.51
|
sTST: Change at Month 6 of exposure |
54.99
|
56.36
|
sTST: Change at Month 9 of exposure |
55.41
|
61.13
|
sTST: Change at Month 12 of exposure |
58.15
|
66.50
|
Title | Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Change at Month 1 of exposure |
6.35
|
7.32
|
Change at Month 3 of exposure |
10.01
|
10.25
|
Change at Month 6 of exposure |
11.10
|
11.08
|
Change at Month 9 of exposure |
11.85
|
12.84
|
Change at Month 12 of exposure |
12.61
|
13.66
|
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
sSOL: Change at Month 7 of exposure |
-28.55
|
-29.46
|
sSOL: Change at Month 9 of exposure |
-32.10
|
-30.91
|
sSOL: Change at Month 12 of exposure |
-31.40
|
-31.33
|
sWASO: Change at Month 7 of exposure |
-45.62
|
-43.09
|
sWASO: Change at Month 9 of exposure |
-47.70
|
-48.87
|
sWASO: Change at Month 12 of exposure |
-48.46
|
-49.28
|
sTST: Change at Month 7 of exposure |
75.00
|
76.95
|
sTST: Change at Month 9 of exposure |
78.69
|
81.24
|
sTST: Change at Month 12 of exposure |
78.61
|
83.61
|
Title | Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Change at Month 7 of exposure |
12.88
|
15.12
|
Change at Month 9 of exposure |
16.54
|
16.49
|
Change at Month 12 of exposure |
16.34
|
16.82
|
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
sSOL: Change at Month 1 of exposure |
-17.17
|
-18.64
|
sSOL: Change at Month 3 of exposure |
-21.47
|
-21.58
|
sSOL: Change at Month 6 of exposure |
-24.13
|
-22.99
|
sWASO: Change at Month 1 of exposure |
-17.26
|
-18.69
|
sWASO: Change at Month 3 of exposure |
-31.34
|
-28.97
|
sWASO: Change at Month 6 of exposure |
-36.10
|
-31.54
|
sTST: Change at Month 1 of exposure |
31.98
|
38.04
|
sTST: Change at Month 3 of exposure |
49.27
|
53.51
|
sTST: Change at Month 6 of exposure |
54.99
|
56.36
|
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Lemborexant 5 mg | Lemborexant 10 mg |
---|---|---|
Arm/Group Description | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). |
Measure Participants | 444 | 437 |
Change at Month 1 of exposure |
6.35
|
7.32
|
Change at Month 3 of exposure |
10.01
|
10.25
|
Change at Month 6 of exposure |
11.10
|
11.08
|
Adverse Events
Time Frame | From start of study drug administration up to Week 54 | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2. | |||||
Arm/Group Title | Placebo | Lemborexant 5 mg | Lemborexant 10 mg | |||
Arm/Group Description | Participants received placebo matched to lemborexant tablet, orally, once daily for up to 6 months. Then they were re-randomized to Lemborexant 5 mg or Lemborexant 10 mg. | Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2). | |||
All Cause Mortality |
||||||
Placebo | Lemborexant 5 mg | Lemborexant 10 mg | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/319 (0%) | 0/447 (0%) | 0/437 (0%) | |||
Serious Adverse Events |
||||||
Placebo | Lemborexant 5 mg | Lemborexant 10 mg | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/319 (1.6%) | 18/447 (4%) | 16/437 (3.7%) | |||
Cardiac disorders | ||||||
Angina Pectoris | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Acute myocardial infarction | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Atrial fibrillation | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Extrasystoles | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Endocrine disorders | ||||||
Goitre | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 0/437 (0%) | 0 |
Eye disorders | ||||||
Diabetic Retinopathy | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Floppy eyelid syndrome | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Gastrointestinal disorders | ||||||
Alcoholic pancreatitis | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Gastrointestinal haemorrhage | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Gastrointestinal inflammation | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Hiatus hernia | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
General disorders | ||||||
Chest Pain | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Cyst | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 0/437 (0%) | 0 |
Inflammation | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Non-cardiac chest pain | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Hepatobiliary disorders | ||||||
Cholestasis | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Hepatotoxicity | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Infections and infestations | ||||||
Cystitis | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Pneumonia | 1/319 (0.3%) | 1 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Postoperative Wound Infection | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Erysipelas | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||
Fall | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 1/437 (0.2%) | 1 |
Lower Limb Fracture | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Pelvic Fracture | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 0/437 (0%) | 0 |
Rib Fracture | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Tibia Fracture | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 0/437 (0%) | 0 |
Ankle fracture | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 1/437 (0.2%) | 1 |
Hand fracture | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Meniscus injury | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Intentional Overdose | 0/319 (0%) | 0 | 1/447 (0.2%) | 7 | 0/437 (0%) | 0 |
Metabolism and nutrition disorders | ||||||
Type 2 Diabetes Mellitus | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Musculoskeletal and connective tissue disorders | ||||||
Jaw Cyst | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 0/437 (0%) | 0 |
Jaw Fistula | 1/319 (0.3%) | 1 | 0/447 (0%) | 0 | 0/437 (0%) | 0 |
Osteoarthritis | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 3/437 (0.7%) | 3 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Intraductal Proliferative Breast Lesion | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Breast cancer | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Nervous system disorders | ||||||
Cerebrovascular Accident | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Diabetic Neuropathy | 0/319 (0%) | 0 | 2/447 (0.4%) | 2 | 0/437 (0%) | 0 |
Disturbance In Attention | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Renal and urinary disorders | ||||||
Nephrolithiasis | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Reproductive system and breast disorders | ||||||
Hydrosalpinx | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||
Chronic Obstructive Pulmonary Disease | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Laryngeal Inflammation | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Skin and subcutaneous tissue disorders | ||||||
Dermal Cyst | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Vascular disorders | ||||||
Deep Vein Thrombosis | 0/319 (0%) | 0 | 0/447 (0%) | 0 | 1/437 (0.2%) | 1 |
Hypertension | 0/319 (0%) | 0 | 1/447 (0.2%) | 1 | 0/437 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
Placebo | Lemborexant 5 mg | Lemborexant 10 mg | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 75/319 (23.5%) | 129/447 (28.9%) | 140/437 (32%) | |||
Infections and infestations | ||||||
Influenza | 15/319 (4.7%) | 15 | 22/447 (4.9%) | 22 | 26/437 (5.9%) | 29 |
Nasopharyngitis | 40/319 (12.5%) | 43 | 51/447 (11.4%) | 67 | 48/437 (11%) | 56 |
Nervous system disorders | ||||||
Headache | 21/319 (6.6%) | 33 | 43/447 (9.6%) | 76 | 32/437 (7.3%) | 41 |
Somnolence | 5/319 (1.6%) | 5 | 38/447 (8.5%) | 44 | 60/437 (13.7%) | 64 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Eisai Medical Information |
---|---|
Organization | Eisai, Inc. |
Phone | +1-888-274-2378 |
esi_medinfo@eisai.com |
- E2006-G000-303
- 2015-001463-39