Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)

Sponsor
Eisai Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02952820
Collaborator
(none)
971
114
3
25.8
8.5
0.3

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

Study Type:
Interventional
Actual Enrollment :
971 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Long-Term Multicenter, Randomized, Double-Blind, Controlled, Parallel Group Study of the Safety and Efficacy of Lemborexant in Subjects With Insomnia Disorder (SUNRISE 2)
Actual Study Start Date :
Nov 15, 2016
Actual Primary Completion Date :
Jan 8, 2019
Actual Study Completion Date :
Jan 8, 2019

Arms and Interventions

Arm Intervention/Treatment
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

  1. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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]

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Male or female, age 18 years or older at the time of informed consent

  • Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria for Insomnia Disorder, as follows:

  • Complains of dissatisfaction with nighttime sleep in the form of difficulty getting to sleep, difficulty staying asleep, and/or awakening earlier in the morning than desired despite adequate opportunity for sleep

  • Frequency of complaint ≥3 times per week

  • Duration of complaint ≥3 months

  • Associated with complaint of daytime impairment

  • History of (Subjective Sleep Onset Latency) sSOL ≥30 minutes on at least 3 nights per week in the previous 4 weeks and/or subjective Wake after Sleep Onset (sWASO) ≥60 minutes on at least 3 nights per week in the previous 4 weeks

  • History of regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours

  • Regular bedtime, between 21:00 and 01:00 and regular wake time, the time the participant gets out of bed for the day, between 05:00 and 10:00

  • Insomnia Severity Index (ISI) score ≥15

  • Confirmation of current insomnia symptoms as determined from the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL ≥30 minutes on at least 3 of the 7 nights and/or sWASO ≥60 minutes on at least 3 of the 7 nights

  • Confirmation of time spent in bed, as determined from on the Sleep Diary completed on 7 mornings between the first and second screening visit, such that there are not more than 2 nights with duration of time spent in bed 7 hours and 10 hours

  • Confirmation of regular bedtimes and wake times such that the participant has a regular time spent in bed, either sleeping or trying to sleep, between 7 and 10 hours for the final 7 nights of the before visit 3.

  • Confirmation of regular bedtime between 21:00 and 01:00 and time of getting out of bed for the day between 05:00 and 10:00 for the final 7 nights of the before visit 3.

  • Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night

  • Willing to not start a behavioral or other treatment program for insomnia during the participants participation in the study

Exclusion Criteria:
  • A current diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia.

  • STOPBang score greater than or equal to (>=) 5

  • International Restless Legs Scale (IRLS) score >=16

  • Epworth Sleepiness Scale (ESS) score >15

  • Reports symptoms potentially related to narcolepsy that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy

  • Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior, eg, making phone calls, or preparing and eating food while asleep

  • For participants who underwent polysomnography (PSG) within the previous year:

  • Age 18 to 64 years: Apnea Hypopnea Index ≥10, or Periodic Limb Movements with Arousal Index ≥10

  • Age ≥65 years: Apnea Hypopnea Index >15, or Periodic Limb Movements with Arousal Index >15

  • Beck Depression Inventory - II (BDI II) score >19 at Screening

  • Beck Anxiety Inventory (BAI) score >15 at Screening

  • Habitually naps more than 3 times per week

  • Females who are breastfeeding or pregnant at Screening or Study Baseline

  • Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.)

  • Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or habitually consumes caffeine-containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study

  • History of drug or alcohol dependency or abuse within approximately the previous 2 years

  • Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males), or unwilling to limit alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3 hours before bedtime for the duration of his/her participation in the study

  • A prolonged QT/QT interval corrected by Fridericia's formula (QTcF >450 ms) as demonstrated by a repeated electro cardiogram(ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms)

  • Current evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, neurological [including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation], or psychiatric disease or malignancy other than basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments

  • Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night

  • Scheduled for major surgery during the study

  • Used any prohibited prescription or over-the-counter concomitant medications within 1 week before the first dose of study medication

  • Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks before Screening

  • Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator

  • Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Study Baseline

  • Previously participated in any clinical trial of lemborexant

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.
Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT02952820
Other Study ID Numbers:
  • E2006-G000-303
  • 2015-001463-39
First Posted:
Nov 2, 2016
Last Update Posted:
Feb 6, 2020
Last Verified:
Dec 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Eisai Inc.
Additional relevant MeSH terms:

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.
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

1. Primary Outcome
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
2. Secondary Outcome
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
3. Secondary Outcome
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
4. Secondary Outcome
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
5. Secondary Outcome
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
6. Secondary Outcome
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
7. Secondary Outcome
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%
8. Secondary Outcome
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
9. Secondary Outcome
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
10. Secondary Outcome
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
11. Secondary Outcome
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)
12. Secondary Outcome
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)
13. Secondary Outcome
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)
14. Secondary Outcome
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)
15. Secondary Outcome
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)
16. Secondary Outcome
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%
17. Secondary Outcome
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%
18. Secondary Outcome
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
19. Secondary Outcome
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
20. Secondary Outcome
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
21. Secondary Outcome
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
22. Secondary Outcome
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
23. Secondary Outcome
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

[Not Specified]

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
Email esi_medinfo@eisai.com
Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT02952820
Other Study ID Numbers:
  • E2006-G000-303
  • 2015-001463-39
First Posted:
Nov 2, 2016
Last Update Posted:
Feb 6, 2020
Last Verified:
Dec 1, 2017