Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02952820
Recruitment Status : Completed
First Posted : November 2, 2016
Results First Posted : January 21, 2020
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Insomnia Disorder
Interventions Drug: lemborexant
Drug: Placebo
Enrollment 971
Recruitment Details Participants took part in the study at 119 investigative sites in Japan, Korea, Finland, Germany, Italy, New Zealand, Poland, Romania, Spain, Canada, Mexico, and the United States from 15 November 2016 to 08 January 2019.
Pre-assignment Details A total of 2059 participants were screened, of which 1088 were screen failures and 971 participants were randomized to receive study treatment.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide 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
Reason Not Completed
Adverse Event             8             9             16
Lost to Follow-up             7             7             6
Subject choice             15             12             17
Inadequate therapeutic effect             17             12             11
Other than specified             0             14             13
Withdrawal of consent             13             11             21
Not treated             4             4             4
Period Title: Active Treatment Period (6 Months)
Started 0 [1] 384 352
Completed 0 346 321
Not Completed 0 38 31
Reason Not Completed
Adverse Event             0             6             5
Lost to Follow-up             0             4             6
Subject choice             0             10             7
Inadequate therapeutic effect             0             6             2
Withdrawal of consent             0             6             8
Other than specified             0             6             2
Not treated             0             0             1
[1]
Participants from Placebo were re-randomized to Lemborexant 5 mg and Lemborexant 10 mg.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg Total
Hide 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 Number of Baseline Participants 318 316 315 949
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 318 participants 316 participants 315 participants 949 participants
54.5  (14.01) 54.2  (13.74) 54.8  (13.68) 54.5  (13.80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 318 participants 316 participants 315 participants 949 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 318 participants 316 participants 315 participants 949 participants
Hispanic or Latino
34
  10.7%
19
   6.0%
19
   6.0%
72
   7.6%
Not Hispanic or Latino
284
  89.3%
297
  94.0%
296
  94.0%
877
  92.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 318 participants 316 participants 315 participants 949 participants
White
232
  73.0%
222
  70.3%
225
  71.4%
679
  71.5%
Black or African American
23
   7.2%
27
   8.5%
26
   8.3%
76
   8.0%
Japanese
54
  17.0%
53
  16.8%
54
  17.1%
161
  17.0%
Chinese
0
   0.0%
3
   0.9%
1
   0.3%
4
   0.4%
Other Asian
5
   1.6%
5
   1.6%
3
   1.0%
13
   1.4%
American Indian or Alaska Native
0
   0.0%
1
   0.3%
2
   0.6%
3
   0.3%
Native Hawaiian or other Pacific Islander
0
   0.0%
1
   0.3%
0
   0.0%
1
   0.1%
Other
4
   1.3%
4
   1.3%
4
   1.3%
12
   1.3%
1.Primary Outcome
Title Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 316 participants 314 participants 312 participants
64.03  (45.209) 62.19  (45.674) 64.97  (44.020)
Change at Month 6 Number Analyzed 249 participants 245 participants 229 participants
-16.57  (35.313) -29.39  (33.261) -32.49  (35.962)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.701
Confidence Interval (2-Sided) 95%
0.607 to 0.810
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 316 participants 314 participants 312 participants
64.03  (45.209) 62.19  (45.674) 64.97  (44.020)
Change at 1st 7 nights Number Analyzed 314 participants 310 participants 310 participants
-4.11  (27.671) -16.86  (27.784) -18.89  (31.003)
Change at Month 1 Number Analyzed 299 participants 298 participants 297 participants
-11.48  (32.726) -19.41  (32.221) -24.06  (35.234)
Change at Month 3 Number Analyzed 279 participants 268 participants 264 participants
-13.84  (35.277) -25.08  (34.081) -27.94  (39.192)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.781
Confidence Interval (2-Sided) 95%
0.725 to 0.842
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.752
Confidence Interval (2-Sided) 95%
0.698 to 0.811
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.810
Confidence Interval (2-Sided) 95%
0.735 to 0.893
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.770
Confidence Interval (2-Sided) 95%
0.698 to 0.848
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.778
Confidence Interval (2-Sided) 95%
0.690 to 0.878
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM ratio
Estimated Value 0.770
Confidence Interval (2-Sided) 95%
0.681 to 0.869
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: percentage of sTST
Baseline Number Analyzed 307 participants 302 participants 299 participants
61.34  (17.836) 63.14  (18.231) 62.03  (17.248)
Change at 1st 7 nights Number Analyzed 303 participants 295 participants 296 participants
2.68  (10.765) 6.61  (10.386) 8.27  (10.566)
Change at Month 1 Number Analyzed 291 participants 284 participants 282 participants
6.11  (12.876) 7.87  (12.263) 9.92  (12.922)
Change at Month 3 Number Analyzed 269 participants 256 participants 251 participants
9.16  (13.644) 13.03  (13.522) 13.61  (14.035)
Change at Month 6 Number Analyzed 242 participants 235 participants 220 participants
10.36  (13.799) 15.34  (14.613) 15.55  (15.617)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0230
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 314 participants 313 participants 311 participants
132.49  (80.198) 132.77  (82.518) 136.83  (87.391)
Change at first 7 nights Number Analyzed 312 participants 308 participants 309 participants
-6.12  (45.893) -20.21  (46.015) -23.30  (47.700)
Change at Month 1 Number Analyzed 297 participants 297 participants 293 participants
-19.01  (50.279) -23.42  (56.251) -26.82  (56.989)
Change at Month 3 Number Analyzed 278 participants 267 participants 262 participants
-27.08  (54.408) -42.98  (60.064) -39.42  (62.783)
Change at Month 6 Number Analyzed 248 participants 244 participants 227 participants
-32.14  (55.279) -51.45  (67.295) -48.12  (68.550)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.1796
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0898
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0277
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0105
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 307 participants 302 participants 299 participants
304.25  (91.459) 315.52  (93.498) 306.89  (88.031)
Change at first 7 nights Number Analyzed 303 participants 295 participants 296 participants
14.78  (54.995) 34.29  (54.142) 46.01  (55.110)
Change at Month 1 Number Analyzed 291 participants 284 participants 282 participants
30.74  (70.687) 39.32  (63.548) 53.22  (67.910)
Change at Month 3 Number Analyzed 269 participants 256 participants 251 participants
48.16  (75.859) 65.82  (71.331) 70.95  (70.913)
Change at Month 6 Number Analyzed 242 participants 235 participants 220 participants
53.53  (74.539) 76.21  (77.714) 78.32  (80.741)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0259
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
6.Secondary Outcome
Title Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Measure Type: Number
Unit of Measure: percentage of responders
Sleep Onset Responders Number Analyzed 254 participants 250 participants 249 participants
17.7 31.2 30.1
Sleep Maintenance Responders Number Analyzed 250 participants 263 participants 257 participants
20.4 35.0 30.0
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of percentage
Estimated Value 13.67
Confidence Interval (2-Sided) 95%
6.24 to 21.10
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of percentage
Estimated Value 12.53
Confidence Interval (2-Sided) 95%
5.20 to 19.86
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of percentage
Estimated Value 14.65
Confidence Interval (2-Sided) 95%
6.97 to 22.33
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0110
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of percentage
Estimated Value 9.82
Confidence Interval (2-Sided) 95%
2.29 to 17.35
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Measure Type: Number
Unit of Measure: percentage of participants
Sleep Onset Responders Number Analyzed 310 participants 285 participants
34.2 37.2
Sleep Maintainance Responders Number Analyzed 317 participants 280 participants
35.0 39.6
8.Secondary Outcome
Title Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 318 participants 316 participants 315 participants
11.0  (2.10) 11.4  (2.02) 11.0  (2.15)
Change at Month 1 Number Analyzed 296 participants 300 participants 286 participants
-3.1  (3.41) -4.1  (3.66) -4.2  (4.01)
Change at Month 3 Number Analyzed 283 participants 274 participants 259 participants
-3.7  (3.55) -5.2  (3.88) -5.2  (4.05)
Change at Month 6 Number Analyzed 257 participants 258 participants 234 participants
-4.3  (3.66) -6.0  (3.76) -5.7  (4.00)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0137
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 318 participants 316 participants 315 participants
35.2  (13.55) 37.4  (12.74) 36.0  (13.01)
Change at Month 1 Number Analyzed 296 participants 300 participants 286 participants
-3.9  (11.62) -6.6  (11.83) -6.4  (13.68)
Change at Month 3 Number Analyzed 283 participants 274 participants 259 participants
-4.3  (11.37) -7.7  (12.97) -7.9  (13.56)
Change at Month 6 Number Analyzed 257 participants 258 participants 234 participants
-6.3  (12.07) -10.1  (13.56) -8.9  (14.91)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0670
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0257
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0206
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0134
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0128
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 318 316 315
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 316 participants 314 participants 312 participants
3.94  (1.558) 3.93  (1.349) 3.93  (1.324)
Change at First 7 nights Number Analyzed 314 participants 310 participants 310 participants
0.15  (0.991) 0.36  (0.964) 0.33  (1.018)
Change at Month 1 Number Analyzed 300 participants 298 participants 297 participants
0.44  (1.233) 0.53  (1.172) 0.55  (1.298)
Change at Month 3 Number Analyzed 280 participants 268 participants 264 participants
0.62  (1.366) 0.74  (1.325) 0.90  (1.452)
Change at Month 6 Number Analyzed 249 participants 245 participants 229 participants
0.79  (1.392) 0.98  (1.463) 1.05  (1.524)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0237
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4120
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4347
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4992
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0208
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.2248
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0298
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
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)
Hide Description [Not Specified]
Time Frame Baseline, First 7 nights (approximately Week 1) in active treatment period
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 442 participants 434 participants
4.15  (1.516) 4.16  (1.428)
Change at First 7 nights Number Analyzed 310 participants 310 participants
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Mean (Standard Deviation)
Unit of Measure: score on a scale
Screening Number Analyzed 440 participants 436 participants
3.63  (1.393) 3.54  (1.197)
Change at First 7 mornings Number Analyzed 335 participants 328 participants
1.03  (1.615) 1.32  (1.611)
Change at Second 7 mornings Number Analyzed 327 participants 313 participants
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 442 participants 434 participants
4.15  (1.516) 4.16  (1.428)
Change at Month 1 of exposure Number Analyzed 415 participants 412 participants
0.46  (1.082) 0.42  (1.223)
Change at Month 3 of exposure Number Analyzed 386 participants 375 participants
0.60  (1.264) 0.70  (1.356)
Change at Month 6 of exposure Number Analyzed 352 participants 331 participants
0.78  (1.424) 0.86  (1.461)
Change at Month 9 of exposure Number Analyzed 233 participants 213 participants
1.00  (1.512) 1.08  (1.489)
Change at Month 12 of exposure Number Analyzed 216 participants 204 participants
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Mean (Standard Deviation)
Unit of Measure: minutes
Mean of first 3 nights Number Analyzed 287 participants 284 participants
40.35  (48.661) 41.73  (55.694)
Mean sSOL of the first 7 nights Number Analyzed 337 participants 328 participants
41.35  (38.967) 41.90  (47.826)
Mean sSOL of the second 7 nights Number Analyzed 329 participants 312 participants
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Mean (Standard Deviation)
Unit of Measure: minutes
Mean of first 3 nights Number Analyzed 282 participants 282 participants
86.66  (80.038) 97.88  (83.302)
Mean of the first 7 nights Number Analyzed 337 participants 326 participants
91.56  (81.738) 95.79  (79.784)
Mean of the Last 7 nights Number Analyzed 329 participants 312 participants
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Measure Type: Number
Unit of Measure: percentage of participants
Average of first 3 nights Number Analyzed 285 participants 284 participants
9.46 9.38
Average of first 7 nights Number Analyzed 335 participants 328 participants
11.94 10.53
Average of second 7 nights Number Analyzed 327 participants 312 participants
11.71 9.38
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Measure Type: Number
Unit of Measure: percentage of participants
Average of first 3 nights Number Analyzed 280 participants 282 participants
11.26 12.59
Average of first 7 nights Number Analyzed 335 participants 325 participants
12.39 14.19
Average of second 7 nights Number Analyzed 327 participants 311 participants
13.51 11.90
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
sSOL: Change at Month 1 of exposure Number Analyzed 415 participants 412 participants
-17.17
(-19.76 to -14.58)
-18.64
(-21.26 to -16.02)
sSOL: Change at Month 3 of exposure Number Analyzed 386 participants 375 participants
-21.47
(-24.46 to -18.48)
-21.58
(-24.61 to -18.54)
sSOL: Change at Month 6 of exposure Number Analyzed 352 participants 331 participants
-24.13
(-27.22 to -21.04)
-22.99
(-26.14 to -19.83)
sSOL: Change at Month 9 of exposure Number Analyzed 233 participants 213 participants
-26.00
(-29.25 to -22.75)
-27.36
(-30.70 to -24.01)
sSOL: Change at Month 12 of exposure Number Analyzed 216 participants 214 participants
-25.83
(-29.44 to -22.22)
-26.32
(-30.03 to -22.61)
sWASO: Change at Month 1 of exposure Number Analyzed 414 participants 408 participants
-17.26
(-22.54 to -11.97)
-18.69
(-24.05 to -13.33)
sWASO: Change at Month 3 of exposure Number Analyzed 385 participants 373 participants
-31.34
(-37.12 to -25.57)
-28.97
(-34.86 to -23.09)
sWASO: Change at Month 6 of exposure Number Analyzed 351 participants 329 participants
-36.10
(-42.57 to -29.63)
-31.54
(-38.16 to -24.91)
sWASO: Change at Month 9 of exposure Number Analyzed 232 participants 212 participants
-39.28
(-46.74 to -31.83)
-40.39
(-48.08 to -32.71)
sWASO: Change at Month 12 of exposure Number Analyzed 215 participants 203 participants
-42.87
(-50.13 to -35.61)
-43.76
(-51.21 to -36.31)
sTST: Change at Month 1 of exposure Number Analyzed 400 participants 396 participants
31.98
(25.54 to 38.42)
38.04
(31.51 to 44.57)
sTST: Change at Month 3 of exposure Number Analyzed 373 participants 361 participants
49.27
(42.33 to 56.22)
53.51
(46.42 to 60.61)
sTST: Change at Month 6 of exposure Number Analyzed 342 participants 321 participants
54.99
(47.18 to 62.80)
56.36
(48.35 to 64.36)
sTST: Change at Month 9 of exposure Number Analyzed 222 participants 205 participants
55.41
(46.49 to 64.33)
61.13
(51.93 to 70.32)
sTST: Change at Month 12 of exposure Number Analyzed 207 participants 196 participants
58.15
(49.29 to 67.01)
66.50
(57.41 to 75.60)
19.Secondary Outcome
Title Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of sTST
Change at Month 1 of exposure Number Analyzed 400 participants 396 participants
6.35
(5.13 to 7.57)
7.32
(6.09 to 8.56)
Change at Month 3 of exposure Number Analyzed 373 participants 361 participants
10.01
(8.69 to 11.34)
10.25
(8.90 to 11.60)
Change at Month 6 of exposure Number Analyzed 342 participants 321 participants
11.10
(9.61 to 12.58)
11.08
(9.56 to 12.60)
Change at Month 9 of exposure Number Analyzed 222 participants 205 participants
11.85
(10.13 to 13.56)
12.84
(11.08 to 14.61)
Change at Month 12 of exposure Number Analyzed 207 participants 196 participants
12.61
(10.92 to 14.31)
13.66
(11.92 to 15.40)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
sSOL: Change at Month 7 of exposure Number Analyzed 355 participants 334 participants
-28.55
(-32.39 to -24.70)
-29.46
(-33.42 to -25.50)
sSOL: Change at Month 9 of exposure Number Analyzed 349 participants 324 participants
-32.10
(-35.39 to -28.80)
-30.91
(-34.31 to -27.52)
sSOL: Change at Month 12 of exposure Number Analyzed 323 participants 306 participants
-31.40
(-34.85 to -27.96)
-31.33
(-34.88 to -27.78)
sWASO: Change at Month 7 of exposure Number Analyzed 355 participants 334 participants
-45.62
(-52.53 to -38.70)
-43.09
(-50.20 to -35.99)
sWASO: Change at Month 9 of exposure Number Analyzed 349 participants 324 participants
-47.70
(-54.54 to -40.86)
-48.87
(-55.92 to -41.82)
sWASO: Change at Month 12 of exposure Number Analyzed 323 participants 306 participants
-48.46
(-55.35 to -41.57)
-49.28
(-56.36 to -42.19)
sTST: Change at Month 7 of exposure Number Analyzed 355 participants 334 participants
75.00
(65.30 to 84.71)
76.95
(66.97 to 86.92)
sTST: Change at Month 9 of exposure Number Analyzed 349 participants 324 participants
78.69
(68.99 to 88.39)
81.24
(71.26 to 91.23)
sTST: Change at Month 12 of exposure Number Analyzed 323 participants 306 participants
78.61
(68.61 to 88.61)
83.61
(73.33 to 93.90)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of sTST
Change at Month 7 of exposure Number Analyzed 354 participants 334 participants
12.88
(9.01 to 16.75)
15.12
(11.13 to 19.10)
Change at Month 9 of exposure Number Analyzed 349 participants 324 participants
16.54
(14.88 to 18.20)
16.49
(14.78 to 18.20)
Change at Month 12 of exposure Number Analyzed 323 participants 306 participants
16.34
(14.70 to 17.98)
16.82
(15.13 to 18.50)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
sSOL: Change at Month 1 of exposure Number Analyzed 415 participants 412 participants
-17.17
(-19.76 to -14.58)
-18.64
(-21.26 to -16.02)
sSOL: Change at Month 3 of exposure Number Analyzed 386 participants 375 participants
-21.47
(-24.46 to -18.48)
-21.58
(-24.61 to -18.54)
sSOL: Change at Month 6 of exposure Number Analyzed 352 participants 331 participants
-24.13
(-27.22 to -21.04)
-22.99
(-26.14 to -19.83)
sWASO: Change at Month 1 of exposure Number Analyzed 414 participants 408 participants
-17.26
(-22.54 to -11.97)
-18.69
(-24.05 to -13.33)
sWASO: Change at Month 3 of exposure Number Analyzed 385 participants 373 participants
-31.34
(-37.12 to -25.57)
-28.97
(-34.86 to -23.09)
sWASO: Change at Month 6 of exposure Number Analyzed 351 participants 329 participants
-36.10
(-42.57 to -29.63)
-31.54
(-38.16 to -24.91)
sTST: Change at Month 1 of exposure Number Analyzed 400 participants 396 participants
31.98
(25.54 to 38.42)
38.04
(31.51 to 44.57)
sTST: Change at Month 3 of exposure Number Analyzed 373 participants 361 participants
49.27
(42.33 to 56.22)
53.51
(46.42 to 60.61)
sTST: Change at Month 6 of exposure Number Analyzed 342 participants 321 participants
54.99
(47.18 to 62.80)
56.36
(48.35 to 64.36)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 444 437
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of sTST
Change at Month 1 of exposure Number Analyzed 400 participants 396 participants
6.35
(5.13 to 7.57)
7.32
(6.09 to 8.56)
Change at Month 3 of exposure Number Analyzed 373 participants 361 participants
10.01
(8.69 to 11.34)
10.25
(8.90 to 11.60)
Change at Month 6 of exposure Number Analyzed 342 participants 321 participants
11.10
(9.61 to 12.58)
11.08
(9.56 to 12.60)
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/319 (0.00%)      0/447 (0.00%)      0/437 (0.00%)    
Hide 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 (1.57%)      18/447 (4.03%)      16/437 (3.66%)    
Cardiac disorders       
Angina Pectoris  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Acute myocardial infarction  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Atrial fibrillation  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Extrasystoles  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Endocrine disorders       
Goitre  1  1/319 (0.31%)  1 0/447 (0.00%)  0 0/437 (0.00%)  0
Eye disorders       
Diabetic Retinopathy  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Floppy eyelid syndrome  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Gastrointestinal disorders       
Alcoholic pancreatitis  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Gastrointestinal haemorrhage  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Gastrointestinal inflammation  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Hiatus hernia  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
General disorders       
Chest Pain  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Cyst  1  1/319 (0.31%)  1 0/447 (0.00%)  0 0/437 (0.00%)  0
Inflammation  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Non-cardiac chest pain  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Hepatobiliary disorders       
Cholestasis  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Hepatotoxicity  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Infections and infestations       
Cystitis  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Pneumonia  1  1/319 (0.31%)  1 1/447 (0.22%)  1 0/437 (0.00%)  0
Postoperative Wound Infection  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Erysipelas  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Injury, poisoning and procedural complications       
Fall  1  0/319 (0.00%)  0 1/447 (0.22%)  1 1/437 (0.23%)  1
Lower Limb Fracture  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Pelvic Fracture  1  1/319 (0.31%)  1 0/447 (0.00%)  0 0/437 (0.00%)  0
Rib Fracture  1  1/319 (0.31%)  1 0/447 (0.00%)  0 1/437 (0.23%)  1
Tibia Fracture  1  1/319 (0.31%)  1 0/447 (0.00%)  0 0/437 (0.00%)  0
Ankle fracture  1  0/319 (0.00%)  0 1/447 (0.22%)  1 1/437 (0.23%)  1
Hand fracture  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Meniscus injury  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Intentional Overdose  1  0/319 (0.00%)  0 1/447 (0.22%)  7 0/437 (0.00%)  0
Metabolism and nutrition disorders       
Type 2 Diabetes Mellitus  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Musculoskeletal and connective tissue disorders       
Jaw Cyst  1  1/319 (0.31%)  1 0/447 (0.00%)  0 0/437 (0.00%)  0
Jaw Fistula  1  1/319 (0.31%)  1 0/447 (0.00%)  0 0/437 (0.00%)  0
Osteoarthritis  1  0/319 (0.00%)  0 1/447 (0.22%)  1 3/437 (0.69%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Intraductal Proliferative Breast Lesion  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Breast cancer  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Nervous system disorders       
Cerebrovascular Accident  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Diabetic Neuropathy  1  0/319 (0.00%)  0 2/447 (0.45%)  2 0/437 (0.00%)  0
Disturbance In Attention  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Renal and urinary disorders       
Nephrolithiasis  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Reproductive system and breast disorders       
Hydrosalpinx  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Chronic Obstructive Pulmonary Disease  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Laryngeal Inflammation  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Skin and subcutaneous tissue disorders       
Dermal Cyst  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
Vascular disorders       
Deep Vein Thrombosis  1  0/319 (0.00%)  0 0/447 (0.00%)  0 1/437 (0.23%)  1
Hypertension  1  0/319 (0.00%)  0 1/447 (0.22%)  1 0/437 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Lemborexant 5 mg Lemborexant 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   75/319 (23.51%)      129/447 (28.86%)      140/437 (32.04%)    
Infections and infestations       
Influenza  1  15/319 (4.70%)  15 22/447 (4.92%)  22 26/437 (5.95%)  29
Nasopharyngitis  1  40/319 (12.54%)  43 51/447 (11.41%)  67 48/437 (10.98%)  56
Nervous system disorders       
Headache  1  21/319 (6.58%)  33 43/447 (9.62%)  76 32/437 (7.32%)  41
Somnolence  1  5/319 (1.57%)  5 38/447 (8.50%)  44 60/437 (13.73%)  64
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Information
Organization: Eisai, Inc.
Phone: +1-888-274-2378
EMail: esi_medinfo@eisai.com
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02952820    
Other Study ID Numbers: E2006-G000-303
2015-001463-39 ( EudraCT Number )
First Submitted: October 31, 2016
First Posted: November 2, 2016
Results First Submitted: January 8, 2020
Results First Posted: January 21, 2020
Last Update Posted: February 6, 2020