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Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) (SUNRISE 1)

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: NCT02783729
Recruitment Status : Completed
First Posted : May 26, 2016
Results First Posted : February 11, 2020
Last Update Posted : February 11, 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
Interventions Drug: Lemborexant
Drug: Lemborexant-matched placebo
Drug: Zolpidem tartrate
Drug: Zolpidem-matched placebo
Enrollment 1006
Recruitment Details Participants took part in the study at 67 investigative sites in the United States, Spain, Germany, Canada, United Kingdom, and Italy from 31 May 2016 to 30 January 2018.
Pre-assignment Details A total of 3537 participants were screened, of which 1006 participants were randomized to the treatment period. All participants who were subsequently randomized completed a Run-in Period before randomization to treatment period.
Arm/Group Title Placebo Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. Participants received zolpidem tartrate extended release (ZOL ER) 6.25 milligram (mg) and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period. Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Period Title: Overall Study
Started 208 263 266 269
Completed 198 246 258 260
Not Completed 10 17 8 9
Reason Not Completed
Lack of Efficacy             1             0             0             0
Adverse Event             2             6             2             3
Other             1             6             2             3
Withdrawal by Subject             2             3             1             2
Participant's choice             2             1             2             1
Lost to Follow-up             2             1             1             0
Arm/Group Title Placebo Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg Total
Hide Arm/Group Description Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. Participants received zolpidem tartrate extended release (ZOL ER) 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period. Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period. Total of all reporting groups
Overall Number of Baseline Participants 208 263 266 269 1006
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 208 participants 263 participants 266 participants 269 participants 1006 participants
63.4  (6.36) 64.3  (7.12) 63.7  (6.78) 64.2  (6.88) 63.9  (6.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 263 participants 266 participants 269 participants 1006 participants
Female
184
  88.5%
226
  85.9%
229
  86.1%
230
  85.5%
869
  86.4%
Male
24
  11.5%
37
  14.1%
37
  13.9%
39
  14.5%
137
  13.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 263 participants 266 participants 269 participants 1006 participants
Hispanic or Latino
35
  16.8%
32
  12.2%
51
  19.2%
47
  17.5%
165
  16.4%
Not Hispanic or Latino
173
  83.2%
231
  87.8%
215
  80.8%
222
  82.5%
841
  83.6%
Unknown or Not Reported
0
   0.0%
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 208 participants 263 participants 266 participants 269 participants 1006 participants
White
153
  73.6%
173
  65.8%
199
  74.8%
202
  75.1%
727
  72.3%
Black or African American
51
  24.5%
80
  30.4%
63
  23.7%
62
  23.0%
256
  25.4%
Japanese
1
   0.5%
1
   0.4%
0
   0.0%
0
   0.0%
2
   0.2%
Chinese
1
   0.5%
0
   0.0%
0
   0.0%
1
   0.4%
2
   0.2%
Other Asian
0
   0.0%
4
   1.5%
2
   0.8%
4
   1.5%
10
   1.0%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific
0
   0.0%
2
   0.8%
0
   0.0%
0
   0.0%
2
   0.2%
Other
2
   1.0%
3
   1.1%
2
   0.8%
0
   0.0%
7
   0.7%
1.Primary Outcome
Title Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
Hide Description LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by PSG. Change from baseline to average LPS on Day 29 and 30 was reported.
Time Frame Baseline, Days 29/30
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 266 269
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 208 participants 266 participants 269 participants
43.89  (33.596) 44.86  (36.528) 44.61  (32.986)
Change at Days 29/30 Number Analyzed 200 participants 260 participants 260 participants
-7.93  (31.946) -19.53  (33.054) -21.46  (32.436)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0003
Comments Based on mixed effect model repeated measurement (MMRM) model with log transformation of LPS and factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Geometric Mean(LSGM) Ratio
Estimated Value 0.773
Confidence Interval (2-Sided) 95%
0.672 to 0.889
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with log transformation of LPS and factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSGM Ratio
Estimated Value 0.723
Confidence Interval (2-Sided) 95%
0.628 to 0.832
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
Hide Description SE is defined as percentage of time spent in bed asleep, calculated as total sleep time (TST) divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 29 and 30 was reported.
Time Frame Baseline, Days 29/30
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 266 269
Mean (Standard Deviation)
Unit of Measure: Percentage of time in bed asleep
Baseline Number Analyzed 208 participants 266 participants 269 participants
68.89  (9.639) 68.36  (11.268) 67.85  (10.849)
Change at Days 29/30 Number Analyzed 200 participants 260 participants 260 participants
5.35  (9.897) 12.93  (9.741) 14.09  (10.514)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline SE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean (LSM) Difference
Estimated Value 7.07
Confidence Interval (2-Sided) 95%
5.61 to 8.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.746
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline SE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 8.03
Confidence Interval (2-Sided) 95%
6.57 to 9.49
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.746
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
Hide Description WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. Change from baseline to average WASO on Days 29 and 30 was reported.
Time Frame Baseline, Days 29/30
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 266 269
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 208 participants 266 participants 269 participants
111.75  (37.179) 113.44  (38.953) 114.83  (39.997)
Change at Days 29/30 Number Analyzed 200 participants 260 participants 260 participants
-18.58  (41.931) -43.89  (39.264) -46.43  (39.595)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline WASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -23.96
Confidence Interval (2-Sided) 95%
-29.98 to -17.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.068
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -25.35
Confidence Interval (2-Sided) 95%
-31.36 to -19.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.067
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30
Hide Description WASO2H is defined as time in minutes of wake during the interval from 240 minutes after lights off until lights on as measured by PSG. Change from baseline to average WASO2H on Days 29 and 30 was reported.
Time Frame Baseline, Days 29/30
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized Participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received zolpidem tartrate extended release (ZOL ER) 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 262 266 269
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 262 participants 266 participants 269 participants
78.04  (33.849) 76.60  (32.903) 76.88  (32.126)
Change at Days 29/30 Number Analyzed 250 participants 260 participants 260 participants
-21.42  (36.257) -27.19  (33.047) -28.84  (33.138)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline WASO2H as a covariate.
Statistical Test of Hypothesis P-Value = 0.0038
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -6.65
Confidence Interval (2-Sided) 95%
-11.15 to -2.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.298
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline WASO2H as a covariate.
Statistical Test of Hypothesis P-Value = 0.0005
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -8
Confidence Interval (2-Sided) 95%
-12.53 to -3.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.309
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3
Hide Description Body sway is detected through a cable around the participant's waist by the ataxia meter. Body sway is measured in units of one-third degree of the angle of arc. For ease in reporting, these are called arbitrary units, with a higher number indicating more body sway (less postural stability). Change from baseline in mean body sway on Days 2 and 3 was reported.
Time Frame Baseline, Days 2/3
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received zolpidem tartrate extended release (ZOL ER) 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 239 245 243
Mean (Standard Deviation)
Unit of Measure: one-third degree of angle of arc
Baseline Number Analyzed 239 participants 245 participants 243 participants
26.96  (26.502) 26.40  (20.781) 36.29  (197.282)
Change at Days 2/3 Number Analyzed 234 participants 237 participants 234 participants
8.47  (69.894) -0.82  (20.383) -8.97  (146.679)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments Zolpidem Tartrate Extended Release 6.25 mg v Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0171
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 2/3), and treatment-by-visit interaction as fixed effect, and the baseline posture stability of body sway as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -9.63
Confidence Interval (2-Sided) 95%
-17.53 to -1.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.029
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments Zolpidem Tartrate Extended Release 6.25 mg v Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.008
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 2/3), and treatment-by-visit interaction as fixed effect, and the baseline posture stability of body sway as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -10.74
Confidence Interval (2-Sided) 95%
-18.67 to -2.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.04
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30
Hide Description LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by the PSG. WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. TST is defined as the amount of sleep in minutes from LPS until terminal awakening as measured by PSG. Change from baseline to average LPS, WASO, and TST on Days 1 and 2, and Days 29 and 30 were reported.
Time Frame Baseline, Days 1/2, and Days 29/30
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received zolpidem tartrate extended release (ZOL ER) 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 262 266 269
Mean (Standard Deviation)
Unit of Measure: minutes
LPS: Baseline Number Analyzed 262 participants 266 participants 269 participants
44.52  (38.349) 44.86  (36.528) 44.61  (32.986)
LPS: Change at Days 1/2 Number Analyzed 262 participants 266 participants 269 participants
-12.56  (32.506) -16.59  (28.742) -19.48  (31.809)
LPS: Change at Days 29/30 Number Analyzed 250 participants 260 participants 260 participants
-7.51  (35.065) -19.53  (33.054) -21.46  (32.436)
WASO: Baseline Number Analyzed 262 participants 266 participants 269 participants
114.31  (39.992) 113.44  (38.953) 114.83  (39.997)
WASO: Change at Days 1/2 Number Analyzed 262 participants 266 participants 269 participants
-44.36  (38.074) -49.96  (39.578) -59.59  (37.749)
WASO: Change at Days 29/30 Number Analyzed 250 participants 260 participants 260 participants
-36.50  (43.406) -43.89  (39.264) -46.43  (39.595)
TST: Baseline Number Analyzed 262 participants 266 participants 269 participants
326.99  (54.852) 328.00  (54.224) 325.07  (52.819)
TST: Change at Days 1/2 Number Analyzed 262 participants 266 participants 269 participants
55.31  (48.138) 65.22  (46.695) 79.58  (47.350)
TST: Change at Days 29/30 Number Analyzed 250 participants 260 participants 260 participants
43.34  (54.012) 61.99  (46.817) 67.86  (52.117)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments LPS, Days 1/2: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0218
Comments Based on MMRM model with log transformation of LPS and factors for age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.874
Confidence Interval (2-Sided) 95%
0.78 to 0.981
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments LPS, Days 1/2: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0006
Comments Based on MMRM model with log transformation of LPS and factors for age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.818
Confidence Interval (2-Sided) 95%
0.729 to 0.917
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments LPS, Days 29/30: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with log transformation of LPS and factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.634
Confidence Interval (2-Sided) 95%
0.556 to 0.724
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments LPS, Days 29/30: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with log transformation of LPS and factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.594
Confidence Interval (2-Sided) 95%
0.521 to 0.677
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments WASO, Days 1/2: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0154
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline WASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -6.16
Confidence Interval (2-Sided) 95%
-11.15 to -1.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.544
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments WASO, Days 1/2: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline WASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -15.03
Confidence Interval (2-Sided) 95%
-20.01 to -10.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.542
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments WASO, Days 29/30: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0073
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline WASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -7.72
Confidence Interval (2-Sided) 95%
-13.36 to -2.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.876
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments WASO, Days 29/30: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0016
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -9.1
Confidence Interval (2-Sided) 95%
-14.75 to -3.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.883
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments TST, Days 1/2: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.001
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 10.25
Confidence Interval (2-Sided) 95%
4.18 to 16.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.094
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments TST, Days 1/2: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 23.1
Confidence Interval (2-Sided) 95%
17.04 to 29.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.085
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments TST, Days 29/30: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 19.41
Confidence Interval (2-Sided) 95%
12.63 to 26.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.457
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments TST, Days 29/30: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors for age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effects, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 24.1
Confidence Interval (2-Sided) 95%
17.32 to 30.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.456
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
Hide Description sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with diary handling rules (DHR) on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time Frame First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received zolpidem tartrate extended release (ZOL ER) 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 259 264 269
Mean (Standard Deviation)
Unit of Measure: minutes
sSOL: Baseline: With DHR Number Analyzed 258 participants 263 participants 269 participants
60.54  (36.350) 65.79  (43.530) 60.88  (42.514)
sSOL: 1st 7 nights: With DHR Number Analyzed 251 participants 259 participants 266 participants
-16.23  (29.531) -22.54  (32.812) -21.88  (29.269)
sSOL: last 7 nights: With DHR Number Analyzed 246 participants 252 participants 258 participants
-17.04  (30.683) -25.20  (34.854) -24.79  (34.068)
sWASO: Baseline: With DHR Number Analyzed 259 participants 264 participants 266 participants
173.06  (77.212) 166.76  (82.047) 175.35  (83.453)
sWASO: Change at 1st 7 nights: With DHR Number Analyzed 253 participants 261 participants 262 participants
-48.91  (51.761) -39.33  (55.022) -55.06  (66.696)
sWASO: Change at last 7 nights: With DHR Number Analyzed 247 participants 253 participants 253 participants
-63.52  (64.161) -44.51  (58.090) -57.96  (72.791)
sTST: Baseline: With DHR Number Analyzed 247 participants 253 participants 258 participants
273.07  (81.207) 275.74  (83.650) 266.10  (92.164)
sTST: Change at 1st 7 nights: With DHR Number Analyzed 240 participants 251 participants 254 participants
56.99  (62.880) 50.30  (60.065) 67.80  (71.134)
sTST: Change at last 7 nights: With DHR Number Analyzed 235 participants 245 participants 244 participants
71.01  (76.574) 62.41  (68.555) 79.95  (81.211)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sSOL, First 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0122
Comments Based on MMRM model model with log transformation of sSOL and factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.898
Confidence Interval (2-Sided) 95%
0.825 to 0.977
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sSOL, First 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model model with log transformation of sSOL and factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.763 to 0.902
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sSOL, Last 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0176
Comments Based on MMRM model model with log transformation of sSOL and factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.882
Confidence Interval (2-Sided) 95%
0.796 to 0.978
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sSOL, Last 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model model with log transformation of sSOL and with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.811
Confidence Interval (2-Sided) 95%
0.732 to 0.899
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sWASO, First 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0706
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 8.12
Confidence Interval (2-Sided) 95%
-0.68 to 16.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.484
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sWASO, First 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.1949
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.81
Confidence Interval (2-Sided) 95%
-14.61 to 2.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.481
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sWASO, Last 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0059
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 14.45
Confidence Interval (2-Sided) 95%
4.16 to 24.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.241
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sWASO, Last 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3064
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 5.36
Confidence Interval (2-Sided) 95%
-4.92 to 15.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.241
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sTST, First 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2174
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baselines sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -6.57
Confidence Interval (2-Sided) 95%
-17.02 to 3.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.325
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sTST, First 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0949
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 8.88
Confidence Interval (2-Sided) 95%
-1.55 to 19.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.313
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sTST, Last 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2718
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -6.82
Confidence Interval (2-Sided) 95%
-19.01 to 5.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.207
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sTST, Last 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2317
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.43
Confidence Interval (2-Sided) 95%
-4.75 to 19.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.206
Estimation Comments [Not Specified]
8.Other Pre-specified Outcome
Title Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
Hide Description sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time Frame First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received ZOL ER 6.25 mg and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 247 253 258
Mean (Standard Deviation)
Unit of Measure: % of subjective time in bed asleep
sSE: Baseline: With DHR Number Analyzed 247 participants 253 participants 258 participants
55.49  (15.802) 56.05  (17.094) 54.31  (18.318)
sSE: Change at 1st 7 nights: With DHR Number Analyzed 240 participants 251 participants 254 participants
11.96  (12.526) 10.56  (12.296) 13.97  (14.188)
sSE: Change at last 7 nights: With DHR Number Analyzed 235 participants 245 participants 244 participants
14.83  (15.011) 12.92  (13.884) 16.12  (16.300)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sSE, First 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.1963
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -1.37
Confidence Interval (2-Sided) 95%
-3.46 to 0.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.063
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sSE, First 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate
Statistical Test of Hypothesis P-Value = 0.1093
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-0.38 to 3.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sSE, Last 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2196
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -1.53
Confidence Interval (2-Sided) 95%
-3.98 to 0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.247
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sSE, Last 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.4013
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
-1.4 to 3.49
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.246
Estimation Comments [Not Specified]
9.Other Pre-specified Outcome
Title Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
Hide Description LPS: amount of time in minutes from lights off to first epoch of 20 consecutive epochs of non-wakefulness. WASO: amount of time in minutes of wake from the onset of persistent sleep until lights. WASO2H: amount of time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST: amount of time in minutes of sleep from sleep onset until terminal awakening. LPS, WASO, WASO2H, and TST were measured by PSG. Change from baseline to average LPS, WASO, WASO2H, and TST on Day 1 and 2 were reported.
Time Frame Baseline, Days 1/2
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 266 269
Mean (Standard Deviation)
Unit of Measure: minutes
LPS: Baseline 43.89  (33.596) 44.86  (36.528) 44.61  (32.986)
LPS: Change at Days 1/2 -6.45  (32.618) -16.59  (28.742) -19.48  (31.809)
WASO: Baseline 111.75  (37.179) 113.44  (38.953) 114.83  (39.997)
WASO: Change at Days 1/2 -15.07  (36.938) -49.96  (39.578) -59.59  (37.749)
WASO2H: Baseline 74.44  (30.109) 76.60  (32.903) 76.88  (32.126)
WASO2H: Change at Days 1/2 -7.06  (31.097) -30.28  (32.056) -37.10  (30.815)
TST: Baseline 330.67  (46.268) 328.00  (54.224) 325.07  (52.819)
TST: Change at Days 1/2 19.44  (43.348) 65.22  (46.695) 79.58  (47.350)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments LPS: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0092
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.752 to 0.961
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments LPS: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0002
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days1/2), and treatment-by-visit interaction as fixed effects, and the baseline LPS as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.795
Confidence Interval (2-Sided) 95%
0.704 to 0.899
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments WASO: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effect, and the baseline WASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -33.4
Confidence Interval (2-Sided) 95%
-38.71 to -28.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.711
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments WASO: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effect, and the baseline WASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -42.27
Confidence Interval (2-Sided) 95%
-47.57 to -36.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.705
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments WASO2H: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline WASO2H as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -21.66
Confidence Interval (2-Sided) 95%
-26.01 to -17.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.221
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments WASO2H: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline WASO2H as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -28.33
Confidence Interval (2-Sided) 95%
-32.68 to -23.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.219
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments TST: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effect, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 44.05
Confidence Interval (2-Sided) 95%
37.59 to 50.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.291
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments TST: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effect, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 56.9
Confidence Interval (2-Sided) 95%
50.46 to 63.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.284
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
Hide Description SE is defined as percentage of time spent in bed asleep, calculated as TST divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 1 and 2 were reported.
Time Frame Baseline, Days 1/2
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 266 269
Mean (Standard Deviation)
Unit of Measure: Percentage of time in bed asleep
SE: Baseline 68.89  (9.639) 68.36  (11.268) 67.85  (10.849)
SE: Change at Days 1/2 4.22  (9.033) 13.60  (9.725) 16.48  (9.623)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments SE: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effects, and the baseline SE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 9.01
Confidence Interval (2-Sided) 95%
7.7 to 10.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.666
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments SE: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 1/2), and treatment-by-visit interaction as fixed effect, and the baseline SE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 11.6
Confidence Interval (2-Sided) 95%
10.3 to 12.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.664
Estimation Comments [Not Specified]
11.Other Pre-specified Outcome
Title Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
Hide Description WASO2H is defined as the time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST is defined as the amount of sleep in minutes from sleep onset until terminal awakening. WASO and TST were measured by PSG. Change from baseline to average WASO and TST on Day 29 and 30 were reported.
Time Frame Baseline, Days 29/30
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 266 269
Mean (Standard Deviation)
Unit of Measure: minutes
WASO2H: Baseline Number Analyzed 208 participants 266 participants 269 participants
74.44  (30.109) 76.60  (32.903) 76.88  (32.126)
WASO2H: Days 29 /30 Number Analyzed 200 participants 260 participants 260 participants
-8.92  (31.909) -27.19  (33.047) -28.84  (33.138)
TST: Baseline Number Analyzed 208 participants 266 participants 269 participants
330.67  (46.268) 328.00  (54.224) 325.07  (52.819)
TST: Days 29/30 Number Analyzed 200 participants 260 participants 260 participants
25.65  (47.587) 61.99  (46.817) 67.86  (52.117)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments WASO2H: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline WASO2H as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -16.41
Confidence Interval (2-Sided) 95%
-21.23 to -11.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.457
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments WASO2H: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline WASO2H as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -17.76
Confidence Interval (2-Sided) 95%
-22.57 to -12.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.451
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments TST: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 34.16
Confidence Interval (2-Sided) 95%
26.95 to 41.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.673
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments TST: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Days 29/30), and treatment-by-visit interaction as fixed effect, and the baseline TST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 38.85
Confidence Interval (2-Sided) 95%
31.64 to 46.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.672
Estimation Comments [Not Specified]
12.Other Pre-specified Outcome
Title Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
Hide Description sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time Frame First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 206 264 269
Mean (Standard Deviation)
Unit of Measure: minutes
sSOL: Baseline: With DHR Number Analyzed 206 participants 263 participants 269 participants
55.90  (37.389) 65.79  (43.530) 60.88  (42.514)
sSOL: Change at 1st 7 nights :With DHR Number Analyzed 202 participants 259 participants 266 participants
-6.83  (23.040) -22.54  (32.812) -21.88  (29.269)
sSOL: Change at last 7 nights: With DHR Number Analyzed 196 participants 252 participants 258 participants
-8.10  (27.447) -25.20  (34.854) -24.79  (34.068)
sWASO: Baseline: With DHR Number Analyzed 206 participants 264 participants 266 participants
170.89  (80.676) 166.76  (82.047) 175.35  (83.453)
sWASO: Change at 1st 7 nights: With DHR Number Analyzed 202 participants 261 participants 262 participants
-27.92  (45.201) -39.33  (55.022) -55.06  (66.696)
sWASO: Change at last 7 nights: With DHR Number Analyzed 196 participants 253 participants 253 participants
-36.01  (57.584) -44.51  (58.090) -57.96  (72.791)
sTST: Baseline: With DHR Number Analyzed 201 participants 253 participants 258 participants
276.23  (87.649) 275.74  (83.650) 266.10  (92.164)
sTST: Change at 1st 7 nights: With DHR Number Analyzed 197 participants 251 participants 254 participants
30.86  (57.437) 50.30  (60.065) 67.80  (71.134)
sTST: Change at last 7 nights: With DHR Number Analyzed 190 participants 245 participants 244 participants
38.98  (66.174) 62.41  (68.555) 79.95  (81.211)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sSOL, First 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.815
Confidence Interval (2-Sided) 95%
0.745 to 0.891
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sSOL, First 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.753
Confidence Interval (2-Sided) 95%
0.689 to 0.823
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sSOL, Last 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.671 to 0.837
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sSOL, Last 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSOL as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.689
Confidence Interval (2-Sided) 95%
0.618 to 0.769
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sWASO, First 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0093
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -12.41
Confidence Interval (2-Sided) 95%
-21.76 to -3.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.764
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sWASO, First 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -26.34
Confidence Interval (2-Sided) 95%
-35.68 to -16.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.762
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sWASO, Last 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0396
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -11.49
Confidence Interval (2-Sided) 95%
-22.42 to -0.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.573
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sWASO, Last 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0002
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sWASO as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -20.57
Confidence Interval (2-Sided) 95%
-31.51 to -9.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.574
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sTST, First 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0007
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baselines sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 19.05
Confidence Interval (2-Sided) 95%
8.03 to 30.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.619
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sTST, First 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baselines sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 34.51
Confidence Interval (2-Sided) 95%
23.5 to 45.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.609
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sTST, Last 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0003
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 23.57
Confidence Interval (2-Sided) 95%
10.68 to 36.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.565
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sTST, Last 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sTST as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 37.82
Confidence Interval (2-Sided) 95%
24.94 to 50.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.565
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
Hide Description sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.
Time Frame First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 201 253 258
Mean (Standard Deviation)
Unit of Measure: % of subjective time in bed asleep
sSE: Baseline: With DHR Number Analyzed 201 participants 253 participants 258 participants
56.08  (17.343) 56.05  (17.094) 54.31  (18.318)
sSE: Change at 1st 7 nights: With DHR Number Analyzed 197 participants 251 participants 254 participants
6.73  (10.930) 10.56  (12.296) 13.97  (14.188)
sSE: Change at last 7 nights: With DHR Number Analyzed 190 participants 245 participants 244 participants
8.35  (13.273) 12.92  (13.884) 16.12  (16.300)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sSE, First 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0008
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 3.76
Confidence Interval (2-Sided) 95%
1.56 to 5.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.122
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sSE, First 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (First 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 6.84
Confidence Interval (2-Sided) 95%
4.64 to 9.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sSE, Last 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0005
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 4.61
Confidence Interval (2-Sided) 95%
2.02 to 7.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.319
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sSE, Last 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on MMRM model with factors of age group, region, treatment, visit (Last 7 Nights), and treatment-by-visit interaction as fixed effects, and the baseline sSE as a covariate.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.18
Confidence Interval (2-Sided) 95%
4.6 to 9.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.319
Estimation Comments [Not Specified]
14.Other Pre-specified Outcome
Title Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
Hide Description Objective sleep onset response: LPS less than or equal to (<=) 20 minutes (mins) provided baseline LPS was greater than (>) 30 mins. Subjective sleep onset response: sSOL <=20 mins provided mean baseline sSOL was >30 mins. Objective sleep maintenance response: WASO <=60 minutes provided baseline WASO was >60 mins and was reduced by >10 mins compared to baseline. Subjective sleep maintenance response: sWASO <=60 mins provided mean WASO was >60 mins and was reduced by >10 mins compared to baseline. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. Average data for Days 1 and 2, Days 29 and 30, and first and last 7 nights of treatment period was reported.
Time Frame Days 1/2, Days 29/30, first 7 night (approximately Week 1), and Last seven nights (approximately Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received zolpidem tartrate extended release (ZOL ER) 6.25 milligram (mg) and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 263 266 269
Measure Type: Number
Unit of Measure: percentage of participants
LPS: Days 1/2 15.4 10.3 15.8 17.8
LPS: Days 29/30 15.9 11.4 20.3 22.3
sSOL: First 7 nights (with DHR) 2.9 7.6 9.8 10.4
sSOL: Last 7 nights (with DHR) 7.2 8.7 16.9 14.5
WASO: Days 1/2 16.8 46.0 51.1 64.3
WASO: Days 29/30 22.1 34.6 44.4 46.1
sWASO: First 7 nights (with DHR) 9.6 16.7 16.9 20.4
sWASO: Last 7 nights (with DHR) 15.4 23.2 23.3 23.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments LPS, Days 1/2: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9028
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
-6.22 to 7.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments LPS, Days 1/2: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.4699
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 2.49
Confidence Interval (2-Sided) 95%
-4.2 to 9.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments LPS, Days 1/2: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0566
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 5.58
Confidence Interval (2-Sided) 95%
-0.14 to 11.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments LPS, Days 1/2: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0122
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.57
Confidence Interval (2-Sided) 95%
1.71 to 13.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments LPS, Days 29/30: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2176
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 4.42
Confidence Interval (2-Sided) 95%
-2.5 to 11.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments LPS, Days 29/30: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0773
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 6.47
Confidence Interval (2-Sided) 95%
-0.55 to 13.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments LPS, Days 29/30: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0054
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 8.85
Confidence Interval (2-Sided) 95%
2.68 to 15.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments LPS, Days 29/30: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0008
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 10.89
Confidence Interval (2-Sided) 95%
4.61 to 17.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sSOL, First 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.003
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
2.66 to 11.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sSOL, First 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0016
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
3.19 to 11.81
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sSOL, First 7 nights: Zolpidem, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3643
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 2.22
Confidence Interval (2-Sided) 95%
-2.56 to 7.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sSOL, First 7 nights: Zolpidem, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2553
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 2.82
Confidence Interval (2-Sided) 95%
-2.02 to 7.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sSOL, Last 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0016
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 9.69
Confidence Interval (2-Sided) 95%
3.98 to 15.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sSOL, Last 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0128
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.29
Confidence Interval (2-Sided) 95%
1.8 to 12.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sSOL, Last 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0051
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 8.16
Confidence Interval (2-Sided) 95%
2.51 to 13.81
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sSOL, Last 7nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0389
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 5.76
Confidence Interval (2-Sided) 95%
0.34 to 11.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments WASO, Days 1/2: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 34.26
Confidence Interval (2-Sided) 95%
26.46 to 42.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments WASO, Days 1/2: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 47.57
Confidence Interval (2-Sided) 95%
40.02 to 55.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments WASO, Days 1/2: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2534
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 4.89
Confidence Interval (2-Sided) 95%
-3.49 to 13.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments WASO: Days 1/2: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 18.25
Confidence Interval (2-Sided) 95%
10.1 to 26.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments WASO, Days 29/30: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 22.2
Confidence Interval (2-Sided) 95%
14.06 to 30.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments WASO, Days 29/30: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 24.13
Confidence Interval (2-Sided) 95%
16.16 to 32.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments WASO, Days 29/30: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.023
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 9.59
Confidence Interval (2-Sided) 95%
1.36 to 17.81
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments WASO, Days 29/30: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0058
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 11.43
Confidence Interval (2-Sided) 95%
3.38 to 19.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sWASO, First 7 nights: Placebo, Lemborexant 5
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0222
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
1.27 to 13.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sWASO, First 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0013
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 10.84
Confidence Interval (2-Sided) 95%
4.57 to 17.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sWASO, First 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9495
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-6.17 to 6.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sWASO: First 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2708
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 3.72
Confidence Interval (2-Sided) 95%
-2.88 to 10.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 5 mg
Comments sWASO, Last 7 nights: Placebo, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0322
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.91
Confidence Interval (2-Sided) 95%
0.86 to 14.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Placebo, Lemborexant 10 mg
Comments sWASO, Last 7 nights: Placebo, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0363
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 7.69
Confidence Interval (2-Sided) 95%
0.68 to 14.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 5 mg
Comments sWASO, Last 7 nights: Zolpidem ER, Lemborexant 5 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9885
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-7.14 to 7.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Zolpidem Tartrate Extended Release 6.25 mg, Lemborexant 10 mg
Comments sWASO, Last 7 nights: Zolpidem ER, Lemborexant 10 mg
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9651
Comments Based on Cochran-Mantel-Haenszel test stratified by age group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-7.31 to 6.99
Estimation Comments [Not Specified]
15.Other Pre-specified Outcome
Title Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31
Hide Description The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: severity of sleep onset; sleep maintenance; early morning awakening problems; sleep dissatisfaction; interference of sleep difficulties with daytime functioning; noticeability of the sleep problems by others; and distress caused by the sleep difficulties. A 5-point Likert scale was used to rate each item (from 0 = no problem to 4 = very severe problem) yielding a total score from 0 to 28.
Time Frame Baseline and Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose primary efficacy measurement at given time points.
Arm/Group Title Placebo Zolpidem Tartrate Extended Release 6.25 mg Lemborexant 5 mg Lemborexant 10 mg
Hide Arm/Group Description:
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received zolpidem tartrate extended release (ZOL ER) 6.25 milligram (mg) and lemborexant-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment period.
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
Overall Number of Participants Analyzed 208 263 266 269
Mean (Standard Deviation)
Unit of Measure: score on scale
Baseline Number Analyzed 208 participants 263 participants 266 participants 269 participants
11.21  (2.436) 11.06  (2.508) 10.91  (2.419) 10.84  (2.334)
Change at Day 31 Number Analyzed 198 participants 244 participants 257 participants 253 participants
-3.88  (3.559) -5.24  (3.764) -4.83  (3.593) -4.77  (3.735)