Trial Outcomes & Findings for Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) (NCT NCT02783729)
NCT ID: NCT02783729
Last Updated: 2024-11-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1006 participants
Primary outcome timeframe
Baseline, Days 29/30
Results posted on
2024-11-12
Participant Flow
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.
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.
Participant milestones
| Measure |
Placebo
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Zolpidem Tartrate Extended Release 6.25 mg
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.
|
Lemborexant 5 mg
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
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 Study
STARTED
|
208
|
263
|
266
|
269
|
|
Overall Study
COMPLETED
|
198
|
246
|
258
|
260
|
|
Overall Study
NOT COMPLETED
|
10
|
17
|
8
|
9
|
Reasons for withdrawal
| Measure |
Placebo
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Zolpidem Tartrate Extended Release 6.25 mg
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.
|
Lemborexant 5 mg
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
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 Study
Lack of Efficacy
|
1
|
0
|
0
|
0
|
|
Overall Study
Adverse Event
|
2
|
6
|
2
|
3
|
|
Overall Study
Other
|
1
|
6
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
1
|
2
|
|
Overall Study
Participant's choice
|
2
|
1
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
1
|
0
|
Baseline Characteristics
Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1)
Baseline characteristics by cohort
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Zolpidem Tartrate Extended Release 6.25 mg
n=263 Participants
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.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
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
n=1006 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
63.4 years
STANDARD_DEVIATION 6.36 • n=5 Participants
|
64.3 years
STANDARD_DEVIATION 7.12 • n=7 Participants
|
63.7 years
STANDARD_DEVIATION 6.78 • n=5 Participants
|
64.2 years
STANDARD_DEVIATION 6.88 • n=4 Participants
|
63.9 years
STANDARD_DEVIATION 6.81 • n=21 Participants
|
|
Sex: Female, Male
Female
|
184 Participants
n=5 Participants
|
226 Participants
n=7 Participants
|
229 Participants
n=5 Participants
|
230 Participants
n=4 Participants
|
869 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
137 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
35 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
47 Participants
n=4 Participants
|
165 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
173 Participants
n=5 Participants
|
231 Participants
n=7 Participants
|
215 Participants
n=5 Participants
|
222 Participants
n=4 Participants
|
841 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
153 Participants
n=5 Participants
|
173 Participants
n=7 Participants
|
199 Participants
n=5 Participants
|
202 Participants
n=4 Participants
|
727 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
51 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
62 Participants
n=4 Participants
|
256 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Chinese
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other Asian
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Days 29/30Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
Baseline
|
43.89 minutes
Standard Deviation 33.596
|
44.86 minutes
Standard Deviation 36.528
|
44.61 minutes
Standard Deviation 32.986
|
—
|
|
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
Change at Days 29/30
|
-7.93 minutes
Standard Deviation 31.946
|
-19.53 minutes
Standard Deviation 33.054
|
-21.46 minutes
Standard Deviation 32.436
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 29/30Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
Baseline
|
68.89 Percentage of time in bed asleep
Standard Deviation 9.639
|
68.36 Percentage of time in bed asleep
Standard Deviation 11.268
|
67.85 Percentage of time in bed asleep
Standard Deviation 10.849
|
—
|
|
Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
Change at Days 29/30
|
5.35 Percentage of time in bed asleep
Standard Deviation 9.897
|
12.93 Percentage of time in bed asleep
Standard Deviation 9.741
|
14.09 Percentage of time in bed asleep
Standard Deviation 10.514
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 29/30Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
Baseline
|
111.75 minutes
Standard Deviation 37.179
|
113.44 minutes
Standard Deviation 38.953
|
114.83 minutes
Standard Deviation 39.997
|
—
|
|
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
Change at Days 29/30
|
-18.58 minutes
Standard Deviation 41.931
|
-43.89 minutes
Standard Deviation 39.264
|
-46.43 minutes
Standard Deviation 39.595
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 29/30Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=262 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
Baseline
|
78.04 minutes
Standard Deviation 33.849
|
76.60 minutes
Standard Deviation 32.903
|
76.88 minutes
Standard Deviation 32.126
|
—
|
|
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
Change at Days 29/30
|
-21.42 minutes
Standard Deviation 36.257
|
-27.19 minutes
Standard Deviation 33.047
|
-28.84 minutes
Standard Deviation 33.138
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 2/3Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=239 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=245 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=243 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
Baseline
|
26.96 one-third degree of angle of arc
Standard Deviation 26.502
|
26.40 one-third degree of angle of arc
Standard Deviation 20.781
|
36.29 one-third degree of angle of arc
Standard Deviation 197.282
|
—
|
|
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
Change at Days 2/3
|
8.47 one-third degree of angle of arc
Standard Deviation 69.894
|
-0.82 one-third degree of angle of arc
Standard Deviation 20.383
|
-8.97 one-third degree of angle of arc
Standard Deviation 146.679
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 1/2, and Days 29/30Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=262 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
LPS: Baseline
|
44.52 minutes
Standard Deviation 38.349
|
44.86 minutes
Standard Deviation 36.528
|
44.61 minutes
Standard Deviation 32.986
|
—
|
|
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
LPS: Change at Days 1/2
|
-12.56 minutes
Standard Deviation 32.506
|
-16.59 minutes
Standard Deviation 28.742
|
-19.48 minutes
Standard Deviation 31.809
|
—
|
|
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
LPS: Change at Days 29/30
|
-7.51 minutes
Standard Deviation 35.065
|
-19.53 minutes
Standard Deviation 33.054
|
-21.46 minutes
Standard Deviation 32.436
|
—
|
|
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
WASO: Baseline
|
114.31 minutes
Standard Deviation 39.992
|
113.44 minutes
Standard Deviation 38.953
|
114.83 minutes
Standard Deviation 39.997
|
—
|
|
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
WASO: Change at Days 1/2
|
-44.36 minutes
Standard Deviation 38.074
|
-49.96 minutes
Standard Deviation 39.578
|
-59.59 minutes
Standard Deviation 37.749
|
—
|
|
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
WASO: Change at Days 29/30
|
-36.50 minutes
Standard Deviation 43.406
|
-43.89 minutes
Standard Deviation 39.264
|
-46.43 minutes
Standard Deviation 39.595
|
—
|
|
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
TST: Baseline
|
326.99 minutes
Standard Deviation 54.852
|
328.00 minutes
Standard Deviation 54.224
|
325.07 minutes
Standard Deviation 52.819
|
—
|
|
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
TST: Change at Days 1/2
|
55.31 minutes
Standard Deviation 48.138
|
65.22 minutes
Standard Deviation 46.695
|
79.58 minutes
Standard Deviation 47.350
|
—
|
|
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
TST: Change at Days 29/30
|
43.34 minutes
Standard Deviation 54.012
|
61.99 minutes
Standard Deviation 46.817
|
67.86 minutes
Standard Deviation 52.117
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=259 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=264 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
sSOL: Baseline: With DHR
|
60.54 minutes
Standard Deviation 36.350
|
65.79 minutes
Standard Deviation 43.530
|
60.88 minutes
Standard Deviation 42.514
|
—
|
|
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
sSOL: 1st 7 nights: With DHR
|
-16.23 minutes
Standard Deviation 29.531
|
-22.54 minutes
Standard Deviation 32.812
|
-21.88 minutes
Standard Deviation 29.269
|
—
|
|
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
sSOL: last 7 nights: With DHR
|
-17.04 minutes
Standard Deviation 30.683
|
-25.20 minutes
Standard Deviation 34.854
|
-24.79 minutes
Standard Deviation 34.068
|
—
|
|
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
sWASO: Baseline: With DHR
|
173.06 minutes
Standard Deviation 77.212
|
166.76 minutes
Standard Deviation 82.047
|
175.35 minutes
Standard Deviation 83.453
|
—
|
|
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
sWASO: Change at 1st 7 nights: With DHR
|
-48.91 minutes
Standard Deviation 51.761
|
-39.33 minutes
Standard Deviation 55.022
|
-55.06 minutes
Standard Deviation 66.696
|
—
|
|
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
sWASO: Change at last 7 nights: With DHR
|
-63.52 minutes
Standard Deviation 64.161
|
-44.51 minutes
Standard Deviation 58.090
|
-57.96 minutes
Standard Deviation 72.791
|
—
|
|
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
sTST: Baseline: With DHR
|
273.07 minutes
Standard Deviation 81.207
|
275.74 minutes
Standard Deviation 83.650
|
266.10 minutes
Standard Deviation 92.164
|
—
|
|
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
sTST: Change at 1st 7 nights: With DHR
|
56.99 minutes
Standard Deviation 62.880
|
50.30 minutes
Standard Deviation 60.065
|
67.80 minutes
Standard Deviation 71.134
|
—
|
|
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
sTST: Change at last 7 nights: With DHR
|
71.01 minutes
Standard Deviation 76.574
|
62.41 minutes
Standard Deviation 68.555
|
79.95 minutes
Standard Deviation 81.211
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=247 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=253 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=258 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
sSE: Baseline: With DHR
|
55.49 % of subjective time in bed asleep
Standard Deviation 15.802
|
56.05 % of subjective time in bed asleep
Standard Deviation 17.094
|
54.31 % of subjective time in bed asleep
Standard Deviation 18.318
|
—
|
|
Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
sSE: Change at 1st 7 nights: With DHR
|
11.96 % of subjective time in bed asleep
Standard Deviation 12.526
|
10.56 % of subjective time in bed asleep
Standard Deviation 12.296
|
13.97 % of subjective time in bed asleep
Standard Deviation 14.188
|
—
|
|
Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
sSE: Change at last 7 nights: With DHR
|
14.83 % of subjective time in bed asleep
Standard Deviation 15.011
|
12.92 % of subjective time in bed asleep
Standard Deviation 13.884
|
16.12 % of subjective time in bed asleep
Standard Deviation 16.300
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 1/2Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
LPS: Baseline
|
43.89 minutes
Standard Deviation 33.596
|
44.86 minutes
Standard Deviation 36.528
|
44.61 minutes
Standard Deviation 32.986
|
—
|
|
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
LPS: Change at Days 1/2
|
-6.45 minutes
Standard Deviation 32.618
|
-16.59 minutes
Standard Deviation 28.742
|
-19.48 minutes
Standard Deviation 31.809
|
—
|
|
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
WASO: Baseline
|
111.75 minutes
Standard Deviation 37.179
|
113.44 minutes
Standard Deviation 38.953
|
114.83 minutes
Standard Deviation 39.997
|
—
|
|
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
WASO: Change at Days 1/2
|
-15.07 minutes
Standard Deviation 36.938
|
-49.96 minutes
Standard Deviation 39.578
|
-59.59 minutes
Standard Deviation 37.749
|
—
|
|
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
WASO2H: Baseline
|
74.44 minutes
Standard Deviation 30.109
|
76.60 minutes
Standard Deviation 32.903
|
76.88 minutes
Standard Deviation 32.126
|
—
|
|
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
WASO2H: Change at Days 1/2
|
-7.06 minutes
Standard Deviation 31.097
|
-30.28 minutes
Standard Deviation 32.056
|
-37.10 minutes
Standard Deviation 30.815
|
—
|
|
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
TST: Baseline
|
330.67 minutes
Standard Deviation 46.268
|
328.00 minutes
Standard Deviation 54.224
|
325.07 minutes
Standard Deviation 52.819
|
—
|
|
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
TST: Change at Days 1/2
|
19.44 minutes
Standard Deviation 43.348
|
65.22 minutes
Standard Deviation 46.695
|
79.58 minutes
Standard Deviation 47.350
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 1/2Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
SE: Baseline
|
68.89 Percentage of time in bed asleep
Standard Deviation 9.639
|
68.36 Percentage of time in bed asleep
Standard Deviation 11.268
|
67.85 Percentage of time in bed asleep
Standard Deviation 10.849
|
—
|
|
Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
SE: Change at Days 1/2
|
4.22 Percentage of time in bed asleep
Standard Deviation 9.033
|
13.60 Percentage of time in bed asleep
Standard Deviation 9.725
|
16.48 Percentage of time in bed asleep
Standard Deviation 9.623
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 29/30Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=266 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
TST: Baseline
|
330.67 minutes
Standard Deviation 46.268
|
328.00 minutes
Standard Deviation 54.224
|
325.07 minutes
Standard Deviation 52.819
|
—
|
|
Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
WASO2H: Baseline
|
74.44 minutes
Standard Deviation 30.109
|
76.60 minutes
Standard Deviation 32.903
|
76.88 minutes
Standard Deviation 32.126
|
—
|
|
Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
WASO2H: Days 29 /30
|
-8.92 minutes
Standard Deviation 31.909
|
-27.19 minutes
Standard Deviation 33.047
|
-28.84 minutes
Standard Deviation 33.138
|
—
|
|
Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
TST: Days 29/30
|
25.65 minutes
Standard Deviation 47.587
|
61.99 minutes
Standard Deviation 46.817
|
67.86 minutes
Standard Deviation 52.117
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=206 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=264 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSOL: Baseline: With DHR
|
55.90 minutes
Standard Deviation 37.389
|
65.79 minutes
Standard Deviation 43.530
|
60.88 minutes
Standard Deviation 42.514
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSOL: Change at 1st 7 nights :With DHR
|
-6.83 minutes
Standard Deviation 23.040
|
-22.54 minutes
Standard Deviation 32.812
|
-21.88 minutes
Standard Deviation 29.269
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSOL: Change at last 7 nights: With DHR
|
-8.10 minutes
Standard Deviation 27.447
|
-25.20 minutes
Standard Deviation 34.854
|
-24.79 minutes
Standard Deviation 34.068
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sWASO: Baseline: With DHR
|
170.89 minutes
Standard Deviation 80.676
|
166.76 minutes
Standard Deviation 82.047
|
175.35 minutes
Standard Deviation 83.453
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sWASO: Change at 1st 7 nights: With DHR
|
-27.92 minutes
Standard Deviation 45.201
|
-39.33 minutes
Standard Deviation 55.022
|
-55.06 minutes
Standard Deviation 66.696
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sWASO: Change at last 7 nights: With DHR
|
-36.01 minutes
Standard Deviation 57.584
|
-44.51 minutes
Standard Deviation 58.090
|
-57.96 minutes
Standard Deviation 72.791
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sTST: Baseline: With DHR
|
276.23 minutes
Standard Deviation 87.649
|
275.74 minutes
Standard Deviation 83.650
|
266.10 minutes
Standard Deviation 92.164
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sTST: Change at 1st 7 nights: With DHR
|
30.86 minutes
Standard Deviation 57.437
|
50.30 minutes
Standard Deviation 60.065
|
67.80 minutes
Standard Deviation 71.134
|
—
|
|
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sTST: Change at last 7 nights: With DHR
|
38.98 minutes
Standard Deviation 66.174
|
62.41 minutes
Standard Deviation 68.555
|
79.95 minutes
Standard Deviation 81.211
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=201 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=253 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=258 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSE: Change at last 7 nights: With DHR
|
8.35 % of subjective time in bed asleep
Standard Deviation 13.273
|
12.92 % of subjective time in bed asleep
Standard Deviation 13.884
|
16.12 % of subjective time in bed asleep
Standard Deviation 16.300
|
—
|
|
Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSE: Baseline: With DHR
|
56.08 % of subjective time in bed asleep
Standard Deviation 17.343
|
56.05 % of subjective time in bed asleep
Standard Deviation 17.094
|
54.31 % of subjective time in bed asleep
Standard Deviation 18.318
|
—
|
|
Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
sSE: Change at 1st 7 nights: With DHR
|
6.73 % of subjective time in bed asleep
Standard Deviation 10.930
|
10.56 % of subjective time in bed asleep
Standard Deviation 12.296
|
13.97 % of subjective time in bed asleep
Standard Deviation 14.188
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 1/2, Days 29/30, first 7 night (approximately Week 1), and Last seven nights (approximately Week 4)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=263 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=266 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
LPS: Days 1/2
|
15.4 percentage of participants
|
10.3 percentage of participants
|
15.8 percentage of participants
|
17.8 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
LPS: Days 29/30
|
15.9 percentage of participants
|
11.4 percentage of participants
|
20.3 percentage of participants
|
22.3 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
sSOL: First 7 nights (with DHR)
|
2.9 percentage of participants
|
7.6 percentage of participants
|
9.8 percentage of participants
|
10.4 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
sSOL: Last 7 nights (with DHR)
|
7.2 percentage of participants
|
8.7 percentage of participants
|
16.9 percentage of participants
|
14.5 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
WASO: Days 1/2
|
16.8 percentage of participants
|
46.0 percentage of participants
|
51.1 percentage of participants
|
64.3 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
WASO: Days 29/30
|
22.1 percentage of participants
|
34.6 percentage of participants
|
44.4 percentage of participants
|
46.1 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
sWASO: First 7 nights (with DHR)
|
9.6 percentage of participants
|
16.7 percentage of participants
|
16.9 percentage of participants
|
20.4 percentage of participants
|
|
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
sWASO: Last 7 nights (with DHR)
|
15.4 percentage of participants
|
23.2 percentage of participants
|
23.3 percentage of participants
|
23.0 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Day 31Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=263 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=266 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
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
Baseline
|
11.21 score on scale
Standard Deviation 2.436
|
11.06 score on scale
Standard Deviation 2.508
|
10.91 score on scale
Standard Deviation 2.419
|
10.84 score on scale
Standard Deviation 2.334
|
|
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
Change at Day 31
|
-3.88 score on scale
Standard Deviation 3.559
|
-5.24 score on scale
Standard Deviation 3.764
|
-4.83 score on scale
Standard Deviation 3.593
|
-4.77 score on scale
Standard Deviation 3.735
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Day 31Population: 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.
The FSS is a self-report scale on which participants are instructed to choose a number from 1 to 7 that indicates their degree of agreement with each of 9 statements about their fatigue where "1" indicates strongly disagree, and "7" indicates strongly agree. The FSS total score was the sum of all responses to the 9 questions. The FSS average item score was the average of the score for each item. Higher total scores and higher average item scores indicated greater fatigue.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=263 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=266 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31
Baseline
|
37.48 score on scale
Standard Deviation 13.602
|
37.15 score on scale
Standard Deviation 13.788
|
37.47 score on scale
Standard Deviation 13.518
|
37.42 score on scale
Standard Deviation 13.111
|
|
Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31
Change at Day 31
|
-6.75 score on scale
Standard Deviation 11.916
|
-7.80 score on scale
Standard Deviation 12.879
|
-8.14 score on scale
Standard Deviation 13.411
|
-8.00 score on scale
Standard Deviation 14.058
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 2/3Population: 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.
POA reflects the ability to focus attention and process information. POA is calculated from the sum of simple reaction time, choice reaction time and digit vigilance. SOMT reflects time taken to retrieve information from working and episodic memory. SOMT is a composite score created by combining numerical working memory and spatial working memory and word recognition and picture recognition. Cognitive performance assessment was done by a computerized performance assessment battery (PAB) which was administered on a laptop computer. A positive change from baseline reflects impairment and a lower value of decrease from baseline indicates better performance. Change from baseline to average POA and SOMT on Days 2 and 3 was reported.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=263 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=266 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=269 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3
POA : Days 2/3
|
-14.2 millisecond
Standard Deviation 149.31
|
37.1 millisecond
Standard Deviation 107.15
|
8.9 millisecond
Standard Deviation 154.33
|
31.1 millisecond
Standard Deviation 142.38
|
|
Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3
POA: Baseine
|
1421.0 millisecond
Standard Deviation 210.27
|
1418.7 millisecond
Standard Deviation 195.95
|
1452.9 millisecond
Standard Deviation 263.04
|
1399.2 millisecond
Standard Deviation 192.47
|
|
Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3
SOMT: Baseline
|
4507.7 millisecond
Standard Deviation 1098.73
|
4513.8 millisecond
Standard Deviation 1097.65
|
4674.3 millisecond
Standard Deviation 1174.74
|
4619.8 millisecond
Standard Deviation 1065.00
|
|
Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3
SOMT: Days 2/3
|
-177.9 millisecond
Standard Deviation 668.77
|
60.7 millisecond
Standard Deviation 749.12
|
-185.1 millisecond
Standard Deviation 645.18
|
-152.8 millisecond
Standard Deviation 722.49
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Days 2/3Population: FAS was group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement at given time points.
QOM represents the ability to store information in memory and subsequently retrieve it. It is a composite score created by combining accuracy measures from 2 sets of working memory and 4 sets of episodic memory. Two sets of working memory were included: numerical and spatial working memory, and ranges from -2 to 2. Four sets of episodic memory were included: immediate and delayed word recall, and word and picture recognition, and ranges from -200 to 400. COA is the ability to sustain attention. Number of correct responses (out of 50) for choice reaction time was added to total number of targets correctly identified (out of 45) digit vigilance minus number of false alarms (total score of -45 to 95). Higher values were better. Change from baseline to average QOM and COA on Days 2 and 3 was reported.
Outcome measures
| Measure |
Placebo
n=195 Participants
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 5 mg
n=239 Participants
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=249 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=246 Participants
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3
QOM: Baseline
|
342.2 units on scale
Standard Deviation 66.03
|
350.0 units on scale
Standard Deviation 65.30
|
345.7 units on scale
Standard Deviation 67.60
|
340.7 units on scale
Standard Deviation 72.75
|
|
Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3
QOM: Change at Days 2/3
|
3.5 units on scale
Standard Deviation 45.20
|
-12.1 units on scale
Standard Deviation 46.94
|
1.4 units on scale
Standard Deviation 44.21
|
-2.8 units on scale
Standard Deviation 44.11
|
|
Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3
COA: Baseline
|
90.7 units on scale
Standard Deviation 4.77
|
90.6 units on scale
Standard Deviation 6.0
|
91.0 units on scale
Standard Deviation 5.15
|
91.3 units on scale
Standard Deviation 4.15
|
|
Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3
COA: Change at Days2/3
|
0.0 units on scale
Standard Deviation 4.16
|
-1.0 units on scale
Standard Deviation 4.48
|
0.2 units on scale
Standard Deviation 4.95
|
-0.7 units on scale
Standard Deviation 3.92
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Zolpidem Tartrate Extended Release 6.25 mg
Serious events: 4 serious events
Other events: 18 other events
Deaths: 0 deaths
Lemborexant 5 mg
Serious events: 2 serious events
Other events: 27 other events
Deaths: 0 deaths
Lemborexant 10 mg
Serious events: 0 serious events
Other events: 28 other events
Deaths: 0 deaths
Run -in Period Placebo
Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=209 participants at risk
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Zolpidem Tartrate Extended Release 6.25 mg
n=263 participants at risk
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.
|
Lemborexant 5 mg
n=266 participants at risk
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=268 participants at risk
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Run -in Period Placebo
n=1006 participants at risk
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once on each night for 7 consecutive nights up to Baseline (Day 1), immediately before the time the participant intended to try to sleep of run-in period.
|
|---|---|---|---|---|---|
|
Vascular disorders
Peripheral vascular disorder
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/263 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/266 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/263 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/266 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
General disorders
Chest pain
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/263 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/266 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/263 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/266 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/263 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/266 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/263 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/266 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/263 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/266 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/209 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/263 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.38%
1/266 • Number of events 1 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/268 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
Other adverse events
| Measure |
Placebo
n=209 participants at risk
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Zolpidem Tartrate Extended Release 6.25 mg
n=263 participants at risk
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.
|
Lemborexant 5 mg
n=266 participants at risk
Participants received lemborexant 5 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Lemborexant 10 mg
n=268 participants at risk
Participants received lemborexant 10 mg and zolpidem-matched placebo, tablets, orally, once daily from Day 1 up to Day 30 in the Treatment Period.
|
Run -in Period Placebo
n=1006 participants at risk
Participants received lemborexant-matched placebo and zolpidem matched placebo, tablets, orally, once on each night for 7 consecutive nights up to Baseline (Day 1), immediately before the time the participant intended to try to sleep of run-in period.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
6.2%
13/209 • Number of events 13 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
5.3%
14/263 • Number of events 21 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
6.4%
17/266 • Number of events 21 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
4.9%
13/268 • Number of events 15 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
3.4%
34/1006 • Number of events 34 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
|
Nervous system disorders
Somnolence
|
1.9%
4/209 • Number of events 4 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
1.5%
4/263 • Number of events 5 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
4.1%
11/266 • Number of events 11 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
7.1%
19/268 • Number of events 20 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
0.00%
0/1006 • Run-in Phase (Day -7) up to End of treatment (Day 44)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place