Chronic Insomnia, Adults, Elderly
Conditions
Keywords
Chronic Insomnia, Adults, Elderly
Brief summary
This is a multicenter, multiple dose, randomized, double-blind, placebo-controlled, parallel-group, Bayesian adaptive, dose response study in subjects with chronic insomnia. Subjects will be randomized to 1 of 6 doses of E2006 (1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg) or placebo.
Detailed description
The study will have 2 phases, Prerandomization and Randomization. The Prerandomization Phase will last up to 21 days and will consist of a Screening Period (Days -21 to -2) and a Baseline Period (Day -1). Following the Baseline Period, all eligible subjects will be randomized, in a double-blind manner, to receive E2006 or placebo for 15 nights during the Treatment Period (Days 1 to 15), then all subjects will receive placebo, in a single-blind manner, for 2 nights (Days 16 to 17) during the Rebound Insomnia Assessment Period (Days 16 to 18). Subjects will not receive any treatment during the Follow-up Period (Days 19 to 29). All subjects will come to the clinic for screening procedures. During the Screening Period, subjects will complete the Sleep Diary each day. Polysomnographic sleep will be measured during the Screening Period on 2 consecutive nights between Day -9 and Day -3. These 8-hour polysomnograms (PSGs) will start at the median habitual bedtime calculated from responses on the Sleep Diary completed 7 days immediately prior to the first PSG night. Subjects may leave the clinic between the screening/baseline PSG nights.
Interventions
DRUGE2006
E2006 1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg, in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights
DRUGPlacebo
E2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following criteria to be included in this study: 1. Male or female subjects age 18 to 80 years at the time of informed consent 2. Meets the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Insomnia Disorder 3. Subjective Sleep Onset Latency (sSOL) typically greater than or equal to 30 minutes in the last 4 weeks and/or subjective WASO (sWASO) typically greater than or equal to 60 minutes in the last 4 weeks 4. Regular time in bed between 6.5 and 9.0 hours 5. Regular bedtime between 21:00 and 24:00 and regular waketime between 05:00 and 09:00 6. Insomnia Severity Index (ISI) score greater than or equal to 15 at Screening 7. Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary completed for 7 nights prior to the first screening/baseline PSG 8. Objective (PSG) evidence of insomnia at the screening/baseline PSGs as follows: 1. LPS average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 15 minutes and/or 2. WASO average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 20 minutes 3. SE average lesser than or equal to 85% on the 2 consecutive screening/baseline PSGs, with neither night greater than 87.5% 9. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use two highly effective method of contraception 10. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation. 11. Provide written informed consent 12. Willing to stay in bed for at least 8 hours each night spent in the clinic 13. Willing and able to comply with all aspects of the protocol
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from this study: 1. Females who are pregnant (positive beta-human chorionic gonadotropin \[B-hCG\] test) or breastfeeding 2. Any lifetime diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement (REM) behavior disorder, or narcolepsy 3. Aged 18 to 64 years: Apnea-Hypopnea Index greater than or equal to 10, or Periodic Limb Movements with Arousal Index greater than or equal to 10 on first (diagnostic) PSG night at Screening. Aged 65 to 80 years: Apnea-Hypopnea Index greater than 15, or Periodic Limb Movements with Arousal Index greater than 15 on first (diagnostic) PSG night at Screening 4. Beck Depression Inventory (BDI) - II score greater than 19 at Screening 5. Beck Anxiety Inventory (BAI) score greater than 15 at Screening 6. Used a prescription for any modality of treatment for insomnia, including cognitive behavioral therapy, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline 7. Used any medication or sleep aid with known effects on sleep, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline 8. Used any prohibited prescription or over-the-counter concomitant medications within the week prior to the first screening/baseline PSG. 9. Transmeridian travel across 3 or more time zones in the 2 weeks prior to Screening, or plans to travel across 3 or more time zones during study 10. Unwilling to limit caffeine consumption to lesser than or equal to 600 mg caffeine (approximately four 6-oz cups of caffeinated coffee, or three 12-oz caffeinated sodas, or three 8-oz caffeinated tea beverages), avoid caffeine after 18:00 throughout the study, and avoid caffeine after 13:00 on PSG visits 11. Unwilling to limit alcohol intake to two or fewer drinks per day throughout the study, or to refrain from any alcohol for 3 hours prior to bedtime while at home throughout the study, or any alcohol on days and nights spent in the clinic. A drink is defined as approximately 12 oz (360 mL) of beer, 4 oz (120 mL) of wine, or 1 oz (30 mL) of liquor. 12. Any subject that has a known history of malaria or has traveled to a country with known malarial risk (i.e., are designated as 'high' or 'moderate' risk country according to the list available at http://www.cdc.gov/malaria) within the last year. 13. A prolonged QT/QT interval corrected for heart rate (QTc) interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTc interval greater than 450 ms). A history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolong the QT/QTc interval. 14. Any suicidal ideation with intent with or without a plan at Screening, Baseline, or within 6 months before Screening (i.e., answering Yes to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale \[C-SSRS\]) 15. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS) 16. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments 17. Hypersensitivity to the study drug or any of the excipients 18. Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator(s) would compromise the subject's ability to safely complete the study 19. Scheduled for surgery during the study 20. Known to be human immunodeficiency virus (HIV) positive 21. Active viral hepatitis (B or C) as demonstrated by positive serology 22. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years 23. History of drug or alcohol dependency or abuse within approximately the last 2 years 24. Unwilling to refrain from use of illegal (or legalized) recreational drugs during the study or test positive for illegal (or legalized) drugs at Screening, Baseline, or Day 14 25. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5x the half-life, whichever is longer preceding informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | Baseline up to Day 3 | The utility of a dose was a function of both Sleep Efficiency (SE) and Karolinska Sleepiness Scale (KSS), constructed by specifying the 1-dimensional component for each outcome measure and then combining them multiplicatively. Sufficient utility was defined as a probability of having utility function \>1. Probability of having utility function \>1 at the end of study visit (full analysis) was reported. |
| Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | 1 hour after morning wake time at Baseline and Days 15-16 | The KSS was used to measure next-day residual effects at prespecified time points. The KSS was a 9-point scale on which the participant rated their sleepiness from 1 (extremely alert) to 9 (extremely sleepy/fighting sleep), where higher scores indicated an increase in sleepiness. The end of treatment score was calculated by the mean scores at the timepoint at 1 hour after morning wake time of Day 15 and 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Baseline, Days 1-2, and Days 14-15 | Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline. |
| Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Baseline, Days 1-2, and Days 14-15 | LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline. |
| Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Baseline, Days 1-2, and Days 14-15 | WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline. |
| Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | Baseline, Days 1-2, and Days 14-15 | Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean SE of Days 14-15 minus change from baseline of mean SE of Days 1-2. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. |
| Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | Baseline and Days 1-2, and Days 14-15 | Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean LPS of Days 14-15 minus change from baseline of mean LPS of Days 1-2. LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep. |
| Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | Baseline, Days 1-2, and Days 14-15 | Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean WASO of Days 14-15 minus change from baseline of mean WASO of Days 1-2. WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance. |
| Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | Baseline and Days 16-17 | Rebound insomnia was assessed by comparing the change from baseline of the mean SE on Days 16-17. Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. A negative change from baseline in SE indicated that SE was worse on Days 16 and 17 than at Baseline, which was considered as evidence for rebound insomnia. |
| Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days) | — |
| Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | Baseline up to Day 30 | — |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to Day 30 | — |
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | Baseline up to Day 30 | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 23 investigative sites in the United States from 13 Nov 2013 to 29 Apr 2014.
Pre-assignment details
A total of 616 participants were screened, of which 325 were screen failures and 291 were randomized to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Lemborexant 1 mg Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase. | 32 |
| Lemborexant 2.5 mg Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase. | 27 |
| Lemborexant 5 mg Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase. | 38 |
| Lemborexant 10 mg Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase. | 32 |
| Lemborexant 15 mg Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase. | 56 |
| Lemborexant 25 mg Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase. | 50 |
| Placebo Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase. | 56 |
| Total | 291 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other | 3 | 1 | 0 | 2 | 1 | 1 | 2 |
| Overall Study | Participant choice | 2 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Lemborexant 1 mg | Lemborexant 2.5 mg | Lemborexant 5 mg | Lemborexant 10 mg | Lemborexant 15 mg | Lemborexant 25 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.3 Years STANDARD_DEVIATION 13 | 49.7 Years STANDARD_DEVIATION 14.3 | 51.1 Years STANDARD_DEVIATION 14.3 | 47.1 Years STANDARD_DEVIATION 13.7 | 44.0 Years STANDARD_DEVIATION 14.6 | 48.9 Years STANDARD_DEVIATION 13.4 | 47.1 Years STANDARD_DEVIATION 15.6 | 48.3 Years STANDARD_DEVIATION 14.4 |
| Sex: Female, Male Female | 23 Participants | 17 Participants | 23 Participants | 20 Participants | 32 Participants | 31 Participants | 36 Participants | 182 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 15 Participants | 12 Participants | 24 Participants | 19 Participants | 20 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 27 | 0 / 38 | 0 / 32 | 0 / 56 | 0 / 50 | 0 / 56 |
| other Total, other adverse events | 11 / 32 | 11 / 27 | 16 / 38 | 19 / 32 | 31 / 56 | 30 / 50 | 21 / 56 |
| serious Total, serious adverse events | 0 / 32 | 0 / 27 | 0 / 38 | 0 / 32 | 0 / 56 | 1 / 50 | 1 / 56 |
Outcome results
Primary
Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment
The KSS was used to measure next-day residual effects at prespecified time points. The KSS was a 9-point scale on which the participant rated their sleepiness from 1 (extremely alert) to 9 (extremely sleepy/fighting sleep), where higher scores indicated an increase in sleepiness. The end of treatment score was calculated by the mean scores at the timepoint at 1 hour after morning wake time of Day 15 and 16.
Time frame: 1 hour after morning wake time at Baseline and Days 15-16
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, number of participants analyzed (N) represents participants who were available for analysis at the specified timepoints.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant 1 mg | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | 0.29 Units on a scale | Standard Error 0.219 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | -0.10 Units on a scale | Standard Error 0.234 |
| Lemborexant 5 mg | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | 0.20 Units on a scale | Standard Error 0.2 |
| Lemborexant 10 mg | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | -0.22 Units on a scale | Standard Error 0.219 |
| Lemborexant 15 mg | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | 0.16 Units on a scale | Standard Error 0.166 |
| Lemborexant 25 mg | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | 0.45 Units on a scale | Standard Error 0.18 |
| Placebo | Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment | -0.23 Units on a scale | Standard Error 0.17 |
p-value: 0.065195% CI: [-0.03, 1.06]ANCOVA
p-value: 0.64995% CI: [-0.44, 0.7]ANCOVA
p-value: 0.105995% CI: [-0.09, 0.94]ANCOVA
p-value: 0.9818ANCOVA
p-value: 0.107195% CI: [-0.08, 0.85]ANCOVA
p-value: 0.006395% CI: [0.19, 1.17]ANCOVA
Primary
Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis
The utility of a dose was a function of both Sleep Efficiency (SE) and Karolinska Sleepiness Scale (KSS), constructed by specifying the 1-dimensional component for each outcome measure and then combining them multiplicatively. Sufficient utility was defined as a probability of having utility function \>1. Probability of having utility function \>1 at the end of study visit (full analysis) was reported.
Time frame: Baseline up to Day 3
Population: The full analysis set (FAS) included all participants who were randomized, received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lemborexant 1 mg | Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | 0.8789 probability |
| Lemborexant 2.5 mg | Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | 0.8920 probability |
| Lemborexant 5 mg | Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | 0.9032 probability |
| Lemborexant 10 mg | Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | 0.9406 probability |
| Lemborexant 15 mg | Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | 0.9866 probability |
| Lemborexant 25 mg | Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis | 0.9675 probability |
Secondary
Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15
LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.
Time frame: Baseline, Days 1-2, and Days 14-15
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug, had at least 1 post-dose primary efficacy measurement with both baseline and post baseline data available for analysis at each timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant 1 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -42.92 minutes | Standard Deviation 41.855 |
| Lemborexant 1 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -41.23 minutes | Standard Deviation 34.618 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -52.74 minutes | Standard Deviation 50.149 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -54.24 minutes | Standard Deviation 44.918 |
| Lemborexant 5 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -47.72 minutes | Standard Deviation 39.389 |
| Lemborexant 5 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -51.86 minutes | Standard Deviation 41.994 |
| Lemborexant 10 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -46.80 minutes | Standard Deviation 46.106 |
| Lemborexant 10 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -56.14 minutes | Standard Deviation 45.553 |
| Lemborexant 15 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -51.59 minutes | Standard Deviation 36.728 |
| Lemborexant 15 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -51.95 minutes | Standard Deviation 41.926 |
| Lemborexant 25 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -50.16 minutes | Standard Deviation 43.14 |
| Lemborexant 25 mg | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -50.79 minutes | Standard Deviation 40.16 |
| Placebo | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -22.90 minutes | Standard Deviation 44.457 |
| Placebo | Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -22.43 minutes | Standard Deviation 29.045 |
Comparison: Days 1-2p-value: 0.140795% CI: [0.54, 1.09]ANCOVA
p-value: 0.001895% CI: [0.38, 0.8]ANCOVA
Comparison: Days 1-2p-value: 0.002595% CI: [0.43, 0.83]ANCOVA
Comparison: Days 1-2p-value: 0.000695% CI: [0.38, 0.76]ANCOVA
Comparison: Days 1-2p-value: <0.000195% CI: [0.38, 0.7]ANCOVA
Comparison: Days 1-2:p-value: <0.000195% CI: [0.29, 0.54]ANCOVA
Comparison: Days 14-15p-value: 0.115895% CI: [0.49, 1.08]ANCOVA
Comparison: Days 14-15p-value: 0.00195% CI: [0.33, 0.75]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [0.32, 0.69]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [0.21, 0.47]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [0.29, 0.57]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [0.24, 0.48]ANCOVA
Secondary
Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15
Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.
Time frame: Baseline, Days 1-2, and Days 14-15
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug, had at least 1 post-dose primary efficacy measurement with both baseline and post baseline data available for analysis at each timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant 1 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 18.72 percentage of sleep time | Standard Error 1.366 |
| Lemborexant 1 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 14.43 percentage of sleep time | Standard Error 1.428 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 18.59 percentage of sleep time | Standard Error 1.487 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 18.02 percentage of sleep time | Standard Error 1.528 |
| Lemborexant 5 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 19.89 percentage of sleep time | Standard Error 1.25 |
| Lemborexant 5 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 19.85 percentage of sleep time | Standard Error 1.302 |
| Lemborexant 10 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 22.25 percentage of sleep time | Standard Error 1.361 |
| Lemborexant 10 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 21.87 percentage of sleep time | Standard Error 1.421 |
| Lemborexant 15 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 24.22 percentage of sleep time | Standard Error 1.029 |
| Lemborexant 15 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 21.97 percentage of sleep time | Standard Error 1.077 |
| Lemborexant 25 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 24.28 percentage of sleep time | Standard Error 1.091 |
| Lemborexant 25 mg | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 22.96 percentage of sleep time | Standard Error 1.169 |
| Placebo | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | 14.16 percentage of sleep time | Standard Error 1.031 |
| Placebo | Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | 14.08 percentage of sleep time | Standard Error 1.1 |
Comparison: Days 1-2p-value: 0.008395% CI: [1.19, 7.94]ANCOVA
Comparison: Days 1-2p-value: 0.015195% CI: [0.86, 8.01]ANCOVA
Comparison: Days 1-2p-value: 0.000595% CI: [2.54, 8.93]ANCOVA
Comparison: Days 1-2p-value: <0.000195% CI: [4.73, 11.45]ANCOVA
Comparison: Days 1-2p-value: <0.000195% CI: [7.2, 12.93]ANCOVA
Comparison: Days 1-2p-value: <0.000195% CI: [7.18, 13.08]ANCOVA
Comparison: Days 14-15p-value: 0.850595% CI: [-3.22, 3.9]ANCOVA
Comparison: Days 14-15p-value: 0.03895% CI: [0.22, 7.66]ANCOVA
Comparison: Days 14-15p-value: 0.000895% CI: [2.4, 9.12]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [4.24, 11.32]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [4.86, 10.92]ANCOVA
Comparison: Days 14-15p-value: <0.000195% CI: [5.72, 12.02]ANCOVA
Secondary
Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15
WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.
Time frame: Baseline, Days 1-2, and Days 14-15
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, number of participants analyzed (N) represents participants who were available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant 1 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -52.11 minutes | Standard Error 5.441 |
| Lemborexant 1 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -32.46 minutes | Standard Error 6.159 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -43.33 minutes | Standard Error 5.915 |
| Lemborexant 2.5 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -40.47 minutes | Standard Error 6.581 |
| Lemborexant 5 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -52.29 minutes | Standard Error 5.423 |
| Lemborexant 5 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -48.84 minutes | Standard Error 5.609 |
| Lemborexant 10 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -60.84 minutes | Standard Error 1.302 |
| Lemborexant 10 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -52.88 minutes | Standard Error 6.129 |
| Lemborexant 15 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -70.38 minutes | Standard Error 4.103 |
| Lemborexant 15 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -58.95 minutes | Standard Error 4.651 |
| Lemborexant 25 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -66.87 minutes | Standard Error 4.342 |
| Lemborexant 25 mg | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -59.67 minutes | Standard Error 5.039 |
| Placebo | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 1-2 | -41.03 minutes | Standard Error 4.095 |
| Placebo | Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 | Days 14-15 | -38.15 minutes | Standard Error 4.728 |
Comparison: Days 1-2p-value: 0.10595% CI: [-24.48, 2.33]ANCOVA
Comparison: Days 1-2p-value: 0.750195% CI: [-16.46, 11.87]ANCOVA
Comparison: Days 1-2p-value: 0.081895% CI: [-23.94, 1.43]ANCOVA
Comparison: Days 1-2p-value: 0.003895% CI: [-33.18, -6.43]ANCOVA
Comparison: Days 1-2p-value: <0.000195% CI: [-40.75, 17.93]ANCOVA
Comparison: Days 1-2p-value: <0.000195% CI: [-37.59, -14.09]ANCOVA
Comparison: Days 14-15p-value: 0.464295% CI: [-9.6, 20.98]ANCOVA
Comparison: Days 14-15p-value: 0.775495% CI: [-18.27, 13.64]ANCOVA
Comparison: Days 14-15p-value: 0.146195% CI: [-25.14, 3.75]ANCOVA
Comparison: Days 14-15p-value: 0.058195% CI: [-29.97, 0.51]ANCOVA
Comparison: Days 14-15p-value: 0.001995% CI: [-33.86, -7.74]ANCOVA
Comparison: Days 14-15p-value: 0.00295% CI: [-35.12, -7.91]ANCOVA
Secondary
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
Time frame: Baseline up to Day 30
Population: The safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lemborexant 1 mg | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
| Lemborexant 2.5 mg | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
| Lemborexant 5 mg | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
| Lemborexant 10 mg | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
| Lemborexant 15 mg | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
| Lemborexant 25 mg | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
| Placebo | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs)
Time frame: Baseline up to Day 30
Population: The safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lemborexant 1 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
| Lemborexant 2.5 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
| Lemborexant 5 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
| Lemborexant 10 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
| Lemborexant 15 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
| Lemborexant 25 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
| Placebo | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) | 0 participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to Day 30
Population: The safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lemborexant 1 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Lemborexant 2.5 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Lemborexant 5 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Lemborexant 10 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Lemborexant 15 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Lemborexant 25 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Placebo | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time frame: TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days)
Population: The safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lemborexant 1 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 34.4 percentage of participants |
| Lemborexant 1 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 0 percentage of participants |
| Lemborexant 2.5 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 40.7 percentage of participants |
| Lemborexant 2.5 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 0 percentage of participants |
| Lemborexant 5 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 42.1 percentage of participants |
| Lemborexant 5 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 0 percentage of participants |
| Lemborexant 10 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 59.4 percentage of participants |
| Lemborexant 10 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 0 percentage of participants |
| Lemborexant 15 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 55.4 percentage of participants |
| Lemborexant 15 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 0 percentage of participants |
| Lemborexant 25 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 60.0 percentage of participants |
| Lemborexant 25 mg | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 2.0 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 37.5 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 1.8 percentage of participants |
Secondary
Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15
Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean LPS of Days 14-15 minus change from baseline of mean LPS of Days 1-2. LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep.
Time frame: Baseline and Days 1-2, and Days 14-15
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant 1 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | 2.71 minutes | Standard Deviation 24.333 |
| Lemborexant 2.5 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | -1.50 minutes | Standard Deviation 22.12 |
| Lemborexant 5 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | -4.60 minutes | Standard Deviation 22.337 |
| Lemborexant 10 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | -7.93 minutes | Standard Deviation 17.415 |
| Lemborexant 15 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | -1.11 minutes | Standard Deviation 24.568 |
| Lemborexant 25 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | 1.38 minutes | Standard Deviation 12.046 |
| Placebo | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15 | 0.57 minutes | Standard Deviation 40.855 |
Secondary
Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15
Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean SE of Days 14-15 minus change from baseline of mean SE of Days 1-2. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep.
Time frame: Baseline, Days 1-2, and Days 14-15
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant 1 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | -4.04 percentage of sleep time | Standard Deviation 8.194 |
| Lemborexant 2.5 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | -0.54 percentage of sleep time | Standard Deviation 10.505 |
| Lemborexant 5 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | 0.06 percentage of sleep time | Standard Deviation 6.888 |
| Lemborexant 10 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | -0.68 percentage of sleep time | Standard Deviation 6.883 |
| Lemborexant 15 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | -2.33 percentage of sleep time | Standard Deviation 6.6 |
| Lemborexant 25 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | -2.15 percentage of sleep time | Standard Deviation 5.388 |
| Placebo | Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15 | -1.05 percentage of sleep time | Standard Deviation 7.192 |
Secondary
Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15
Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean WASO of Days 14-15 minus change from baseline of mean WASO of Days 1-2. WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance.
Time frame: Baseline, Days 1-2, and Days 14-15
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant 1 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 17.98 minutes | Standard Deviation 34.299 |
| Lemborexant 2.5 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 2.16 minutes | Standard Deviation 44.054 |
| Lemborexant 5 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 2.68 minutes | Standard Deviation 29.726 |
| Lemborexant 10 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 9.30 minutes | Standard Deviation 25.89 |
| Lemborexant 15 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 11.76 minutes | Standard Deviation 26.187 |
| Lemborexant 25 mg | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 9.28 minutes | Standard Deviation 23.119 |
| Placebo | Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15 | 5.99 minutes | Standard Deviation 31.417 |
Secondary
Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17
Rebound insomnia was assessed by comparing the change from baseline of the mean SE on Days 16-17. Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. A negative change from baseline in SE indicated that SE was worse on Days 16 and 17 than at Baseline, which was considered as evidence for rebound insomnia.
Time frame: Baseline and Days 16-17
Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, number of participants analyzed (N) represents participants who were available for analysis at the specified timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant 1 mg | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 13.12 percentage of sleep time | Standard Error 1.661 |
| Lemborexant 2.5 mg | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 15.53 percentage of sleep time | Standard Error 1.777 |
| Lemborexant 5 mg | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 17.67 percentage of sleep time | Standard Error 1.535 |
| Lemborexant 10 mg | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 13.78 percentage of sleep time | Standard Error 1.653 |
| Lemborexant 15 mg | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 18.58 percentage of sleep time | Standard Error 1.253 |
| Lemborexant 25 mg | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 17.12 percentage of sleep time | Standard Error 1.374 |
| Placebo | Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 | 16.17 percentage of sleep time | Standard Error 1.28 |
Comparison: Days 16-17p-value: 0.148395% CI: [-7.2, 1.09]ANCOVA
Comparison: Days 16-17p-value: 0.77295% CI: [-4.96, 3.69]ANCOVA
Comparison: Days 16-17p-value: 0.454895% CI: [-2.44, 5.44]ANCOVA
Comparison: Days 16-17p-value: 0.25395% CI: [-6.51, 1.72]ANCOVA
Comparison: Days 16-17p-value: 0.179495% CI: [-1.11, 5.93]ANCOVA
Comparison: Days 16-17p-value: 0.614895% CI: [-2.74, 4.63]ANCOVA