Primary Insomnia
Conditions
Brief summary
This is a multicenter study to test the hypothesis that suvorexant (MK-4305) is superior to placebo in improving insomnia as measured by change from baseline in: subjective total sleep time and time to sleep onset, wake time after persistent sleep onset, and latency to onset of persistent sleep.
Interventions
Suvorexant 40 mg + placebo matching suvorexant 20 mg for participants \<65 years old; Suvorexant 30 mg + placebo matching suvorexant 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month Treatment (TRT) Phase. During the 1-week double-blind (DB) Run-out (RO) following the TRT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.
Suvorexant 20 mg + placebo matching suvorexant 40 mg for participants \<65 years old; Suvorexant 15 mg + placebo matching suvorexant 30 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase. During the 1-week DB RO following the TRT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.
DRUGComparator: Placebo
Matching placebos to suvorexant 40 mg and 20 mg for participants \<65 years old; matching placebos to suvorexant 30 mg and 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Placebo is a third treatment arm for comparison to the two active (suvorexant) treatment arms during the 3-month TRT Phase. During the 1-week DB RO following the TRT phase, participants in this study arm continue to receive placebo. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be ≥18 yrs old on the day of signing informed consent * Diagnosed with Primary Insomnia * Good physical and mental health * Participant ≥65 yrs old score at least 25 on the Mini Mental State Examination * A female participant who is of reproductive potential has a negative serum pregnancy test and agrees to use contraception * Reports difficulty with initiating and maintaining sleep during the 4 weeks prior to Visit 1 (accordingly to specific protocol criteria) * Reports spending 6.5 to 9 hours nightly in bed on at least 3 out of 7 nights prior to Visit 1 * Regular bedtime is between 9 pm-1 am * Willing to refrain from napping while in study * Able to read, understand and complete questionnaires and all diaries * Willing to limit alcohol, caffeine, and nicotine consumption while in the study * For a portion of participants: Must be willing to stay overnight in a sleep laboratory and must be willing to stay in bed for at least 8 hours each night while at the sleep laboratory
Exclusion criteria
* Female participant is pregnant and/or breastfeeding at Prestudy visit, or expecting to conceive while in study * History or diagnosis of another sleep disorder * Difficulty sleeping due to a medical condition * History of a neurological disorder * History of bipolar disorder, psychotic disorder, or posttraumatic stress disorder, or current psychiatric disorder that requires a prohibited medication * Ongoing depression * History of substance abuse or dependence * History or current evidence of a clinically significant cardiovascular disorder or clinically significant electrocardiogram (ECG) at Prestudy Visit * Taking certain prohibited medications * Consumption of the equivalent of \>15 cigarettes a day * History of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer * Participant is considered morbidly obese * Previously randomized in another investigational study of suvorexant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinued Study Drug Due to an AE Occurring During 3-Month DB TRT Phase | Up to 3 months | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants who discontinued study drug treatment due to an AE occurring during the 3-month DB TRT Phase are counted once in this summary. |
| Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3 | Baseline and Month 3 | sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period. |
| Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1 | Baseline and Month 1 | LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment (Lights-Off) to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center. |
| Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3 | Baseline and Month 3 | LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment (Lights-Off) to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center. |
| Number of Participants With an Adverse Event (AE) During 3-Month DB TRT Phase | Up to 3 months | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants with an AE occurring during the 3-month DB TRT Phase are counted once in this summary. |
| Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1 | Baseline and Month 1 | sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily electronic diary (e-diary). Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any polysomnography \[PSG\] nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period. |
| Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3 | Baseline and Month 3 | sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period. |
| Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1 | Baseline and Month 1 | WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center. |
| Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3 | Baseline and Month 3 | WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center. |
| Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1 | Baseline and Month 1 | sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Suvorexant HD Versus Placebo: Change From Baseline in WASO at Night 1 | Baseline and Night 1 | WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center. |
| Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Week 1 | Baseline and Week 1 | sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period. |
| Suvorexant HD Versus Placebo: Change From Baseline in LPS at Night 1 | Baseline and Night 1 | LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment (Lights-Off) to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center. |
| Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Week 1 | Baseline and Week 1 | sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period. |
Participant flow
Pre-assignment details
A 2-week single-blind placebo Run-in occurred prior to randomization. 1 of the 1020 randomized participants enrolled in 2 separate suvorexant trials and is excluded from all summaries and analyses. 10 other randomized participants were not treated and are in Participant Flow Table below, but are excluded from all other summaries and analyses.
Participants by arm
| Arm | Count |
|---|---|
| Suvorexant LD After a 2-week single-blind placebo Run-in, participants received suvorexant LD (20 mg for participants aged 18 to \<65 years; and 15 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. | 239 |
| Suvorexant HD After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. | 387 |
| Placebo After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase. | 383 |
| Total | 1,009 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| DB RO Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| DB RO Phase | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 |
| DB RO Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Double-Blind (DB) Treatment (TRT) Phase | Adverse Event | 10 | 19 | 17 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment (TRT) Phase | Lack of Efficacy | 7 | 4 | 8 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment (TRT) Phase | Lost to Follow-up | 2 | 4 | 1 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment (TRT) Phase | Not Treated | 1 | 5 | 4 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment (TRT) Phase | Physician Decision | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment (TRT) Phase | Protocol Violation | 5 | 4 | 8 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment (TRT) Phase | Withdrawal by Subject | 8 | 9 | 19 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Suvorexant LD | Suvorexant HD | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 16 | 57 years STANDARD_DEVIATION 15 | 57 years STANDARD_DEVIATION 15 | 56 years STANDARD_DEVIATION 15 |
| Latency to Onset of Persistent Sleep (LPS) | 65.3 minutes STANDARD_DEVIATION 47.8 | 67.3 minutes STANDARD_DEVIATION 48.8 | 68.0 minutes STANDARD_DEVIATION 42.8 | 67.2 minutes STANDARD_DEVIATION 46.2 |
| Mean Subjective Time to Sleep Onset (sTSOm) | 86.0 minutes STANDARD_DEVIATION 77.6 | 74.4 minutes STANDARD_DEVIATION 61.9 | 81.3 minutes STANDARD_DEVIATION 76.2 | 79.8 minutes STANDARD_DEVIATION 71.5 |
| Mean Subjective Total Sleep Time (sTSTm) | 298.3 minutes STANDARD_DEVIATION 81.9 | 315.3 minutes STANDARD_DEVIATION 77 | 309.7 minutes STANDARD_DEVIATION 77.1 | 309.2 minutes STANDARD_DEVIATION 78.4 |
| Sex: Female, Male Female | 157 Participants | 267 Participants | 247 Participants | 671 Participants |
| Sex: Female, Male Male | 82 Participants | 120 Participants | 136 Participants | 338 Participants |
| Wakefulness After Persistent Sleep Onset (WASO) | 119.6 minutes STANDARD_DEVIATION 50.8 | 119.4 minutes STANDARD_DEVIATION 51.3 | 118.4 minutes STANDARD_DEVIATION 49.1 | 119.0 minutes STANDARD_DEVIATION 50.3 |
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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 239 | 59 / 387 | 33 / 383 | 0 / 97 | 1 / 108 | 4 / 173 | 1 / 171 | 4 / 327 | 0 / 239 | 2 / 387 | 0 / 383 | 0 / 97 | 1 / 108 | 0 / 173 | 0 / 171 | 1 / 327 |
| serious Total, serious adverse events | 2 / 239 | 6 / 387 | 5 / 383 | 0 / 97 | 1 / 108 | 0 / 173 | 0 / 171 | 0 / 327 | 0 / 239 | 1 / 387 | 0 / 383 | 0 / 97 | 0 / 108 | 0 / 173 | 0 / 171 | 0 / 327 |
Outcome results
Primary
Number of Participants Who Discontinued Study Drug Due to an AE Occurring During 3-Month DB TRT Phase
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants who discontinued study drug treatment due to an AE occurring during the 3-month DB TRT Phase are counted once in this summary.
Time frame: Up to 3 months
Population: All Patients as Treated (APaT) population, consisting of all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant HD | Number of Participants Who Discontinued Study Drug Due to an AE Occurring During 3-Month DB TRT Phase | 9 participants |
| Placebo | Number of Participants Who Discontinued Study Drug Due to an AE Occurring During 3-Month DB TRT Phase | 18 participants |
| Placebo | Number of Participants Who Discontinued Study Drug Due to an AE Occurring During 3-Month DB TRT Phase | 17 participants |
Primary
Number of Participants With an Adverse Event (AE) During 3-Month DB TRT Phase
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants with an AE occurring during the 3-month DB TRT Phase are counted once in this summary.
Time frame: Up to 3 months
Population: All Patients as Treated (APaT) population, consisting of all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant HD | Number of Participants With an Adverse Event (AE) During 3-Month DB TRT Phase | 103 participants |
| Placebo | Number of Participants With an Adverse Event (AE) During 3-Month DB TRT Phase | 189 participants |
| Placebo | Number of Participants With an Adverse Event (AE) During 3-Month DB TRT Phase | 167 participants |
Primary
Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1
LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment (Lights-Off) to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time frame: Baseline and Month 1
Population: Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1 | -36.7 minutes | 95% Confidence Interval 46.5 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1 | -24.6 minutes | 95% Confidence Interval 43.3 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 LPS, had planned marginal power of 81.4%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: 0.0000495% CI: [-17.8, -6.4]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3
LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment (Lights-Off) to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time frame: Baseline and Month 3
Population: Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3 | -32.2 minutes | 95% Confidence Interval 47.6 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3 | -28.6 minutes | 95% Confidence Interval 44 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 LPS, had planned marginal power of 76.2%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: 0.265195% CI: [-10.1, 2.8]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1
sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time frame: Baseline and Month 1
Population: Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1 | -26.9 minutes | 95% Confidence Interval 62.8 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1 | -14.1 minutes | 95% Confidence Interval 77.8 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 sTSOm, had planned marginal power of 99.9%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: 0.0000395% CI: [-18.8, -6.9]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1
sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily electronic diary (e-diary). Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any polysomnography \[PSG\] nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time frame: Baseline and Month 1
Population: Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1 | 48.7 minutes | 95% Confidence Interval 77.4 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1 | 22.4 minutes | 95% Confidence Interval 77.6 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 sTSTm, had planned marginal power of 97.6%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [18.3, 34.3]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3
sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time frame: Baseline and Month 3
Population: Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3 | -33.7 minutes | 95% Confidence Interval 62.4 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3 | -20.5 minutes | 95% Confidence Interval 66.1 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 sTSOm, had planned marginal power of 99.6%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: 0.0000395% CI: [-19.4, -7]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3
sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time frame: Baseline and Month 3
Population: Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3 | 62.8 minutes | 95% Confidence Interval 75.9 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3 | 37.7 minutes | 95% Confidence Interval 71.8 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 sTSTm, had planned marginal power of 95.7%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [16, 34.2]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1
WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time frame: Baseline and Month 1
Population: Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1 | -51.9 minutes | 95% Confidence Interval 51.2 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1 | -22.5 minutes | 95% Confidence Interval 49.3 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 WASO, had planned marginal power of 99.2%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [-36.6, -22.3]Longitudinal Data Analysis
Primary
Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3
WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time frame: Baseline and Month 3
Population: Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3 | -54.2 minutes | 95% Confidence Interval 51.1 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3 | -24.8 minutes | 95% Confidence Interval 49.6 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 WASO, had planned marginal power of 98.3%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [-36.7, -22.1]Longitudinal Data Analysis
Secondary
Suvorexant HD Versus Placebo: Change From Baseline in LPS at Night 1
LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment (Lights-Off) to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time frame: Baseline and Night 1
Population: Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in LPS at Night 1 | -34.7 minutes | 95% Confidence Interval 24.2 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in LPS at Night 1 | -13.0 minutes | 95% Confidence Interval 60.8 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Night 1 LPS, had planned marginal power of 100.0%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [-28.6, -14.9]Longitudinal Data Analysis
Secondary
Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Week 1
sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time frame: Baseline and Week 1
Population: Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Week 1 | -19.7 minutes | 95% Confidence Interval 59 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Week 1 | -6.7 minutes | 95% Confidence Interval 76 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Week 1 sTSOm, had planned marginal power of 99.6%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [-17.7, -8.4]Longitudinal Data Analysis
Secondary
Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Week 1
sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time frame: Baseline and Week 1
Population: Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Week 1 | 40.4 minutes | 95% Confidence Interval 83.1 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Week 1 | 14.0 minutes | 95% Confidence Interval 81 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Week 1 sTSTm, had planned marginal power of 98.3%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [19.8, 33.1]Longitudinal Data Analysis
Secondary
Suvorexant HD Versus Placebo: Change From Baseline in WASO at Night 1
WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment (Lights-Off) is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording (Lights-On). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time frame: Baseline and Night 1
Population: Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant HD | Suvorexant HD Versus Placebo: Change From Baseline in WASO at Night 1 | -63.3 minutes | 95% Confidence Interval 37.5 |
| Placebo | Suvorexant HD Versus Placebo: Change From Baseline in WASO at Night 1 | -21.3 minutes | 95% Confidence Interval 65.5 |
Comparison: The null hypothesis, that suvorexant HD did not differ from placebo for Night 1 WASO, had planned marginal power of 100.0%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.p-value: <0.0000195% CI: [-48.6, -35.3]Longitudinal Data Analysis