Primary Insomnia
Conditions
Brief summary
This was a cross-over, polysomnography (PSG) study to test the safety, tolerability and effectiveness of different doses of MK-6096 in the treatment of participants with primary insomnia. The primary efficacy hypothesis was that at least one dose of MK-6096 is superior to placebo in improving sleep efficiency (SE) as measured by PSG on Night 1 and at the end of 4 weeks of treatment (Week 4).
Interventions
DRUGMK-6096
MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.
DRUGDose-matched Placebo to MK-6096
Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Participant is willing to stay overnight at a sleep laboratory on 6 separate nights and is willing to stay in bed for at least 8 hours each night while at the sleep laboratory * Participant's regular bedtime is between 9 PM and 12 AM (midnight) * Participant is able to read and complete questionnaires and diaries * Participant is willing to refrain from napping during the study
Exclusion criteria
* If female, participant is breast feeding, pregnant, or planning to become pregnant * Participant is expecting to donate eggs or sperm during the study * Participant has any history of a neurological disorder * Participant has a history within the past 6 months of a cardiovascular disorder such as unstable angina, congestive heart failure or acute coronary syndrome. * Participant has difficulty sleeping due to a medical condition * Participant has donated blood products within the 8 weeks prior to the study * Participant plans to travel across 3 or more time zones during the study * Participant is currently participating or has participated in a study with an investigational compound or device within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Night 1 and end of Week 4 | SE was measured using a polysomnogram (PSG), which consisted of an electroencephalogram (EEG) for registration of brain activity during sleep, an electro-oculogram (EOG) for registration of the eye movements during sleep, and an electromyogram (EMG) for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to Rechtschaffen and Kales (R&K) criteria and PSG data were read by a Central Reader. SE was defined as total sleep time (TST) in minutes divided by time in bed (measured from lights off to lights on; fixed at 8 hours on each PSG night) in minutes, multiplied by 100, where TST is defined as the total time (minutes) in Stages 1, 2, 3, 4 and Rapid Eye Movement (REM). SE= (total sleep time/time in bed) x 100. Least squares (LS) mean SE was reported for each treatment arm. |
| Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2 | Day 1 through Day 29 in Treatment Periods 1 and 2 (58 days total) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. The percentage of participants with AEs are presented for the first day of randomized treatment dosing (Day 1) through the last day of randomized treatment dosing (Day 29) in Treatment Periods 1 and 2. |
| Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2 | Day 1 through Day 29 in Treatment Periods 1 and 2 (58 days total) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. The percentage of participants that discontinued study medication due to AEs are presented for the first day of randomized treatment dosing (Day 1) through the last day of randomized treatment dosing (Day 29) in Treatment Periods 1 and 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Night 1 and end of Week 4 | WASO was measured using a PSG, which consisted of an EEG for registration of brain activity during sleep, an EOG for registration of the eye movements during sleep, and an EMG for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to R&K criteria and PSG data were read by a Central Reader. WASO was defined as the duration of wakefulness measured in minutes (any epoch of Stage 0) from persistent sleep onset (first epoch of the first twenty consecutive epochs of non-wake) to lights on. LS mean WASO was reported for each treatment arm. |
| Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Night 1 and end of Week 4 | LPS was measured using a PSG, which consisted of an EEG for registration of brain activity during sleep, an EOG for registration of the eye movements during sleep, and an EMG for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to R&K criteria and PSG data were read by a Central Reader. LPS was defined as the duration of time measured in minutes from lights off to persistent sleep onset. An epoch of non-wake was defined as a 30-second interval classified as either Stage 1, 2, 3, 4 or REM according to conventional R&K scoring. LS mean LPS was reported for each treatment arm. |
Participant flow
Pre-assignment details
326 participants were randomized in this study into one of 8 treatment sequences. Participants received double-blind study drug in Treatment Period (TP)1, followed by a washout period (3 day single-blind placebo plus 11 day drug holiday), and then double-blind study drug in TP2.
Participants by arm
| Arm | Count |
|---|---|
| MK-6096 2.5 mg/Placebo Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 2.5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for overnight polysomnography (PSG) recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment for the remaining 11 days. During Treatment Period 2, participants receive dose-matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime. | 40 |
| Placebo/MK-6096 2.5 mg Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment for the remaining 11 days. During Treatment Period 2, participants receive MK-6096 2.5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime. | 40 |
| MK-6096 5 mg/Placebo Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for 2 overnight PSG recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo to MK-6096 for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime. | 41 |
| Placebo/MK-6096 5 mg Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive MK-6096 5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime. | 40 |
| MK-6096 10 mg/Placebo Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 10 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for 2 overnight PSG recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo to MK-6096 for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime. | 42 |
| Placebo/MK-6096 10 mg Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive MK-6096 10 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime. | 41 |
| MK-6096 20 mg/Placebo Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 20 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for 2 overnight PSG recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo to MK-6096 for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime. | 41 |
| Placebo/MK-6096 20 mg Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive MK-6096 20 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime. | 41 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 3 | 1 | 1 | 0 | 2 | 2 | 0 | 0 |
| Treatment Period 1 | Not Treated | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Pregnancy | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Treatment Period 2 | Adverse Event | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 |
| Treatment Period 2 | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 2 | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Washout Period-No Drug | Adverse Event | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout Period-Placebo | Adverse Event | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Washout Period-Placebo | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Washout Period-Placebo | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | MK-6096 2.5 mg/Placebo | Placebo/MK-6096 2.5 mg | MK-6096 5 mg/Placebo | Placebo/MK-6096 5 mg | MK-6096 10 mg/Placebo | Placebo/MK-6096 10 mg | MK-6096 20 mg/Placebo | Placebo/MK-6096 20 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 46.9 years STANDARD_DEVIATION 11.9 | 47.9 years STANDARD_DEVIATION 11.7 | 44.7 years STANDARD_DEVIATION 10.7 | 47.6 years STANDARD_DEVIATION 10.4 | 45.4 years STANDARD_DEVIATION 9.9 | 45.2 years STANDARD_DEVIATION 11 | 49.8 years STANDARD_DEVIATION 9.8 | 47.0 years STANDARD_DEVIATION 12.3 | 46.8 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 25 Participants | 25 Participants | 26 Participants | 25 Participants | 26 Participants | 26 Participants | 25 Participants | 25 Participants | 203 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 16 Participants | 15 Participants | 16 Participants | 16 Participants | 123 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 | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 315 | 3 / 79 | 5 / 78 | 10 / 80 | 14 / 81 | 5 / 315 | 0 / 324 |
| serious Total, serious adverse events | 0 / 315 | 1 / 79 | 1 / 78 | 1 / 80 | 0 / 81 | 1 / 315 | 1 / 324 |
Outcome results
Primary
Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. The percentage of participants that discontinued study medication due to AEs are presented for the first day of randomized treatment dosing (Day 1) through the last day of randomized treatment dosing (Day 29) in Treatment Periods 1 and 2.
Time frame: Day 1 through Day 29 in Treatment Periods 1 and 2 (58 days total)
Population: APaT population; all randomized participants who received at least one dose of study treatment. Participants were included corresponding to the study treatment they actually received for a given period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2 | 2.2 percentage of participants |
| MK-6096 2.5 mg | Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2 | 5.1 percentage of participants |
| MK-6096 5 mg | Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2 | 1.3 percentage of participants |
| MK-6096 10 mg | Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2 | 2.5 percentage of participants |
| MK-6096 20 mg | Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2 | 0.0 percentage of participants |
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-1, 10.2]
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-3.6, 4.8]
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-2.7, 6.6]
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-4.5, 2.3]
Primary
Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. The percentage of participants with AEs are presented for the first day of randomized treatment dosing (Day 1) through the last day of randomized treatment dosing (Day 29) in Treatment Periods 1 and 2.
Time frame: Day 1 through Day 29 in Treatment Periods 1 and 2 (58 days total)
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment. Participants were included corresponding to the study treatment they actually received for a given period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2 | 26.0 percentage of participants |
| MK-6096 2.5 mg | Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2 | 26.6 percentage of participants |
| MK-6096 5 mg | Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2 | 25.6 percentage of participants |
| MK-6096 10 mg | Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2 | 32.5 percentage of participants |
| MK-6096 20 mg | Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2 | 34.6 percentage of participants |
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-9.5, 12.2]
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-10.3, 11.2]
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-4.2, 18.3]
Comparison: Miettinen and Nurminen's method was used to calculate confidence intervals for between-treatment differences in the percentage of participants with events versus placebo.95% CI: [-2.3, 20.4]
Primary
Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment
SE was measured using a polysomnogram (PSG), which consisted of an electroencephalogram (EEG) for registration of brain activity during sleep, an electro-oculogram (EOG) for registration of the eye movements during sleep, and an electromyogram (EMG) for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to Rechtschaffen and Kales (R&K) criteria and PSG data were read by a Central Reader. SE was defined as total sleep time (TST) in minutes divided by time in bed (measured from lights off to lights on; fixed at 8 hours on each PSG night) in minutes, multiplied by 100, where TST is defined as the total time (minutes) in Stages 1, 2, 3, 4 and Rapid Eye Movement (REM). SE= (total sleep time/time in bed) x 100. Least squares (LS) mean SE was reported for each treatment arm.
Time frame: Night 1 and end of Week 4
Population: Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization SE efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 74.8 percentage of time in bed spent sleeping | Standard Error 0.71 |
| Placebo | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 77.0 percentage of time in bed spent sleeping | Standard Error 0.71 |
| MK-6096 2.5 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 83.3 percentage of time in bed spent sleeping | Standard Error 1.54 |
| MK-6096 2.5 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 81.6 percentage of time in bed spent sleeping | Standard Error 1.42 |
| MK-6096 5 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 84.8 percentage of time in bed spent sleeping | Standard Error 1.55 |
| MK-6096 5 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 81.1 percentage of time in bed spent sleeping | Standard Error 1.42 |
| MK-6096 10 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 86.7 percentage of time in bed spent sleeping | Standard Error 1.43 |
| MK-6096 10 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 85.6 percentage of time in bed spent sleeping | Standard Error 1.53 |
| MK-6096 20 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 88.2 percentage of time in bed spent sleeping | Standard Error 1.53 |
| MK-6096 20 mg | Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 85.7 percentage of time in bed spent sleeping | Standard Error 1.43 |
Comparison: MK-6096 2.5 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [5.3, 11.5]Mixed Models Analysis
Comparison: MK-6096 5 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [6.8, 13.1]Mixed Models Analysis
Comparison: MK-6096 10 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [7.7, 13.8]Mixed Models Analysis
Comparison: MK-6096 20 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [10.3, 16.5]Mixed Models Analysis
Comparison: MK-6096 2.5 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.00195% CI: [1.8, 7.4]Mixed Models Analysis
Comparison: MK-6096 5 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.00495% CI: [1.3, 6.9]Mixed Models Analysis
Comparison: MK-6096 10 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [6.9, 12.5]Mixed Models Analysis
Comparison: MK-6096 20 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [5.9, 11.5]Mixed Models Analysis
Secondary
Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment
LPS was measured using a PSG, which consisted of an EEG for registration of brain activity during sleep, an EOG for registration of the eye movements during sleep, and an EMG for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to R&K criteria and PSG data were read by a Central Reader. LPS was defined as the duration of time measured in minutes from lights off to persistent sleep onset. An epoch of non-wake was defined as a 30-second interval classified as either Stage 1, 2, 3, 4 or REM according to conventional R&K scoring. LS mean LPS was reported for each treatment arm.
Time frame: Night 1 and end of Week 4
Population: FAS population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization LPS efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 43.4 minutes | Standard Error 2.06 |
| Placebo | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 39.4 minutes | Standard Error 2.19 |
| MK-6096 2.5 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 33.2 minutes | Standard Error 4.35 |
| MK-6096 2.5 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 30.5 minutes | Standard Error 4.55 |
| MK-6096 5 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 27.7 minutes | Standard Error 4.36 |
| MK-6096 5 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 30.7 minutes | Standard Error 4.55 |
| MK-6096 10 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 19.9 minutes | Standard Error 4.57 |
| MK-6096 10 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 19.9 minutes | Standard Error 4.32 |
| MK-6096 20 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 23.0 minutes | Standard Error 4.31 |
| MK-6096 20 mg | Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 28.1 minutes | Standard Error 4.58 |
Comparison: MK-6096 2.5 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.02295% CI: [-18.9, -1.5]Mixed Models Analysis
Comparison: MK-6096 5 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-24.5, -7]Mixed Models Analysis
Comparison: MK-6096 10 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-32.1, -14.9]Mixed Models Analysis
Comparison: MK-6096 20 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-29, -11.7]Mixed Models Analysis
Comparison: MK-6096 2.5 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.05595% CI: [-18, 0.2]Mixed Models Analysis
Comparison: MK-6096 5 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.0695% CI: [-17.8, 0.4]Mixed Models Analysis
Comparison: MK-6096 10 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-28.6, -10.4]Mixed Models Analysis
Comparison: MK-6096 20 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.01595% CI: [-20.5, -2.2]Mixed Models Analysis
Secondary
Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment
WASO was measured using a PSG, which consisted of an EEG for registration of brain activity during sleep, an EOG for registration of the eye movements during sleep, and an EMG for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to R&K criteria and PSG data were read by a Central Reader. WASO was defined as the duration of wakefulness measured in minutes (any epoch of Stage 0) from persistent sleep onset (first epoch of the first twenty consecutive epochs of non-wake) to lights on. LS mean WASO was reported for each treatment arm.
Time frame: Night 1 and end of Week 4
Population: FAS population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization WASO efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 83.1 minutes | Standard Error 2.81 |
| Placebo | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 76.1 minutes | Standard Error 2.77 |
| MK-6096 2.5 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 52.3 minutes | Standard Error 6.11 |
| MK-6096 2.5 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 60.6 minutes | Standard Error 5.62 |
| MK-6096 5 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 50.6 minutes | Standard Error 6.14 |
| MK-6096 5 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 62.9 minutes | Standard Error 5.62 |
| MK-6096 10 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 50.5 minutes | Standard Error 5.63 |
| MK-6096 10 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 52.2 minutes | Standard Error 6.06 |
| MK-6096 20 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Night 1 (n=313, 79, 78, 80, 80) | 37.3 minutes | Standard Error 6.07 |
| MK-6096 20 mg | Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment | Week 4 (n=300, 76, 76, 76, 75) | 46.1 minutes | Standard Error 5.65 |
Comparison: MK-6096 2.5 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-43.2, -18.4]Mixed Models Analysis
Comparison: MK-6096 5 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-44.9, -20.1]Mixed Models Analysis
Comparison: MK-6096 10 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-43.2, -18.7]Mixed Models Analysis
Comparison: MK-6096 20 mg vs. Placebo at Night 1~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Night 1. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-58, -33.5]Mixed Models Analysis
Comparison: MK-6096 2.5 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.00695% CI: [-26.7, -4.4]Mixed Models Analysis
Comparison: MK-6096 5 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: 0.0295% CI: [-24.4, -2.1]Mixed Models Analysis
Comparison: MK-6096 10 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-36.8, -14.5]Mixed Models Analysis
Comparison: MK-6096 20 mg vs. Placebo at Week 4~A mixed effects model with terms for baseline value, geographic region (Japan vs. ex-Japan), gender, treatment, sequence, period, time, and treatment-by-time interaction and period-by-time interaction was used to estimate LS mean differences between MK-6096 and placebo at Week 4. 95% confidence interval estimate and p-value (based upon a normal approximation) were also computed from the LS mean differences and variability estimates from the model.p-value: <0.00195% CI: [-41.2, -18.8]Mixed Models Analysis