Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study A (MK-4305-028)

Study Overview
=================
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. Participants who complete the initial 3-month Treatment (TRT) Phase may participate in an optional 3-month Extension (EXT) Phase.

Official Title
-----------------
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of MK-4305 in Patients With Primary Insomnia - Study A

Conditions
-----------------
Primary Insomnia

Intervention / Treatment
-----------------
* Drug: Suvorexant High Dose (HD)
* Drug: Suvorexant Low Dose (LD)
* Drug: Comparator: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suvorexant HD<br>Drug | Drug: Suvorexant High Dose (HD)<br>* 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 TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week double-blind (DB) Run-out (RO) following the TRT/EXT 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.<br>* Other names: MK-4305;|
| Experimental: Suvorexant LD<br>Drug | Drug: Suvorexant Low Dose (LD)<br>* 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 and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT 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.<br>* Other names: MK-4305;|
| Placebo Comparator: Placebo<br>Placebo Comparator | Drug: Comparator: Placebo<br>* 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 and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Month 1 | 
| 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. | Baseline and Month 3 | 
| 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. | Baseline and Month 1 | 
| 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. | Baseline and Month 3 | 
| 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. | Baseline and Month 1 | 
| 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. | Baseline and Month 3 | 
| 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. | Baseline and Month 1 | 
| 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. | Baseline and Month 3 | 
| Number of Participants With an Adverse Event (AE) During Initial 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 initial 3-month DB TRT Phase are counted once in this summary. | Up to 3 months | 
| Number of Participants Who Discontinued Study Drug Due to an AE Occurring During Initial 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 initial 3-month DB TRT Phase are counted once in this summary. | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Suvorexant LD/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. | Baseline and Week 1 | 
| Suvorexant LD Versus Placebo: Change From Baseline in 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 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. | Baseline and Month 1 | 
| Suvorexant LD 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. | Baseline and Month 3 | 
| Suvorexant LD/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. | Baseline and Night 1 | 
| Suvorexant LD Versus Placebo: Change From Baseline in 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. | Baseline and Month 1 | 
| Suvorexant LD 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. | Baseline and Month 3 | 
| Suvorexant LD/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. | Baseline and Week 1 | 
| Suvorexant LD Versus Placebo: Change From Baseline in 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. | Baseline and Month 1 | 
| Suvorexant LD 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. | Baseline and Month 3 | 
| Suvorexant LD/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. | Baseline and Night 1 | 
| Suvorexant LD Versus Placebo: Change From Baseline in 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. | Baseline and Month 1 | 
| Suvorexant LD 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. | Baseline and Month 3 |