To Compare the Effectiveness of Suvorexant vs Placebo on Sleep Pressure in Hypertensives With Insomnia

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of suvorexant versus placebo on sleep pressure and circadian rhythm in hypertensives with insomnia.

Detailed Description
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The study consists of a 4-week run-in period and a 2-week treatment period.

Official Title
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A Multi-center, Double-blind, Randomized, Parallel Design Study to Compare the Effectiveness of Suvorexant Versus Placebo on Sleep Pressure and Circadian Rhythm in Hypertensives With Insomnia: The Super 1 Study

Conditions
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Hypertension, Insomnia

Intervention / Treatment
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* Drug: suvorexant
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: [At interim registration] Patients who meet the following criteria are eligible for the study: Patients who give written consent of agreement to voluntarily participation in the clinical study Age 20 years or older Sex: Male or female Treatment classification: Outpatient Hypertensive patient who meet at least one of the following: Under antihypertensive medications Clinic systolic blood pressure (SBP) less than 160 mmHg Patients with insomnia who meet at least one of the following: Patients with any one of the following symptoms twice a week or more and at least 1 month-continuation: difficulty initiating sleep (time to sleep onset 2 hours or more longer than usual), difficulty maintaining sleep (awakening twice or more in the night), early morning awakening (awakening 2 hours or more earlier in the morning than usual), difficulty sleeping deeply (no soundly asleep feeling at the time of awakening in the morning). b. Patients with interference with social or occupational function due to the above insomnia symptoms [At official registration] Patients who meet the following criteria at the end of run-in period are eligible for the study: Stable unchanged antihypertensive medication for run-in period. Average morning home SBP more than 135 mmHg during 5 days before the end of run-in period. Exclusion Criteria: Patients with serious liver disease. Patients with serious respiratory disease. Patients with secondary hypertension Patients with sleep apnea syndrome Patients with history of narcolepsy or cataplexy Patients with history of organic cerebral disorders Patients with history of hypersensitivity to suvorexant Patients received CYP3A strongly-inhibitors including itraconazole, clarithromycin and ritonavir, saquinavir, nelfinavir, indinavir, telaprevir and voriconazole at the start of the run-in period Patients with average clinic SBP of 160 mmHg or more at the start of the run-in period Patients received suvorexant and other hypnotic at the start of the run-in period on a regular basis Patients who are breast-feeding, pregnant, possibly pregnant, or plan to become pregnant Patients who are considered not to be eligible for this study by their investigator or sub-investigator

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: suvorexant<br>Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks | Drug: suvorexant<br>* Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.<br>* Other names: Belsomra;|
| Placebo Comparator: placebo<br>Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. | Other: Placebo<br>* Placebo once daily before bedtime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sleep Systolic Blood Pressure | To compare the efficacy of suvorexant versus placebo on sleep systolic blood pressure (SBP) by ambulatory blood pressure monitoring (ABPM). Change: sleep SBP value at 2 weeks minus value at baseline | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Morning Systolic Blood Pressure Variability | To compare the efficacy of suvorexant versus placebo on morning SBP variability by ABPM Variability: SD Change: value at 2 weeks minus value at baseline | 2 weeks | 
| Changes in the Total Sleep Time | Total sleep time was assessed using a sleep diary. Value at week 2 - Value at week 0 | 2 weeks | 
| Changes in the Time to Sleep Onset | Time to sleep onset was assessed using a sleep diary. Value at week 2 - Value at week 0 | 2 weeks | 
| Change in Nighttime SBP in Patients Achieved High Sleep Satisfaction | nighttime BPs are measured by ambulatory blood pressure monitoring. Sleep quality is measured by self-reported sleep diary (satisfaction level of sleep) at 2 weeks. Patients are divided by sleep satisfaction and compared nighttime SBP change (value at 2 weeks minus value at baseline). | 2 weeks | 
| Change in Urinary Albumin-to-creatinine Ratio (UACR) | Percentage change in UACR from baseline to 2 weeks | 2 weeks | 
| Change in Nighttime SBP in Patients Achieved Low Sleep Satisfaction | nighttime BPs are measured by ambulatory blood pressure monitoring. Sleep quality is measured by self-reported sleep diary (satisfaction level of sleep) at 2weeks. Patients are divided by sleep satisfaction and compared nighttime SBP change (value at 2 weeks minus value at baseline). | 2 weeks | 
| Change in NT-proBNP | Percentage change in NT-proBNP from baseline to 2 weeks | 2 weeks |