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

Phase 4

Completed

Brief Summary: 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: The study consists of a 4-week run-in period and a 2-week treatment period.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks.
suvorexant	suvorexant	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks

Primary Outcome Measures

Name	Time	Method
Change in Sleep Systolic Blood Pressure	2 weeks	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

Secondary Outcome Measures

Name	Time	Method
Changes in the Total Sleep Time	2 weeks	Total sleep time was assessed using a sleep diary. Value at week 2 - Value at week 0
Change in Urinary Albumin-to-creatinine Ratio (UACR)	2 weeks	Percentage change in UACR from baseline to 2 weeks
Change in Morning Systolic Blood Pressure Variability	2 weeks	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
Changes in the Time to Sleep Onset	2 weeks	Time to sleep onset was assessed using a sleep diary. Value at week 2 - Value at week 0
Change in NT-proBNP	2 weeks	Percentage change in NT-proBNP from baseline to 2 weeks
Change in Nighttime SBP in Patients Achieved High Sleep Satisfaction	2 weeks	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).
Change in Nighttime SBP in Patients Achieved Low Sleep Satisfaction	2 weeks	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).