To Compare the Effectiveness of Suvorexant vs Placebo on Sleep Pressure in Hypertensives With Insomnia (Super1)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Insomnia
• Intervention / Treatment: Drug: suvorexant; Other: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Takahira Internal Medicine Clinic
  • Hyogo, Japan
    • Yamasaki Family Clinic
  • Tokyo, Japan
    • Yagi hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

[At interim registration]

Patients who meet the following criteria are eligible for the study:

1. Patients who give written consent of agreement to voluntarily participation in the clinical study
2. Age 20 years or older
3. Sex: Male or female
4. Treatment classification: Outpatient

5. Hypertensive patient who meet at least one of the following:

   • Under antihypertensive medications
   • Clinic systolic blood pressure (SBP) less than 160 mmHg

6. 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:

1. Stable unchanged antihypertensive medication for run-in period.
2. Average morning home SBP more than 135 mmHg during 5 days before the end of run-in period.

Exclusion Criteria:

1. Patients with serious liver disease.
2. Patients with serious respiratory disease.
3. Patients with secondary hypertension
4. Patients with sleep apnea syndrome
5. Patients with history of narcolepsy or cataplexy
6. Patients with history of organic cerebral disorders
7. Patients with history of hypersensitivity to suvorexant
8. Patients received CYP3A strongly-inhibitors including itraconazole, clarithromycin and ritonavir, saquinavir, nelfinavir, indinavir, telaprevir and voriconazole at the start of the run-in period
9. Patients with average clinic SBP of 160 mmHg or more at the start of the run-in period
10. Patients received suvorexant and other hypnotic at the start of the run-in period on a regular basis
11. Patients who are breast-feeding, pregnant, possibly pregnant, or plan to become pregnant
12. Patients who are considered not to be eligible for this study by their investigator or sub-investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jichi Medical University
• Collaborators: Merck Sharp & Dohme LLC; Satt Co.,Ltd
• Investigators: Principal Investigator: Kazuomi Kario, MD, PhD, Jichi Medical University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2017
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimate): July 29, 2016

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: June 16, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: 4305-063

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No