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

• Sponsor: Jichi Medical University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02849184
• Collaborator: Merck Sharp & Dohme LLC (Industry), Satt Co.,Ltd (Other)
• Enrollment: 82
• Locations: 3
• Arms: 2
• Actual Duration (Months): 13.4
• Patients Per Site: 27.3
• Patients Per Site Per Month: 2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Insomnia	Drug: suvorexant; Other: Placebo	Phase 4

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jan 17, 2017
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. 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

4. 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).

5. Change in Urinary Albumin-to-creatinine Ratio (UACR) [2 weeks]

   Percentage change in UACR from baseline to 2 weeks

6. 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).

7. Change in NT-proBNP [2 weeks]

   Percentage change in NT-proBNP from baseline to 2 weeks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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).

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Takahira Internal Medicine Clinic	Fukuoka		Japan
2	Yamasaki family clinic	Hyogo		Japan
3	Yagi hospital	Tokyo		Japan

Sponsors and Collaborators

• Jichi Medical University
• Merck Sharp & Dohme LLC
• Satt Co.,Ltd

Investigators

• Principal Investigator: Kazuomi Kario, MD, PhD, Jichi Medical University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 10, 2016

More Information

Publications

None provided.

• Responsible Party: Kazuomi Kario, Professor & Chairman, Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University
• ClinicalTrials.gov Identifier: NCT02849184
• Other Study ID Numbers: 4305-063
• First Posted: Jul 29, 2016
• Last Update Posted: Aug 5, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Suvorexant

Study Results

Participant Flow

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Period Title: Overall Study
STARTED	40	42
COMPLETED	40	42
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Suvorexant	Placebo	Total
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.	Total of all reporting groups
Overall Participants	40	42	82
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (12.1)	55.9 (9.5)	56.6 (10.8)
Sex: Female, Male (Count of Participants)
Female	11 27.5%	13 31%	24 29.3%
Male	29 72.5%	29 69%	58 70.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.5 (4.4)	25.9 (3.9)	25.7 (4.1)
Nighttime systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	137.9 (15.9)	140.7 (18.1)	139.4 (17.0)
Nighttime diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	80.5 (8.7)	84.2 (10.2)	82.4 (9.6)

Outcome Measures

1. Primary Outcome

Title	Change in Sleep Systolic Blood Pressure
Description	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
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	40	42
Mean (Standard Error) [mmHg]	-1.8 (2.7)	-4.4 (2.7)

2. Secondary Outcome

Title	Change in Morning Systolic Blood Pressure Variability
Description	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
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	40	42
Mean (Standard Error) [mmHg]	-0.3 (1.5)	0.8 (1.5)

3. Secondary Outcome

Title	Changes in the Total Sleep Time
Description	Total sleep time was assessed using a sleep diary. Value at week 2 - Value at week 0
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	40	42
Mean (Standard Error) [hours]	0.51 (0.24)	0.43 (0.25)

4. Secondary Outcome

Title	Changes in the Time to Sleep Onset
Description	Time to sleep onset was assessed using a sleep diary. Value at week 2 - Value at week 0
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	40	42
Mean (Standard Error) [hours]	-0.23 (0.18)	-0.42 (0.15)

5. Secondary Outcome

Title	Change in Nighttime SBP in Patients Achieved High Sleep Satisfaction
Description	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).
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Patients who were satisfied with sleep as of 2 weeks

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	24	17
Mean (Standard Error) [mmHg]	-6.1 (3.5)	3.1 (4.2)

6. Secondary Outcome

Title	Change in Urinary Albumin-to-creatinine Ratio (UACR)
Description	Percentage change in UACR from baseline to 2 weeks
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	40	42
Median (95% Confidence Interval) [percentage change]	1.50	-13.12

7. Secondary Outcome

Title	Change in Nighttime SBP in Patients Achieved Low Sleep Satisfaction
Description	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).
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Patients who were not satisfied with sleep as of 2 weeks

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	16	25
Mean (Standard Error) [mmHg]	4.5 (3.9)	-9.5 (3.1)

8. Secondary Outcome

Title	Change in NT-proBNP
Description	Percentage change in NT-proBNP from baseline to 2 weeks
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.	Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
Measure Participants	40	42
Median (95% Confidence Interval) [percentage change]	3.65	-2.80

Adverse Events

Time Frame	14 months
Arm/Group Title	Suvorexant		Placebo
Arm/Group Description	Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) in oral administration, once daily before bedtime; Treatment duration: 2 weeks suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.		Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks. Placebo: Placebo once daily before bedtime.
All Cause Mortality
	Suvorexant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/42 (0%)
Serious Adverse Events
	Suvorexant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Suvorexant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/42 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.