Hypertension, Insomnia
Conditions
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.
Interventions
DRUGsuvorexant
Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime.
OTHERPlacebo
Placebo once daily before bedtime.
Sponsors
Merck Sharp & Dohme LLC
Satt Co.,Ltd
Jichi Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 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 |
| 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). |
| Change in NT-proBNP | 2 weeks | Percentage change in NT-proBNP from baseline to 2 weeks |
| Change in Urinary Albumin-to-creatinine Ratio (UACR) | 2 weeks | Percentage change in UACR from baseline to 2 weeks |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
suvorexant: Suvorexant (20mg for 64 years or younger; 15mg for 65 years or older) once daily before bedtime. | 40 |
| Placebo Placebo in oral administration, once daily before bedtime; Treatment duration: 2 weeks.
Placebo: Placebo once daily before bedtime. | 42 |
| Total | 82 |
Baseline characteristics
| Characteristic | Placebo | Total | Suvorexant |
|---|---|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 9.5 | 56.6 years STANDARD_DEVIATION 10.8 | 57.3 years STANDARD_DEVIATION 12.1 |
| BMI | 25.9 kg/m^2 STANDARD_DEVIATION 3.9 | 25.7 kg/m^2 STANDARD_DEVIATION 4.1 | 25.5 kg/m^2 STANDARD_DEVIATION 4.4 |
| Nighttime diastolic blood pressure | 84.2 mmHg STANDARD_DEVIATION 10.2 | 82.4 mmHg STANDARD_DEVIATION 9.6 | 80.5 mmHg STANDARD_DEVIATION 8.7 |
| Nighttime systolic blood pressure | 140.7 mmHg STANDARD_DEVIATION 18.1 | 139.4 mmHg STANDARD_DEVIATION 17 | 137.9 mmHg STANDARD_DEVIATION 15.9 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 13 Participants | 24 Participants | 11 Participants |
| Sex: Female, Male Male | 29 Participants | 58 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 42 |
| other Total, other adverse events | 0 / 40 | 0 / 42 |
| serious Total, serious adverse events | 0 / 40 | 0 / 42 |
Outcome results
Primary
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
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Change in Sleep Systolic Blood Pressure | -1.8 mmHg | Standard Error 2.7 |
| Placebo | Change in Sleep Systolic Blood Pressure | -4.4 mmHg | Standard Error 2.7 |
Secondary
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
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Change in Morning Systolic Blood Pressure Variability | -0.3 mmHg | Standard Error 1.5 |
| Placebo | Change in Morning Systolic Blood Pressure Variability | 0.8 mmHg | Standard Error 1.5 |
Secondary
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).
Time frame: 2 weeks
Population: Patients who were satisfied with sleep as of 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Change in Nighttime SBP in Patients Achieved High Sleep Satisfaction | -6.1 mmHg | Standard Error 3.5 |
| Placebo | Change in Nighttime SBP in Patients Achieved High Sleep Satisfaction | 3.1 mmHg | Standard Error 4.2 |
Secondary
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).
Time frame: 2 weeks
Population: Patients who were not satisfied with sleep as of 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Change in Nighttime SBP in Patients Achieved Low Sleep Satisfaction | 4.5 mmHg | Standard Error 3.9 |
| Placebo | Change in Nighttime SBP in Patients Achieved Low Sleep Satisfaction | -9.5 mmHg | Standard Error 3.1 |
Secondary
Change in NT-proBNP
Percentage change in NT-proBNP from baseline to 2 weeks
Time frame: 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant | Change in NT-proBNP | 3.65 percentage change |
| Placebo | Change in NT-proBNP | -2.80 percentage change |
Secondary
Change in Urinary Albumin-to-creatinine Ratio (UACR)
Percentage change in UACR from baseline to 2 weeks
Time frame: 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant | Change in Urinary Albumin-to-creatinine Ratio (UACR) | 1.50 percentage change |
| Placebo | Change in Urinary Albumin-to-creatinine Ratio (UACR) | -13.12 percentage change |
Secondary
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
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Changes in the Time to Sleep Onset | -0.23 hours | Standard Error 0.18 |
| Placebo | Changes in the Time to Sleep Onset | -0.42 hours | Standard Error 0.15 |
Secondary
Changes in the Total Sleep Time
Total sleep time was assessed using a sleep diary. Value at week 2 - Value at week 0
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Changes in the Total Sleep Time | 0.51 hours | Standard Error 0.24 |
| Placebo | Changes in the Total Sleep Time | 0.43 hours | Standard Error 0.25 |