A Phase Ib, Randomized, Double-Blind, 4-Treatment, 2-Period Incomplete Block Study to Evaluate the Multiple Dose Effects of MK-7145 and Hydrochlorothiazide Compared to Placebo on Blood Pressure in Male Patients With Hypertension
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 46
- Primary Endpoint
- Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1
Study Overview
Brief Summary
This study is being done to evaluate the antihypertensive efficacy and tolerability of MK-7145 in participants with mild-to-moderate hypertension.
The primary hypotheses for the study were as follows:
- Multiple dose administration of 6-mg MK-7145 results in a reduction in systolic blood pressure (SBP) in male participants with mild to moderate hypertension that is superior to placebo, as measured by time weighted average change from baseline over 24 hours postdose (TWA0-24hrs) on dosing Day 28
- Multiple dose administration of 6-mg MK-7145 results in a reduction in SBP in male participants with mild to moderate hypertension that is similar to hydrochlorothiazide (HCTZ), as measured by TWA0-24hrs on dosing Day 28
- The effect of MK-7145 and HCTZ on natriuresis (UNaV) as well as SBP and diastolic blood pressure (DBP), both as measured by TWA0-24hrs, will be estimated
- Multiple dose administration of MK-7145 for 4 weeks will be generally safe and well-tolerated.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
MK-7145 6 mg (Treatment A)
MK-7145 3 mg (three x 1-mg MK-7145 capsules administered orally) and placebo to HCTZ (two 12.5-mg capsules) then three x 1-mg MK-7145 capsules 4 hours later, daily for 4 weeks.
Intervention: MK-7145 (Drug)
MK-7145 6 mg (Treatment A)
MK-7145 3 mg (three x 1-mg MK-7145 capsules administered orally) and placebo to HCTZ (two 12.5-mg capsules) then three x 1-mg MK-7145 capsules 4 hours later, daily for 4 weeks.
Intervention: Placebo to HCTZ (Drug)
MK-7145 3 mg (Treatment B)
MK-7145 3 mg (one 2mg MK-7145 and one MK-7145 placebo capsule) then one 1-mg MK-7145 capsule and two MK-7145 placebo capsules 4 hours later and placebo to HCTZ (2 capsules once daily) daily for 4 weeks.
Intervention: MK-7145 (Drug)
MK-7145 3 mg (Treatment B)
MK-7145 3 mg (one 2mg MK-7145 and one MK-7145 placebo capsule) then one 1-mg MK-7145 capsule and two MK-7145 placebo capsules 4 hours later and placebo to HCTZ (2 capsules once daily) daily for 4 weeks.
Intervention: Placebo to MK-7145 (Drug)
MK-7145 3 mg (Treatment B)
MK-7145 3 mg (one 2mg MK-7145 and one MK-7145 placebo capsule) then one 1-mg MK-7145 capsule and two MK-7145 placebo capsules 4 hours later and placebo to HCTZ (2 capsules once daily) daily for 4 weeks.
Intervention: Placebo to HCTZ (Drug)
Hydrochlorothiazide 25 mg (Treatment C)
HCTZ 25 mg (two 12.5-mg capsules) and placebo to MK-7145 (one 3-mg capsule) then placebo for MK-7145 (one 3-mg capsule) 4 hours later daily for 4 weeks.
Intervention: Hydrochlorothiazide (HCTZ) (Drug)
Hydrochlorothiazide 25 mg (Treatment C)
HCTZ 25 mg (two 12.5-mg capsules) and placebo to MK-7145 (one 3-mg capsule) then placebo for MK-7145 (one 3-mg capsule) 4 hours later daily for 4 weeks.
Intervention: Placebo to MK-7145 (Drug)
Placebo (Treatment D)
Placebo to MK-7145 (2 x 3-mg capsules) and placebo to HCTZ 25 mg (2 capsules) then placebo to MK-7145 (2 x 3-mg capsules) 4 hours later daily for 4 weeks
Intervention: Placebo to MK-7145 (Drug)
Placebo (Treatment D)
Placebo to MK-7145 (2 x 3-mg capsules) and placebo to HCTZ 25 mg (2 capsules) then placebo to MK-7145 (2 x 3-mg capsules) 4 hours later daily for 4 weeks
Intervention: Placebo to HCTZ (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1
Time Frame: Baseline (Day-1) and Day 1
Urine sodium (Na) levels were measured over 24-hours on Day -1 (baseline) and on Day 1. The total amount of Na excreted in the urine for Day-1 (baseline) and Day1 were calculated and the difference between the 2 values was recorded.
Percentage of Participants Who Experienced at Least 1 Adverse Event (AE)
Time Frame: Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced an AE during the study was summarized by study drug taken at the time of the AE.
Percentage of Participants Who Had Study Discontinued During the Study Due to an Adverse Event (AE)
Time Frame: up to 4 weeks of each treatment period
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had the administration of the study drug discontinued during the study was summarized by study drug taken at the time of the AE. Participants may or may not have completed the study.
Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP)
Time Frame: Baseline and Day 28
Each participant had their blood pressure monitored by continuous 24-hour ambulatory blood pressure monitoring (ABPM) on Days -1 and 28 of each treatment period. The average systolic blood pressure over the 24-hour monitoring period was calculated for baseline (Day -1) and Day 28. The difference between baseline and Day 28 was calculated and recorded.
Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Diastolic Blood Pressure (DBP)
Time Frame: Baseline and Day 28
Each participant had their blood pressure monitored by continuous 24-hour ambulatory blood pressure monitoring (ABPM) on Days -1 and 28 of each treatment period. The average diastolic blood pressure over the 24-hour monitoring period was calculated for baseline (Day -1) and Day 28. The difference between baseline and Day 28 was calculated and recorded.
Percentage of Participants Who Experienced at Least 1 Drug-related Adverse Event (AE)
Time Frame: Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced an AE that was reported as at least possibly-related to the study was summarized by study drug taken at the time of the AE.
Secondary Outcomes
- Change From Baseline in Urine Potassium at 24 Hours Post-dose on Day 28(Baseline (Day -1) and Day 28)