The Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Participants and Participants With Hypertension (MK-0000-166) (COMPLETED)

Merck Sharp & Dohme LLC38 enrolled

Overview

This study will test the relationship between CBP (central blood pressure) and PBP (peripheral blood pressure) effects after single and multiple doses of Isosorbide mononitrate extended release (ISMN ER) or Amlodipine besylate in participants with hypertension.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hypertension

Interventions

PlaceboDRUG

Placebo, capsule taken orally once daily during 4 weeks of treatment

Comparator: AmlodipineDRUG

Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks

Comparator: ISMN ERDRUG

ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks

Eligibility

Sex: ALLMin age: 30 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Participant is a male or female between 30 and 65 years of age (inclusive) at the pre-study (screening) * Female participant of childbearing potential must have a negative pregnancy test * Participant has a brachial systolic blood pressure \>130 mm Hg and \<180 mm Hg * Participant has a Body Mass Index (BMI) that is \>20 kg/m\^2 and \<35 kg/m\^2 * Participant has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months Exclusion Criteria: * Female Participant is pregnant or lactating * Participant anticipates the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) other than acetaminophen * Participant is currently a user (including "recreational use") of any illicit drugs, has a history of drug or alcohol abuse within approximately 2 years, or has a positive prestudy urine drug screen * Participant has a condition for which there is a warning, contraindication, or precaution against the use of ISMN ER including: acute myocardial infarction or congestive heart failure, hypotension, volume depletion, and pregnancy * Participant has a history of significant drug allergy or any clinically significant adverse experience of a serious nature related to the administration of either a marketed or an investigational drug, including nitrates, nitrites, Amlodipine, and ISMN ER

Outcomes

Primary Outcomes

Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment

The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Single dose effects on AIx were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.

Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)

Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment

The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.

Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose

TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment

Central SBP was measured by the SphygmoCor® device. Single dose effects on central SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.

Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)

Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment

Central SBP was measured by the SphygmoCor® device. Central SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.

Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose

Data from ClinicalTrials.gov

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