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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01130168
First received: May 19, 2010
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Placebo
Drug: Comparator: Amlodipine
Drug: Comparator: ISMN ER
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled, 3-Period, Crossover Study to Evaluate the Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Subjects and Patients With Hypertension

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline (0 hrs), 12 hours post-dose (Day 1) ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment [ Time Frame: Baseline (0 hrs), 24 hours after the Day 28 dose ] [ Designated as safety issue: No ]

    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.


  • TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment [ Time Frame: Baseline (0 hrs), 12 hours post-dose (Day 1) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment [ Time Frame: Baseline (0 hrs), 24 hours after the Day 28 dose ] [ Designated as safety issue: No ]
    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.

  • TWA Change From Baseline (0 Hours) to 12 Hours in Central Diastolic Blood Pressure (DBP) After A Single Dose of Treatment [ Time Frame: Baseline (0 hrs), 12 hours post-dose (Day 1) ] [ Designated as safety issue: No ]
    Central DBP was measured by the SphygmoCor® device. Single dose effects on central DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.

  • Change From Baseline (0 Hours) to Week 4 in Central DBP After Multiple Doses of Treatment [ Time Frame: Baseline (0 hrs), 24 hours after the Day 28 dose ] [ Designated as safety issue: No ]
    Central DBP was measured by the SphygmoCor® device. Central DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.

  • TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral SBP After A Single Dose of Treatment [ Time Frame: Baseline (0 hrs), 12 hours post-dose (Day 1) ] [ Designated as safety issue: No ]
    Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.

  • Change From Baseline (0 Hours) to Week 4 in Peripheral SBP After Multiple Doses of Treatment [ Time Frame: Baseline (0 hrs), 24 hours after the Day 28 dose ] [ Designated as safety issue: No ]
    Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.

  • TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral DBP After A Single Dose of Treatment [ Time Frame: Baseline (0 hrs), 12 hours post-dose (Day 1) ] [ Designated as safety issue: No ]
    Peripheral DBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.

  • Change From Baseline (0 Hours) to Week 4 in Peripheral DBP After Multiple Doses of Treatment [ Time Frame: Baseline (0 hrs), 24 hours after the Day 28 dose ] [ Designated as safety issue: No ]
    Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.


Enrollment: 38
Study Start Date: May 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo/ISMN ER/Amlodipine (Sequence 1)
Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
Drug: Placebo
Placebo, capsule taken orally once daily during 4 weeks of treatment
Drug: Comparator: Amlodipine
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Drug: Comparator: ISMN ER
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks
Experimental: ISMN ER/Amlodipine/Placebo (Sequence 2)
Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
Drug: Placebo
Placebo, capsule taken orally once daily during 4 weeks of treatment
Drug: Comparator: Amlodipine
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Drug: Comparator: ISMN ER
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks
Experimental: Amlodipine/Placebo/ISMN ER (Sequence 3)
Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
Drug: Placebo
Placebo, capsule taken orally once daily during 4 weeks of treatment
Drug: Comparator: Amlodipine
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Drug: Comparator: ISMN ER
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks
Experimental: ISMN ER/Placebo/Amlodipine (Sequence 4)
Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
Drug: Placebo
Placebo, capsule taken orally once daily during 4 weeks of treatment
Drug: Comparator: Amlodipine
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Drug: Comparator: ISMN ER
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks
Experimental: Placebo/Amlodipine/ISMN ER (Sequence 5)
Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
Drug: Placebo
Placebo, capsule taken orally once daily during 4 weeks of treatment
Drug: Comparator: Amlodipine
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Drug: Comparator: ISMN ER
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks
Experimental: Amlodipine/ISMN ER/Placebo (Sequence 6)
Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule for 4 weeks during Period, with a 2-week washout between each period.
Drug: Placebo
Placebo, capsule taken orally once daily during 4 weeks of treatment
Drug: Comparator: Amlodipine
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Drug: Comparator: ISMN ER
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks

  Eligibility

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01130168

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01130168     History of Changes
Other Study ID Numbers: 0000-166, 2010_537
Study First Received: May 19, 2010
Results First Received: February 23, 2012
Last Updated: October 25, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Amlodipine
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on April 17, 2014