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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: Comparator: Amlodipine; Drug: Placebo; Drug: Comparator: ISMN ER

Study type: Interventional

Funder types: Industry

Identifiers

NCT01130168

2010_537

0000-166

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 30 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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38 participants in 6 patient groups

Placebo/ISMN ER/Amlodipine (Sequence 1)

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Amlodipine

Drug: Placebo

Drug: Comparator: ISMN ER

ISMN ER/Amlodipine/Placebo (Sequence 2)

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Amlodipine

Drug: Placebo

Drug: Comparator: ISMN ER

Amlodipine/Placebo/ISMN ER (Sequence 3)

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Amlodipine

Drug: Placebo

Drug: Comparator: ISMN ER

ISMN ER/Placebo/Amlodipine (Sequence 4)

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Amlodipine

Drug: Placebo

Drug: Comparator: ISMN ER

Placebo/Amlodipine/ISMN ER (Sequence 5)

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Amlodipine

Drug: Placebo

Drug: Comparator: ISMN ER

Amlodipine/ISMN ER/Placebo (Sequence 6)

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Amlodipine

Drug: Placebo

Drug: Comparator: ISMN ER