Co-Administration of MK-4618 With Antihypertensive Agents (MK-4618-010)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: Placebo for MK-4618; Drug: MK-4618; Drug: Amlodipine; Drug: Metoprolol

Study type: Interventional

Funder types: Industry

Identifiers

NCT01337674

4618-010

Details and patient eligibility

About

This study will evaluate the safety and tolerability of MK-4618 when coadministered with antihypertensive agents and will evaluate changes in blood pressure following co-administration of MK-4618 with a beta blocker and a vasodilator. The primary hypothesis of the study is that MK-4618 does not result in a clinically meaningful change in systolic blood pressure relative to placebo when co-administered with a beta-blocker or with amlodipine.

Enrollment: 26 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female not of childbearing potential
• Not a nursing mother
• Must be on stable dose of a beta blocker (Panel A only) or amlodipine (Panel B only) for the treatment of hypertension for at least 6 weeks prior to enrollment. Must take the designated daily dose of metoprolol or amlodipine for the duration of the study
• In good health other than hypertension
• Nonsmoker
• Participant has a resting systolic blood pressure <150 and >95 mmHg and a diastolic blood pressure <95 and >75 mmHg at prestudy clinical evaluation

Exclusion criteria

• Any illness that might confound the results of the study or pose a risk by participation
• History of orthostatic hypotension (decrease in blood pressure upon standing accompanied by symptoms of lightheadedness or dizziness)
• History of cancer, excepting certain skin or cervical cancers or cancers that were treated successfully 10 or more years prior to screening
• Condition for which there is a warning, contraindication, or precaution against the use of extended release metoprolol (Panel A) or amlodipine (Panel B)
• Consumes excessive amounts of alcohol or caffeine daily
• Has multiple and/or severe allergies (including latex allergy) or has had an anaphylactic reaction or significant intolerance to drugs or food
• Uses illicit drugs or has a history of drug abuse

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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26 participants in 4 patient groups

Panel A: MK-4618 + Met → PBO + Met

Experimental group

Description:

Once daily oral dose of MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 1 followed by once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of metoprolol (Met) for the duration of the study. A 2-week washout period follows Period 1.

Treatment:

Drug: Metoprolol

Drug: MK-4618

Drug: Placebo for MK-4618

Panel A: PBO + Met → MK-4618 + Met

Experimental group

Description:

Once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 1 followed by MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of metoprolol (Met) for the duration of the study. A 2-week washout period follows Period 1.

Treatment:

Drug: Metoprolol

Drug: MK-4618

Drug: Placebo for MK-4618

Panel B: MK-4618 + Amlo → PBO + Amlo

Experimental group

Description:

Once daily oral dose of MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 1 followed by once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of amlodipine (Amlo) for the duration of the study. A 2-week washout period follows Period 1.

Treatment:

Drug: Amlodipine

Drug: MK-4618

Drug: Placebo for MK-4618

Panel B: PBO + Amlo → MK-4618 + Amlo

Experimental group

Description:

Once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 1 followed by MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of amlodipine (Amlo) for the duration of the study. A 2-week washout period follows Period 1.

Treatment:

Drug: Amlodipine

Drug: MK-4618

Drug: Placebo for MK-4618