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

A Study to Evaluate the Co-Administration of MK-4618 With Antihypertensive Agents

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: MK-4618; Drug: Placebo for MK-4618; Drug: Metoprolol; Drug: Amlodipine

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: MK-4618 + Met → PBO + Met; 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.	Drug: MK-4618; Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Placebo for MK-4618; Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Metoprolol; Previously prescribed daily dose of open-label metoprolol for the duration of the study; Other Names: Toprol-XL
Experimental: Panel A: PBO + Met → MK-4618 + Met; 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.	Drug: MK-4618; Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Placebo for MK-4618; Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Metoprolol; Previously prescribed daily dose of open-label metoprolol for the duration of the study; Other Names: Toprol-XL
Experimental: Panel B: MK-4618 + Amlo → PBO + Amlo; 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.	Drug: MK-4618; Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Placebo for MK-4618; Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Amlodipine; Previously prescribed daily dose of open-label amlodipine for the duration of the study; Other Names: Norvasc
Experimental: Panel B: PBO + Amlo → MK-4618 + Amlo; 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.	Drug: MK-4618; Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Placebo for MK-4618; Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7; Drug: Amlodipine; Previously prescribed daily dose of open-label amlodipine for the duration of the study; Other Names: Norvasc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Clinical or Laboratory Adverse Experience	An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product is also an adverse experience. The percentage of participants with a clinical or laboratory adverse experience was recorded.	Up to 42 days
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A	Semi-recumbent and standing systolic blood pressure was measured predose and at intervals up to 24 hours postdose on Day 1 and Day 7. The baseline value is the average of measurements taken in the hour before dosing. Participants were to rest quietly in a semi-recumbent position for at least 10 minutes before each semi-recumbent measurement.	Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B	Semi-recumbent and standing systolic blood pressure was measured predose and at intervals up to 24 hours postdose on Day 1 and Day 7. The baseline value is the average of measurements taken in the hour before dosing. Participants were to rest quietly in a semi-recumbent position for at least 10 minutes before each semi-recumbent measurement.	Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618	Blood samples were collected on Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose for the determination of plasma MK-4618 concentration. The hypothesis for this outcome is that the steady-state AUC0-24hr for MK-4618 is >=0.47 uM*hr.	Predose and up to 24 hours postdose on Day 7

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 15, 2011
• First Posted (Estimate): April 19, 2011

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 3, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Amlodipine; Metoprolol
• Other Study ID Numbers: 4618-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis