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

NCT01337674 | Completed Phase 1 Results

• 1 other identifier: 4618-010
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618

  Predose and up to 24 hours postdose on Day 7

Study Arms (4)

Panel A: MK-4618 + Met → PBO + Met

EXPERIMENTAL

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

Panel A: PBO + Met → MK-4618 + Met

EXPERIMENTAL

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

Panel B: MK-4618 + Amlo → PBO + Amlo

EXPERIMENTAL

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

Panel B: PBO + Amlo → MK-4618 + Amlo

EXPERIMENTAL

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

Interventions

MK-4618 DRUG

Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7

Panel A: MK-4618 + Met → PBO + Met; Panel A: PBO + Met → MK-4618 + Met; Panel B: MK-4618 + Amlo → PBO + Amlo; Panel B: PBO + Amlo → MK-4618 + Amlo

Placebo for MK-4618 DRUG

Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7

Panel A: MK-4618 + Met → PBO + Met; Panel A: PBO + Met → MK-4618 + Met; Panel B: MK-4618 + Amlo → PBO + Amlo; Panel B: PBO + Amlo → MK-4618 + Amlo

Metoprolol DRUG

Previously prescribed daily dose of open-label metoprolol for the duration of the study

Also known as: Toprol-XL

Panel A: MK-4618 + Met → PBO + Met; Panel A: PBO + Met → MK-4618 + Met

Amlodipine DRUG

Previously prescribed daily dose of open-label amlodipine for the duration of the study

Also known as: Norvasc

Panel B: MK-4618 + Amlo → PBO + Amlo; Panel B: PBO + Amlo → MK-4618 + Amlo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Interventions

N-(4-((5-(hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4-oxo-4,6,7,8-tetrahydropyrrolo(1,2-a)pyrimidine-6-carboxamide; Metoprolol; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme, Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2011
• First Posted: April 19, 2011
• Study Start: April 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 24, 2018
• Results First Posted: February 2, 2016

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share