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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01337674
• Other study ID #: 4618-010
• Status: Completed
• Phase: Phase 1
• Start date: April 1, 2011
• Est. completion date: November 1, 2011

Study information

• Verified date: December 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 1, 2011
• Est. primary completion date: November 1, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• MK-4618
Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7
• Placebo for MK-4618
Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7
• Metoprolol
Previously prescribed daily dose of open-label metoprolol for the duration of the study
• Amlodipine
Previously prescribed daily dose of open-label amlodipine for the duration of the study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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