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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01337674
First received: April 15, 2011
Last updated: December 22, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Hypertension
Drug: MK-4618
Drug: Placebo for MK-4618
Drug: Metoprolol
Drug: Amlodipine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Co-Administration of MK-4618 With Antihypertensive Agents

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With a Clinical or Laboratory Adverse Experience [ Time Frame: Up to 42 days ] [ Designated as safety issue: Yes ]
    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.

  • Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A [ Time Frame: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7 ] [ Designated as safety issue: No ]
    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.

  • Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B [ Time Frame: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618 [ Time Frame: Predose and up to 24 hours postdose on Day 7 ] [ Designated as safety issue: No ]
    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.


Enrollment: 26
Study Start Date: April 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: Norvasc

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01337674

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01337674     History of Changes
Other Study ID Numbers: 4618-010 
Study First Received: April 15, 2011
Results First Received: October 30, 2015
Last Updated: December 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amlodipine
Metoprolol
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Anti-Arrhythmia Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 27, 2016