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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01337674
Recruitment Status : Completed
First Posted : April 19, 2011
Results First Posted : February 2, 2016
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: MK-4618 Drug: Placebo for MK-4618 Drug: Metoprolol Drug: Amlodipine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Co-Administration of MK-4618 With Antihypertensive Agents
Actual Study Start Date : April 1, 2011
Actual Primary Completion Date : November 1, 2011
Actual Study Completion Date : November 1, 2011


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 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




Primary Outcome Measures :
  1. Percentage of Participants With a Clinical or Laboratory Adverse Experience [ Time Frame: Up to 42 days ]
    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.

  2. 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 ]
    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.

  3. 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 ]
    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 :
  1. 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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01337674


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
Study Data/Documents: CSR Synopsis  This link exits the ClinicalTrials.gov site

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01337674    
Other Study ID Numbers: 4618-010
First Posted: April 19, 2011    Key Record Dates
Results First Posted: February 2, 2016
Last Update Posted: December 24, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Metoprolol
Amlodipine
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Anti-Arrhythmia Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents