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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

April 15, 2011
December 22, 2015
April 2011
November 2011   (final data collection date for primary outcome measure)
  • 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.
  • Number of participants who experience clinical or laboratory adverse events [ Time Frame: Day 1 to 14 days following the last dose of study drug (approximately 60 days) ] [ Designated as safety issue: Yes ]
  • Change from baseline in systolic blood pressure [ Time Frame: Baseline and Day 1 ] [ Designated as safety issue: No ]
  • Change from baseline in systolic blood pressure [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01337674 on ClinicalTrials.gov Archive Site
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.
Steady-state area under the concentration versus time curve [AUC(0-24hr)] for MK-4618 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypertension
  • 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
  • Drug: Amlodipine
    Previously prescribed daily dose of open-label amlodipine for the duration of the study
    Other Name: Norvasc
  • 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.
    Interventions:
    • Drug: MK-4618
    • Drug: Placebo for MK-4618
    • Drug: Metoprolol
  • 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.
    Interventions:
    • Drug: MK-4618
    • Drug: Placebo for MK-4618
    • Drug: Metoprolol
  • 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.
    Interventions:
    • Drug: MK-4618
    • Drug: Placebo for MK-4618
    • Drug: Amlodipine
  • 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.
    Interventions:
    • Drug: MK-4618
    • Drug: Placebo for MK-4618
    • Drug: Amlodipine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
November 2011
November 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
United States
 
NCT01337674
4618-010
No
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP