Safety and Tolerability of MK-5478 in Participants With Hypertension (5478-001)

August 22, 2018 updated by: Merck Sharp & Dohme LLC

A Single Dose Study to Evaluate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of MK5478 in Subjects and in Patients With Hypertension

This is a two part introductory clinical trial with MK-5478. Part I will evaluate the safety, tolerability and pharmacokinetics and pharmacodynamics of MK-5478 in young, healthy males. Part II will evaluate the safety, tolerability and pharmacodynamic effects of MK-5478 in participants with hypertension. The primary hypothesis is that single oral doses of MK-5478 are sufficiently safe and well tolerated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

Part I:

  • Is a male between 18 to 50 years of age
  • Is in good health
  • Is a non-smoker

Part II:

  • Is male of non-child bearing potential between 18 and 50 years of age
  • Has hypertension (high blood pressure)

Exclusion Criteria:

Part I and Part II:

  • Has a history of stroke, seizures or major neurological disorder
  • Has a history of cancer
  • Has a history of any cardiovascular disease
  • Is unable to refrain from the use of any prescription or non-prescription drugs
  • Consumes excessive amounts of alcohol or caffeine
  • Has had major surgery, donated blood or participated in another investigational study in the past 4 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pbo → 5 mg → Candesartan → 24 mg → 38 mg
Placebo in Period 1; 5 mg MK-5478 in Period 2; Candesartan in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: 1 mg → 5 mg → 12 mg → Candesartan → Pbo
1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Candesartan in Period 4; and Placebo in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: 1 mg → Candesartan → Pbo → 24 mg → 38 mg
1 mg MK-5478 in Period 1; Candesartan in Period 2: Placebo in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: 1 mg → 5 mg → 12 mg → Pbo → Candesartan
1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Placebo in Period 4; and Candesartan in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Pbo→ 8 mg→ 18 mg → 2 mg fed→Candesartan
Placebo in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Candesartan in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: 2 mg→Pbo → Candesartan → Pbo fed→38 mg
2 mg MK-5478 in Period 1; Placebo in Period 2; Candesartan in Period 3; Placebo in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: 2 mg→Candesartan→Pbo→Candesartan fed→38 mg
2 mg MK-5478 in Period 1; Candesartan in Period 2; Placebo in Period 3; Candesartan in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: 2 mg → 8 mg → 18 mg → 2 mg fed → Pbo
2 mg MK-5478 in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Placebo in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Candesartan→8 mg→ 18 mg →2 mg fed→38 mg
Candesartan in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Candesartan→Pbo → 12 mg → 24 mg→38 mg
Candesartan in Period 1; Placebo in Period 2; 12 mg MK-5478 in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Drug: MK-5478
In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.
Drug: Comparator: Candesartan cilexetil
Single dose administration of candesartan, 32 mg oral tablet
Other Names:
  • Atacand/Amias
Drug: Comparator: Pbo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With One or More Adverse Events (AEs)
Time Frame: Up to 14 days after administration of last dose of study drug (up to Day 52)
An AE is 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Up to 14 days after administration of last dose of study drug (up to Day 52)
Number of Participants Who Discontinued Treatment Due to an AE
Time Frame: Up to 24 hours after administration of study drug
An AE is 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Up to 24 hours after administration of study drug

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration Versus Time Curve (AUC 0-infinity) of MK-5478 and Candesartan
Time Frame: Pre-dose and up to 48 hours postdose
Blood was collected at the following time points: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours post-dose in order to measure AUC 0-infinity of MK-5478 and Candesartan
Pre-dose and up to 48 hours postdose
Change From Baseline in Aortic Augmentation Index (AIx) of MK-5478 and Candesartan
Time Frame: Baseline and 1 to 3 hours postdose
Central blood pressure (CBP) parameters will be measured and used to derive the aortic augmentation index (AIx). The AIx quantifies the contribution of back-reflected outgoing systolic pressure waves to late-systolic central blood pressure, which increases with decreasing aortic compliance. AIx is measured by pulse wave analysis using the SphygmoCor System supplied by AtCor Medical. Results with a > 5% decrease in AIx were planned for analysis; results with a < 5% decrease in AIx were not analysed.
Baseline and 1 to 3 hours postdose
Maximum Plasma Concentration (Cmax) of MK-5478 and Candesartan
Time Frame: Pre-dose and up to 48 hours postdose
Blood was collected at the following time points: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours post-dose in order to measure the Cmax of MK-5478 and Candesartan
Pre-dose and up to 48 hours postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 4, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 21, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5478-001
  • 2009-016048-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

  1. CSR Synopsis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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