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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01025843
First received: December 2, 2009
Last updated: January 28, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Hypertension
Drug: MK-5478
Drug: Comparator: Candesartan cilexetil
Drug: Comparator: Pbo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Single Dose Study to Evaluate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of MK5478 in Subjects and in Patients With Hypertension

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Treatment Due to an AE [ Time Frame: Up to 24 hours after administration of study drug ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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

  • Change From Baseline in Aortic Augmentation Index (AIx) of MK-5478 and Candesartan [ Time Frame: Baseline and 1 to 3 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Maximum Plasma Concentration (Cmax) of MK-5478 and Candesartan [ Time Frame: Pre-dose and up to 48 hours postdose ] [ Designated as safety issue: No ]
    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


Enrollment: 20
Study Start Date: December 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT01025843

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: NCT01025843     History of Changes
Other Study ID Numbers: 5478-001  2009-016048-38 
Study First Received: December 2, 2009
Results First Received: January 28, 2016
Last Updated: January 28, 2016
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Candesartan
Candesartan cilexetil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 30, 2016