Safety and Tolerability of MK5478 in Patients With Hypertension (5478-001)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01025843
First received: December 2, 2009
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

This is a two part introductory clinical trial with MK5478. Part I will evaluate pharmacokinetics and pharmacodynamics of MK5478 in young healthy male subjects. Part II will evaluate the safety, tolerability and pharmacodynamic effects of MK5478 in patients with hypertension.


Condition Intervention Phase
Hypertension
Drug: MK5478
Drug: Comparator: Candesartan cilexetil
Drug: Comparator: Pbo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy 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:
  • safety and tolerability of a single oral dose of MK5478 based on assessment of clinical and laboratory adverse experiences [ Time Frame: 14 days after administration of last dose of study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC 0-infinity) of MK5478 [ Time Frame: baseline and 4 hours postdose ] [ Designated as safety issue: No ]
  • Aortic Augmentation Index (AIx) [ Time Frame: baseline and 1 to 3 hours postdose ] [ Designated as safety issue: No ]
  • Cmax of MK5478 [ Time Frame: baseline and 4 hours postdose ] [ Designated as safety issue: No ]

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: Part 1A - Sequence 1
Pbo - 5 mg - Candesartan - 100 mg - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1A- Sequence 2
1 mg - 5 mg - 20 mg - Candesartan - Pbo
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1A- Sequence 3
1 mg - Candesartan - Pbo - 100 mg - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1A - Sequence 4
1 mg - 5 mg - 20 mg - Pbo - Candesartan
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1B - Sequence 1
Pbo - 10 mg - 50 mg - 10 mg - Candesartan
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1B - Sequence 2
2 mg - Pbo - Candesartan - Pbo - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1B - Sequence 3
2 mg - Candesartan - Pbo - Candesartan - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1B - Sequence 4
2 mg - 10 mg - 50 mg - 10 mg - Pbo
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1B - Sequence 5
Candesartan - 10 mg - 50 mg - 10 mg - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 1A - Sequence 5
Candesartan - Pbo - 20 mg - 100 mg - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 2C - Sequence 1
20 mg - Pbo - 100 mg - 200 mg - Candesartan
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 2C - Sequence 2
20 mg - 50 mg - Pbo - Candesartan - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 2C - Sequence 3
Candesartan - 50 mg - 100 mg - 200 mg - Pbo
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 2C - Sequence 4
20 mg - Candesartan - 100 mg - Pbo - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 mg.
Drug: Comparator: Candesartan cilexetil
single dose administration of candesartan, 32 mg oral tablet
Other Name: Atacand/Amias
Drug: Comparator: Pbo
Placebo
Experimental: Part 2C - Sequence 5
Pbo - 50 mg - Candesartan - 200 mg - 200 mg
Drug: MK5478
In Part I: Single dose administration of MK5478 oral capsules, total doses of 1, 2, 5, 10, 20, 50, 100 or 200 mg. In Part II: Single dose administration of MK5478 oral capsules, total doses of 20, 50 100 or 200 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 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Part I:

  • Subject is a male between 18 to 45 years of age
  • Subject is in good health
  • Subject is a non-smoker

Part II:

  • Patient is male of female of non-child bearing potential between 18 and 55 years of age
  • Patient has hypertension (high blood pressure)

Exclusion Criteria:

Part I and Part II:

  • Subject has a history of stroke, seizures or major neurological disorder
  • Subject has a history of cancer
  • Subject has a history of any cardiovascular disease
  • Subject is unable to refrain from the use of any prescription or non-prescription drugs
  • Subject consumes excessive amounts of alcohol or caffeine
  • Subject 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 Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT01025843     History of Changes
Other Study ID Numbers: 2009_702, MK5478-001
Study First Received: December 2, 2009
Last Updated: January 27, 2011
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

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

ClinicalTrials.gov processed this record on August 21, 2014