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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

December 2, 2009
January 28, 2016
December 2009
May 2010   (final data collection date for primary outcome measure)
  • 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.
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 ]
Complete list of historical versions of study NCT01025843 on ClinicalTrials.gov Archive Site
  • 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
  • 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 ]
Not Provided
Not Provided
 
Safety and Tolerability of MK-5478 in Participants With Hypertension (5478-001)
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.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypertension
  • 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 → 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
  • 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.
    Interventions:
    • Drug: MK-5478
    • Drug: Comparator: Candesartan cilexetil
    • Drug: Comparator: Pbo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
May 2010
May 2010   (final data collection date for primary outcome measure)

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
Male
18 Years to 50 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
Belgium
 
NCT01025843
5478-001, 2009-016048-38
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.
January 2016

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