Safety and Tolerability of MK-5478 in Participants With Hypertension (5478-001)
- Registration Number
- NCT01025843
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
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)
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pbo → 5 mg → Candesartan → 24 mg → 38 mg MK-5478 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. 2 mg→Pbo → Candesartan → Pbo fed→38 mg MK-5478 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. 2 mg → 8 mg → 18 mg → 2 mg fed → Pbo MK-5478 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. Candesartan→Pbo → 12 mg → 24 mg→38 mg MK-5478 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. 1 mg → Candesartan → Pbo → 24 mg → 38 mg MK-5478 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. Pbo→ 8 mg→ 18 mg → 2 mg fed→Candesartan MK-5478 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. Candesartan→8 mg→ 18 mg →2 mg fed→38 mg MK-5478 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. 1 mg → 5 mg → 12 mg → Pbo → Candesartan MK-5478 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. 1 mg → 5 mg → 12 mg → Candesartan → Pbo MK-5478 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. 2 mg→Candesartan→Pbo→Candesartan fed→38 mg MK-5478 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.
- Primary Outcome Measures
Name Time Method Number of Participants With One or More Adverse Events (AEs) 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.
Number of Participants Who Discontinued Treatment Due to an AE 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.
- Secondary Outcome Measures
Name Time Method Area Under the Plasma Concentration Versus Time Curve (AUC 0-infinity) of MK-5478 and Candesartan 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
Change From Baseline in Aortic Augmentation Index (AIx) of MK-5478 and Candesartan 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.
Maximum Plasma Concentration (Cmax) of MK-5478 and Candesartan 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