A Single Dose Study to Evaluate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of MK5478 in Subjects and in Patients With Hypertension
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 20
- Primary Endpoint
- Number of Participants With One or More Adverse Events (AEs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Is a male between 18 to 50 years of age
- •Is in good health
- •Is a non-smoker
- •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
Arms & Interventions
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
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.
Intervention: MK-5478 (Drug)
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- Area Under the Plasma Concentration Versus Time Curve (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(Baseline and 1 to 3 hours postdose)
- Maximum Plasma Concentration (Cmax) of MK-5478 and Candesartan(Pre-dose and up to 48 hours postdose)