A Study of the Pharmacokinetics and Pharmacodynamics of MK1809 (1809-001)(COMPLETED)

Study Overview
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Brief Summary
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The goal of this study is to identify at least one safe and well tolerated dose of MK1809 that has similar pharmacokinetic qualities as 100 mg losartan.

Official Title
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A Double-Blind, Double Dummy, Randomized, Placebo-Controlled, Alternating Panel, Single Oral Rising Dose Study to Assess the Pharmacokinetics and Pharmacodynamics of MK1809 in Healthy Young Volunteers

Conditions
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Hypertension

Intervention / Treatment
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* Drug: MK1809
* Drug: Comparator: Losartan
* Drug: Comparator: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Nonsmoker for at least 6 months Body Mass Index (BMI) less than or equal to 29 kg/m2 In overall good health Part 2: Body Mass Index (BMI) greater than 18kg/m2 and less than or equal to 35kg/m2 In overall good health (patients with hypertension and/or hyperlipidemia are accepted) Exclusion Criteria: Part 1: History of any cardiovascular disease or any clinically significant family history of cardiac arrhythmias or conduction abnormalities at an age less than 60 years History of any major endocrine, vascular, hematologic, gastrointestinal, hepatic, renal or genitourinary disease/disorder History of cancer Clinically significant history of a neurological disorder (includes epilepsy,stroke, transient ischemic attack, classic migraines) Active or history of a psychiatric disorder (includes depression, bipolar disorder, schizophrenia, anxiety) History of asthma, severe wheezing, COPD, or other pulmonary disease Individual or family history of bleeding or hemorrhagic diathesis, or bleeding difficulties Major surgery, donated blood or participated in another investigational drug(s) trial within 30 days Illicit drug use (including recreational); or history of drug or alcohol abuse (within 2 years) Nitrate therapy within 4 weeks History of significant drug allergy or history of food allergies Part 2 History of any clinically significant cardiac or cardiovascular disease (other than hypertension) History of any major endocrine, vascular, hematologic, gastrointestinal, hepatic, renal or genitourinary disease/disorder History of cancer History of a neurological disorder (includes epilepsy,stroke, transient ischemic attack, classic migraines) Active or history of a psychiatric disorder (includes depression, bipolar disorder, schizophrenia, anxiety) History of asthma, severe wheezing, COPD, or other pulmonary disease Individual or family history of bleeding or hemorrhagic diathesis, or bleeding difficulties Illicit drug use (including recreational); or history of drug or alcohol abuse (within 2 years) Surgery, significant blood loss, donated blood, or participated in another investigational drug(s) trial within 30 days Nitrate therapy within 4 weeks History of significant drug allergy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 A-1<br>Part 1; Panel A; Sequence 1: 2 mg MK1809 / placebo / 50 mg MK1809 / 150 mg MK1809 / 100 mg Losartan | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 A-2<br>Part 1; Panel A; Sequence 2: Losartan / 10 mg MK1809 / placebo / 150 mg MK1809 / 280 mg MK1809 | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 A-3<br>Part 1; Panel A; Sequence 3 2 mg MK1809 / 10 mg MK1809 / Losartan / Placebo / 280 mg MK1809 | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 A-4<br>Part 1; Panel A; Sequence 4 2 mg MK1809 / Losartan / 50 mg MK1809 / 150 mg MK1809 / Placebo | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 A-5<br>Part 1; Panel A; Sequence 5: Placebo / 10 mg MK1809 / 50 mg MK1809 / Losartan / 280 mg MK1809 | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 B-1<br>Part 1; Panel B; Sequence 1: 5 mg MK1809 / Placebo / 100 mg MK1809 / 210 mg MK1809 / Placebo with food | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 B-2<br>Part 1; Panel B; Sequence 2: 5 mg MK1809 / 25 mg MK1809/ Placebo / Losartan / 25 mg MK1809 with food | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 B-3<br>Part 1; Panel B; Sequence 3: 5 mg MK1809 / Losartan / 100 mg MK1809 / 210 mg MK1809 / Losartan with food | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;|
| Experimental: Part 1 B-4<br>Part 1; Panel B; Sequence 4: Losartan / 25 mg MK1809/ 100 mg MK1809 / Placebo / 25 mg MK1809 with food | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 1 B-5<br>Part 1; Panel B; Sequence 5: Placebo / 25 mg MK1809/ Losartan / 210 mg MK1809 / 25 mg MK1809 with food | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 2 C-1<br>Part 2; Panel C; Sequence 1: 50 mg MK1809 / Placebo / 150 mg MK1809 / 210 mg MK1809 / Losartan | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 2 C-2<br>Part 2; Panel C; Sequence 2: 50 mg MK1809 / 100 mg MK1809/ Placebo / Losartan / 280 mg MK1809 | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 2 C-3<br>Part 2; Panel C; Sequence 3: Losartan / 100 mg MK1809/ 150 mg MK1809 / 210 mg MK1809 / Placebo | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 2 C-4<br>Part 2; Panel C; Sequence 4: 50 mg MK1809 / Losartan / 150 mg MK1809 / Placebo / 280 mg MK1809 | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|
| Experimental: Part 2 C-5<br>Part 2; Panel C; Sequence 5: Placebo / 100 mg MK1809/ Losartan / 210 mg MK1809 / 280 mg MK1809 | Drug: MK1809<br>* single oral doses of MK1809<br>Drug: Comparator: Losartan<br>* single oral doses of 100 mg Losartan<br>* Other names: Losartan;Drug: Comparator: Placebo<br>* Placebo to MK1809<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part I: Area under the plasma concentration (AUC) versus time curve in healthy adult male subjects in the fasted state |  | Through 32 hours postdose | 
| Part 1: Trough plasma concentration in healthy adult male subjects in the fasted state |  | 24 hours postdose | 
| Part 2: Safety and tolerability of rising single oral doses of MK1809 in adult hypertensive patients based on an assessment of clinical and laboratory adverse experiences |  | Duration of study and up to 14 days after administration of the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Area under the plasma concentration (AUC) versus time curve resulting from a single oral dose of MK1809 following a standard high-fat breakfast (compared to that observed with the identical dose level administered in the fasted state) |  | 24 hours postdose | 
| Part 1: Maximum concentration of drug in the plasma (Cmax) resulting from a single oral dose of MK1809 following a standard high-fat breakfast (compared to that observed with the identical dose level administered in the fasted state) |  | Through 32 hours postdose | 
| Part 1: Number of clinical and laboratory adverse experiences (AEs) to assess safety and tolerability |  | Duration of study and up to 14 days after administration of the last dose of study drug | 
| Part 2: Area under the plasma concentration (AUC) versus time curve of the E3174 metabolite |  | Through 32 hours postdose | 
| Part 2: Trough plasma concentration of the E3174 metabolite |  | Through 32 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension