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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: MK1809; Drug: Comparator: Losartan; Drug: Comparator: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

15

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2007
• Primary Completion (Actual): June 19, 2008
• Study Completion (Actual): June 19, 2008

Study Registration Dates

• First Submitted: December 15, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimate): December 16, 2009

Study Record Updates

• Last Update Posted (Actual): September 26, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 1809-001; MK1809-001; 2009_703