A Study of the Pharmacokinetics and Pharmacodynamics of MK1809

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01033318
First received: December 15, 2009
Last updated: NA
Last verified: December 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: MK1809
Drug: Comparator: Losartan
Drug: Comparator: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Part I: Area under the plasma concentration (AUC) versus time curve in healthy adult male subjects in the fasted state [ Time Frame: Through 32 hours postdose ] [ Designated as safety issue: No ]
  • Part 1: Trough plasma concentration in healthy adult male subjects in the fasted state [ Time Frame: 24 hours postdose ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Duration of study and up to 14 days after administration of the last dose of study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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) [ Time Frame: 24 hours postdose ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Through 32 hours postdose ] [ Designated as safety issue: No ]
  • Part 1: Number of clinical and laboratory adverse experiences (AEs) to assess safety and tolerability [ Time Frame: Duration of study and up to 14 days after administration of the last dose of study drug ] [ Designated as safety issue: Yes ]
  • Part 2: Area under the plasma concentration (AUC) versus time curve of the E3174 metabolite [ Time Frame: Through 32 hours postdose ] [ Designated as safety issue: Yes ]
  • Part 2: Trough plasma concentration of the E3174 metabolite [ Time Frame: Through 32 hours postdose ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: April 2008
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: 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
Other Name: MK1809
Drug: Comparator: Losartan
single oral doses of 100 mg Losartan
Other Name: Losartan
Drug: Comparator: Placebo
Placebo to MK1809

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033318

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Executive Vice President, Clinical and Quantitative Sciences, Merck & Co., Inc.
ClinicalTrials.gov Identifier: NCT01033318     History of Changes
Other Study ID Numbers: 2009_703, MK1809-001
Study First Received: December 15, 2009
Last Updated: December 15, 2009
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Merck Sharp & Dohme Corp.:
Hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Losartan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014