A Study of the Pharmacokinetics and Pharmacodynamics of MK1809

• 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 ]

• 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 ]

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.

• 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-1

  Part 1; Panel A; Sequence 1:

  2 mg MK1809 / placebo / 50 mg MK1809 / 150 mg MK1809 / 100 mg Losartan

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 A-2

  Part 1; Panel A; Sequence 2:

  Losartan / 10 mg MK1809 / placebo / 150 mg MK1809 / 280 mg MK1809

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 A-3
  Part 1; Panel A; Sequence 3 2 mg MK1809 / 10 mg MK1809 / Losartan / Placebo / 280 mg MK1809
  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 A-4
  Part 1; Panel A; Sequence 4 2 mg MK1809 / Losartan / 50 mg MK1809 / 150 mg MK1809 / Placebo
  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 A-5

  Part 1; Panel A; Sequence 5:

  Placebo / 10 mg MK1809 / 50 mg MK1809 / Losartan / 280 mg MK1809

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 B-1

  Part 1; Panel B; Sequence 1:

  5 mg MK1809 / Placebo / 100 mg MK1809 / 210 mg MK1809 / Placebo with food

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Placebo
• Experimental: Part 1 B-2

  Part 1; Panel B; Sequence 2:

  5 mg MK1809 / 25 mg MK1809/ Placebo / Losartan / 25 mg MK1809 with food

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 B-3

  Part 1; Panel B; Sequence 3:

  5 mg MK1809 / Losartan / 100 mg MK1809 / 210 mg MK1809 / Losartan with food

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: 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

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 1 B-5

  Part 1; Panel B; Sequence 5:

  Placebo / 25 mg MK1809/ Losartan / 210 mg MK1809 / 25 mg MK1809 with food

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 2 C-1

  Part 2; Panel C; Sequence 1:

  50 mg MK1809 / Placebo / 150 mg MK1809 / 210 mg MK1809 / Losartan

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 2 C-2

  Part 2; Panel C; Sequence 2:

  50 mg MK1809 / 100 mg MK1809/ Placebo / Losartan / 280 mg MK1809

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 2 C-3

  Part 2; Panel C; Sequence 3:

  Losartan / 100 mg MK1809/ 150 mg MK1809 / 210 mg MK1809 / Placebo

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 2 C-4

  Part 2; Panel C; Sequence 4:

  50 mg MK1809 / Losartan / 150 mg MK1809 / Placebo / 280 mg MK1809

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo
• Experimental: Part 2 C-5

  Part 2; Panel C; Sequence 5:

  Placebo / 100 mg MK1809/ Losartan / 210 mg MK1809 / 280 mg MK1809

  Interventions:

  • Drug: MK1809
  • Drug: Comparator: Losartan
  • Drug: Comparator: Placebo

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