- Healthy Japanese men age 20-45.
- BMI within 17.6 to 26.4 kg/m2 and body weight greater than or equal to 45 kg.
- Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Must
be able to abstain from smoking within 48 hours before study day 1 until the end of
the inpatient confinement period.
- Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal,
endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.
- Any surgical or medical condition that may interfere with the absorption,
distribution, metabolism, or excretion of the test article (e.g., resection of liver,
kidney, gallbladder, or gastrointestinal tract).
- Acute disease state.
- Any history of clinically important cardiac arrhythmias. Family history of long QT
syndrome, Torsades de Pointes or unexpected cardiac death.
- Any clinically important deviation from normal limits in physical examination, vital
signs, 12-lead electrocardiograms (ECGs), or clinical laboratory test results.
Creatinine levels must be less than or equal to the upper limit of normal at
screening.
- Demonstration of a positive orthostatic test at screening. The definition of a
positive test is a greater than or equal to 20 mm Hg decrease in systolic blood
pressure, greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or a
greater than or equal to 30 bpm increase in pulse rate, after standing for 3 minutes.
- Positive serologic findings for human immunodeficiency virus (HIV) antigen and
antibodies, hepatitis B surface antigen (HbsAg), and/or hepatitis C virus (HCV)
antibodies.
- Positive findings of urine drug screen.
- History of any clinically important drug allergy or adverse drug reaction (e.g.,
relapsing dermatitis, drug hypersensitivity, drug allergy, hypersensitivity to
ingredient in the test articles or angioedemas)
- Use of any investigational drug within 90 days before study day 1 or prescription drug
within 30 days before study day 1.
- Consumption of any caffeine-containing products.
- Consumption of grapefruit or grapefruit-containing products within 72 hours before
study day 1 until the end of the inpatient confinement period.
- Use of any over-the-counter drugs, including herbal supplements (except for the
occasional use of vitamins less than or equal to 100% of the recommended daily
allowance), within 14 days before study day 1.