Phase I Study of Pyrimethamine in Healthy Japanese and Caucasian Subjects

This is an interventional treatment trial for Toxoplasmosis focused on measuring Japanese, Caucasian, pharmacokinetics, pyrimethamine, toxoplasmosis Read More

Inclusion Criteria:

• Subjects should be between 20 and 64 years of age inclusive, at the time of signing the informed consent.
• Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• Body weight >= 50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 30.0 kilogram per square meters (kg/m^2) (inclusive).
• Japanese or Caucasian male.
• A male subject must agree to use contraception during the treatment period and until follow-up.
• Japanese ethnic origin defined as having been born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Subjects should also have lived outside Japan for less than 10 years at the time of screening.
• Caucasian subject will be defined as an individual having four grandparents who are all descendants of the original people of Europe.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions of the study.

Exclusion Criteria:

• Alanine aminotransferase (ALT) > 1.5 times upper limit of normal (ULN).
• Bilirubin > 1.5 times ULN (isolated bilirubin > 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 milliseconds (msec).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Abnormal blood pressure as determined by the investigator.
• Hematological values: outside normal range at screening.
• Serum creatinine level: outside normal range at screening visit.
• Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrollment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research.
• Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
• Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
• Positive pre-study drug/alcohol screen.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular use of known drugs of abuse.
• Regular alcohol consumption within 6 months prior to the study defined as: For an average weekly intake of > 14 units for males. One unit is equivalent to 10 grams (g) of alcohol: a can of mid-strength (equivalent to 375 mL) beer, 1 glass (100 mL) of table wine or 1 measure (30 mL) of spirits (including rice wine).
• History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.