auranofin pk following oral dose administration

Conditions: Amoebiasis

Summary: phase i, open-label study in 15 healthy adult subjects receive 6 mg of auranofin orally once every 24 hours for 7days. blood samples will be taken for 17 weeks following the last dose of auranofin for determination of terminal phase pharmacokinetic parameters. stool samples will also be obtained for the measurement of gold.

auranofin is a gold-containing chemical salt, granted as an orphan drug status for use in the treatment of amebiasis. amebiasis is a parasitic infection caused by the protozoon entamoeba histolytica. it affects about ten percent of the world's population, being especially common in areas with poor health infrastructure. this is a phase i open label, multiple dose study to evaluate the pharmacokinetics of auranofin following oral dose administration for 7 days to healthy subjects. 15 healthy male and female volunteers age 18-45 years, inclusive enrolled in one site. the study duration is 48 weeks and up to 23 weeks of subject participation. the primary objective characterizes the pharmacokinetics of gold, given as auranofin, during and after 7 days of once daily oral dose administration. the secondary objective monitor the safety of auranofin during and after 7 days of oral administration.

Eligibility criteria:
inclusion criteria: -personally signed and dated informed consent document. -healthy male or female of non-childbearing potential, between the ages of 18 and 45 years, inclusive. healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, complete physical examination including vital signs, and clinical laboratory tests. non-childbearing potential is defined as amenorrheic for at least 2 years plus a serum follicle-stimulating hormone (fsh) level \> 30 iu/l, or documented bilateral oophorectomy and/or hysterectomy, or tubal ligation. -body mass index (bmi) of 18 to 30 \[weight (kg)\]/ \[height (m)\^2\] inclusive; and a total body weight \> 50 kg (110 lbs) and \< 122 kg (250 lbs) at the screening visit. -male subjects willing to use appropriate contraception for the duration of the study. -willing and able to comply with scheduled visits, dosing plan, laboratory tests, and other study procedures. exclusion criteria: -evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, musculoskeletal, immunologic, neurologic or dermatologic disease (including drug allergies that are clinically significant) which in the opinion of the investigator could impact the participation of the subject in the study or the assessment of the study endpoints. -current evidence of or history of malignancy (excepting completely treated cervical cancer in situ or intraductal carcinoma of the breast, or \ /= 1 pint (473 ml) within 30 days prior to study drug administration. -plasma and platelet donation within 14 days prior to study drug administration. -screening liver function tests (alanine aminotransferase \[alt\] or aspartate aminotransferase \[ast\]) greater than upper limit of normal (uln). -evidence of hepatitis b, hepatitis c or human immunodeficiency virus (hiv) infection upon serological testing at the screening visit. -evidence of active infection or febrile illness (e.g., bronchopulmonary, urinary or gastrointestinal) within 7 days prior to study drug administration. -history of allergy to auranofin or any of the excipients in the capsules. (excipients per the package insert of auranofin are listed in section 6.1) -any other condition that, in the opinion of the investigator, poses a risk to the safety of the individual or the valid conduct of the study.

Keywords: amebiasis auranofin pharmacodynamics pharmokinetics