A Comparison of the Bioavailability of OZ439 When Delivered Directly to the Small Intestine, or Via the Oral Route

Inclusion Criteria

• Healthy males, or females of non-childbearing potential ie surgically sterilised or post-menopausal
• Age 18 to 55 years
• Body mass index of 18 to 30 kg/m2 inclusive
• Total body weight >50 kg
• Healthy as determined by pre-study medical history, physical examination (including body temperature) and 12-lead ECG
• Must have haematology, clinical chemistry and urinalysis results at screening that are within the reference range or ncs
• Must agree to use an adequate method of contraception
• Must demonstrate their ability to swallow an empty size 000 capsule
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent

Exclusion Criteria

• Evidence or history of clinically significant oncological, pulmonary, chronic respiratory, hepatic, cardiovascular, haematological, metabolic, neurological, immunological, nephrological, endocrine or psychiatric disease, or current infection
• Clinically relevant abnormalities in the ECG (12 standard leads) and/or QTcF >450 ms (males) or >470 ms (females)
• Evidence or history of clinically significant GI disease or surgery (excluding appendectomy or cholecystectomy)
• Any condition that could possibly affect drug absorption, eg gastrectomy or diarrhoea
• History of post-antibiotic colitis
• History of any drug or alcohol abuse in the past 2 years prior to screening
• Subjects who have a breath carbon monoxide reading of greater than 10 ppm at screening. Subjects who are tobacco users (including smokers and users of snuff, chewing tobacco and other nicotine or nicotine-containing products) must have stopped use within 90 days before screening
• Receipt of an investigational drug or participation in another clinical research study within the previous 3 months
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee
• Subjects who have previously been enrolled in this study
• Use of any prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements within 14 days prior to the first dose
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab)or human immunodeficiency virus (HIV-1 or HIV-2 antibody) results
• Positive urine drug screen result
• History of intolerance or hypersensitivity to artemisinins
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
• Presence or history of allergy requiring treatment; hayfever is allowed unless it is active
• Donation or loss of >400 mL of blood within the previous 3 months
• Haemoglobin result below the lower limit of the reference range
• Regular alcohol consumption in males >21 units per week and females >14 units per week
• Subjects who do not have suitable veins
• Acute diarrhoea or constipation in the 7 days before the predicted first study day.
• Presence of non-removable metal objects in the abdomen
• Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years
• Failure to satisfy the investigator of fitness to participate for any other reason