A Dose-escalation Study to Investigate Safety and Toleration of OZ439

Inclusions:

• healthy males or females of any race aged 18 - 55 years
• BMI of 18 - 30 kg/m2 inclusive at screening
• Agree to use acceptable methods of contraception if of childbearing potential
• Capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form
• Females are either of child bearing potential or are confirmed as post-menopausal. Post-menopausal is defined as being amenorrheic for 12 months without an alternative medical cause with a screening FSH level ≥ 25.8 IU/L

Exclusions:

• Male subjects with female partner(s) who is (are) pregnant or lactating from the time of the first administration of study medication
• Clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion
• History of allergic reactions to artemisinin-based compounds or any other clinically relevant allergy to drugs or food
• Clinically relevant history of both soya and cow's milk intolerance/allergy
• Clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission
• Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) and/or 24-hour 5 lead Holter ECG (at screening)
• Any abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes
• Prolonged QTcF >450 ms or shortened QTcF <340 ms, or family history of Long QT Syndrome
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological, psychiatric, or other disease
• Positive results in any of the serology tests for Hepatitis B Surface Antigen (HbsAg), anti Hepatitis core antibody (anti HBc Ig G [and anti HBc IgM if IgG is positive], Hepatitis C antibodies (anti HCV), and HIV 1 and 2 antibodies (anti HIV 1/2)
• Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates, and methadone) or from the alcohol breath test at screening and on admission
• History or clinical evidence of alcohol or drug abuse. Alcohol abuse is defined as regular weekly intake of more than 21 units for males and 14 units for females; drug abuse is defined as compulsive, repetitive and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms
• Is pregnant or lactating (female subjects who are of childbearing potential must have negative pregnancy tests at screening and admission)
• Mentally handicapped
• Participation in a drug trial within 90 days prior to first drug administration
• Use of any medication (incl. over-the-counter (OTC) medication) within 2 weeks prior to drug administration (Day 1) or within less than 10 times the elimination half-life of the respective drug, or anticipated concomitant medication during the treatment periods, (whichever is longer), including herbal, traditional and alternative medications. Excluding oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants. Limited amounts (4g/day for 2 days) of paracetamol will be permitted for the treatment of AEs
• Treatment with herbal supplements during the 7 days prior to drug administration, or use of vitamins during 48 hours prior to drug administration
• Is not permitted to use strong inhibitors and/or inducers of CYP450 within 21 days prior to the planned first drug administration
• Subjects have veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins that are difficult to locate, access or puncture veins with a tendency to rupture during or after puncture)
• Blood ALT, AST and bilirubin should be in the