Open Label Pharmacokinetic Study of OZ439 and Piperaquine on Administration of OZ439+TPGS Granules for Oral Suspension Alone or With Either Piperaquine Phosphate Tablets or Granules for Oral Solution in Healthy Volunteers

Inclusion Criteria

• healthy, male or female, any race aged 18-55 years at screening
• body mass index of 18-30kg/m2 inclusive; and a total body weight >50kg and up to 100kg at screening
• Females must have negative pregnancy test at screening, be non-lactating and of non-childbearing potential confirmed by:
• natural (spontaneous) post-menopausal defined as amenorrheic for 12 months without an alternative medical cause with a screening FSH level >25IU/L for post menopause
• irreversible surgical sterilisation by bilateral oophorectomy or bilateral salpingectomy but not tubal ligation (with or without hysterectomy) at least six months ago
• Must agree to use acceptable methods of contraception Males must use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of treatment or study medication until 3 months following administration of the last dose of study medication

One of the following acceptable methods of contraception must be used:

• Condom & occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository)
• Surgical sterilisation (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
• Female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (as above)
• Female partner uses medically prescribed topically-applied transdermal contraceptive patch and a barrier method (as above)
• Female partner has had documented tubal ligation (sterilization). In addition, a barrier method (as above) must be used
• Female partner has had documented placement of an intrauterine device or system and the use of a barrier method (as above)
• True abstinence: when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Abstinent subjects must agree use one of the above-mentioned contraceptive methods, if sexual relationships start during the study or up to 90 days after the last dose of study drug
• Subjects should not donate egg and sperm from the time of administration of study medication until 3 months after study medication
• Must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures

Exclusion Criteria

• Male subjects with female partner(s) who is (are) pregnant or lactating from the time of the administration of study medication
• Has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion
• History of allergic reaction to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food
• Any 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
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal (excluding appendectomy and cholecystectomy), haematological, endocrinological, immunological, metabolic, neurological, oncological, psychiatric, urological or other disease, or current infection
• History of post-antibiotic colitis
• Electrocardiogram abnormalities in the 12-lead Electrocardiogram (at screening) and/or 24-hour Holter Electrocardiogram (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the ECG analysis
• History of clinically significant Electrocardiogram abnormalities, or any of the following abnormalities at screening or on admission:
• PR >200m