Safety, Tolerability and Antimalarial Activity of Single Doses of OZ439 and PQP

Inclusion Criteria

• Adult (male and female) subjects between 18 and 55 years of age inclusive, who do not live alone (from inoculation day until at least the end of the Riamet® treatment) and will be contactable and available for the duration of the trial and contactable up to 2 weeks following the End of Study visit (approximately 8.5 weeks).
• Body weight minimum 50 kg, body mass index between 18 and 32 kg/m2, inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history, complete physical examination and special investigations).
• Vital signs after 5 minutes resting in supine position:
• 90 mmHg ≤ systolic blood pressure (SBP) ≤ 140 mmHg,
• 40 mmHg ≤ diastolic blood pressure (DBP) ≤ 90 mmHg,
• 40 bpm ≤ heart rate (HR) ≤ 100 bpm.
• Must have QTcF ≤450 ms, QTcB ≤450 ms for male subjects, QTcF ≤470 ms, QTcB ≤470 ms for female subjects and PR interval ≤210 ms at screening and at pre-inoculation on inoculation day.
• Heterosexual women of childbearing potential should be surgically sterile or using an insertable, injectable, transdermal or combination oral contraceptive approved by the TGA combined with a barrier contraceptive for the duration of the study, and have negative results on a urine pregnancy test done before inoculation. Abstinent, heterosexual female subjects must agree to start a double method if they start a sexual relationship during the study. Adequate contraception does not apply to subjects of childbearing potential with same sex partners (abstinence from penile-vaginal intercourse), when this is their preferred and usual lifestyle. Female subjects with same sex partners must not be planning in vitro fertilisation within the required contraception period.

Women of non-childbearing potential who will not require contraception during the study are defined as: post-menopausal (spontaneous amenorrhoea for ≥ 12 months, or spontaneous amenorrhoea for 6-12 months and follicle-stimulating hormone (FSH) ≥ 40 IU/mL; either should be together with the absence of oral contraceptive use for > 12 months).

Male subjects participating must agree to use a double-barrier method of contraception including condom plus diaphragm or condom plus intrauterine device or condom plus stable oral/transdermal/injectable hormonal contraceptive by the female partner from the time of informed consent through to 90 days after the last dose of OZ439 and PQP. Abstinent male subjects must agree to start a double-barrier method if they begin sexual relationships during the study and up to 90 days after the last dose of study drug.

Male subjects with female partners that are surgically sterile, or male subjects who have undergone sterilisation and have had testing to confirm the success of the sterilisation may also be included.

• Having given written informed consent prior to undertaking any study-related procedure.
• Must be willing and able to communicate and participate in the whole study. -

Exclusion Criteria

• Haematology, clinical chemistry, coagulation or urinalysis results at screening or on admission prior to Inoculation or IMP administration that are outside of Sponsor-approved clinically acceptable laboratory ranges documented in the laboratory manual or are considered clinically relevant.
• Any history of malaria or participation in a previous malaria challenge study.
• Must not have travelled to or lived (>2 weeks) in a malaria-endemic region during the past 12 months or planned travel to a malaria-endemic region during the course of the study (for endemic regions see https://map.ox.ac.uk/country-profiles/#!/). Bali is not considered a malaria-endemic region.
• Participation in any investigational product study within the 12 weeks preceding IMP administration.
• Has evidence of increased cardiovascular disease risk (defined as >10%, 5-year risk for those greater than 35 years of age, as determined by the Australian Absolute Cardiovascular Disease Risk Calculator (http://www.