Safety, Tolerability and Pharmacokinetic Profile of Ascending Oral Doses of MMV390048, Part A

Inclusion Criteria

• Completion of the written informed consent process.
• Men or WNCBP age 18 to 55 years, in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Male subjects agree to use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of study medication until 130 (90+40) days following administration of the investigational medicinal product. One of the following acceptable methods of contraception must be utilized:
• Condom and occlusive cap (diaphragm or cervical/vault caps)
• Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
• The subject's female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
• The subject's female partner uses medically prescribed topically-applied transdermal contraceptive patch and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
• The subject's female partner has undergone documented tubal ligation (female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
• The subject's female partner has undergone documented placement of an intrauterine device or intrauterine system. In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
• True abstinence: when this is 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 have to agree to use 1 of the above-mentioned contraceptive methods, if they start sexual relationships during the study and for up to 100 days after the last dose of study drug.
• Women subjects must be of non-childbearing potential (WNCBP) as per one of the following definitions:
• Natural (spontaneous) post-menopausal defined as being amenorrhoeic for at least 12 months without an alternative medical cause with a screening follicle stimulating hormone level consistent with local laboratory levels for post-menopause.
• Premenopausal with irreversible surgical sterilization by hysterectomy and/or bilateral oophorectomy or salpingectomy at least 6 months before screening (as determined by subject medical history).
• Haematology, clinical chemistry and urinalysis results at screening that are within the local laboratory reference range or, if outside the range, not clinically significant as judged by the Investigator. More specifically, serum creatinine, hepatic transaminase enzymes (AST ALT), and total bilirubin (unless the subject has documented Gilbert syndrome) should not exceed the upper laboratory norm and haemoglobin must be equal to or higher than the lower limit of the normal range.
• Total body weight greater than 50 kg and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive).
• Non-smoker or ex-smoker for more than 90 days prior to screening, or smoke no more than 5 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Agree to stay in contact with the study site for the duration of the study and up to 2 weeks following the end of study visit, provide updated contact information as necessary, and have no current plans to move away from the study area for the duration of the study.

Exclusion Criteria

• Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of the administration of study medication.
• Women of childbearing potential, def