RBx11160 Phase II Dose Ranging Study RBx/MMV05-06

• Male or female patients aged 13 to 65 years, inclusive.
• Body weight > 30 kg with no clinical evidence of severe malnutrition.
• Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum parasites only. Initial parasite densities appropriate for inclusion will be between 1000 and 100,000 asexual parasites/microL blood.
• Presence of fever (axillary temperature > 37.5 °C or oral or rectal temperature > 38 °C).
• Female patients must be non-lactating and willing to use contraceptive methods during the study period.
• Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If a patient is unable to provide informed consent in writing, a thumbprint to indicate consent in the presence of at least 1 witness is acceptable. If applicable, for adolescents providing written informed consent, assent should be obtained from the patient's legally accepted representative/guardian.
• Willingness and ability to comply with the study protocol for the duration of the study.
• Patient resides within a reasonable distance of the investigational site, so that attendance of all study visits and follow-up by medical staff are logistically feasible.

Exclusion Criteria:

• Patients presenting with a mixed infection (i.e., malaria due to more than 1 causative parasite).
• Patients with severe malaria.
• Any antimalarial treatment during 2 weeks prior to Screening, as assessed by medical history.
• History of hypersensitivity or allergic reactions to artemisinins.
• Patients who have been treated with RBx 11160 in any study.
• Participation in any investigational drug study during the 30 days prior to Screening.
• Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management. These abnormalities include QTc interval > 450 msec at Screening and cardiac conduction disorders, with the exception of right bundle branch block.
• A female patient who is lactating or pregnant at Screening.
• Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhea defined as > 3 episodes of watery stools in the previous 24 hours or patients who have had 3 episodes of vomiting within 24 hours prior to Screening).
• Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at Screening:

Serum creatinine > 1.5 x upper limit of normal (ULN). Aspartate transaminase > 2.5 x ULN. Alanine transaminase > 2.5 x ULN. Alkaline phosphatase > 2.5 x ULN. Total bilirubin > 1.5 x ULN.

• Patients who have had a splenectomy.
• Immunocompromised patients, patients receiving immunosuppressive agents, or patients with known human immunodeficiency virus (HIV) infection. (Screening for these conditions is not required for entry in the study.)
• Evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, psychiatric (e.g., depression, anxiety, psychosis, or schizophrenia) or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
• Patients who have epilepsy or a history of convulsions.