Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated P. Falciparum Malaria In Children In Africa

Phase 2/3, Open-Label, Comparative Trial Of Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In Children In Africa

The primary objective is to confirm the hypothesis that azithromycin used in combination with chloroquine is non-inferior to artemether- Lumefantrine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum in children in African countries.

Inclusion Criteria:

• Girls and boys ≥5 years to ≤12 years (Cohort 1); and ≥6 to ≤59 months of age (Cohort 2) with uncomplicated, symptomatic malaria as indicated by the presence of the following:
• Blood smears positive for monoinfection with P. falciparum and asexual parasitemia between 1000 -100,000 parasites/µL;
• Documented fever (38.0°C/100.4°F rectal or tympanic; 37.2°C/99.0°F axillary or 37.5°C/99.5°F oral) or history of fever (as reported by the legally acceptable representative) within the prior 24 hours;
• Appropriate for outpatient treatment;
• Blood glucose ≥60 mg/dL;
• Hemoglobin ≥6 g/dl or hematocrit ≥18% without signs of anemia-induced Congestive Heart Failure (CHF);
• Negative urine pregnancy test for females ≥10 years of age (and of child bearing potential)

Exclusion Criteria:

• Peripheral blood smear positive for mixed infection with multiple Plasmodium spp.
• Severe or complicated malaria including subjects with any of the following:
• Impaired consciousness (eg, obtundation, unarousable coma), seizures or abnormal neurologic exam suggestive of severe or complicated malaria;
• Known hemoglobinuria;
• Jaundice;
• Respiratory distress;
• Persistent vomiting;
• Gross hematuria, as reported by the subject's legally acceptable representative;
• Recent history of convulsions;
• Inability to drink or breastfeed;
• Unable to sit or stand as appropriate for age;
• Known pregnancy or breast-feeding or positive urine pregnancy test (females ≥10 years of age and of child bearing potential);
• History of allergy to or hypersensitivity to azithromycin, any macrolide, chloroquine, artemether, any artemisinin derivative, lumefantrine;
• Any contraindication to any study drug including AZ, CQ and AL;
• History of treatment with any antimalarial drug (such as halofantrine, chloroquine, quinine, mefloquine, Malarone, SP, artemisinin compounds) or antibacterial with known antimalarial activity (macrolides, doxycycline, clindamycin) within 2 weeks prior to enrollment of a subject (and/or of the mother of a subject who is being breastfed) into the study;
• Known or suspected cardiovascular, hepatic or renal abnormality that in the opinion of the investigator would place the subject at increased risk to participate in the study.