Conditions: Plasmodium Falciparum Malaria
Keywords: malaria antimalarial artemisinin based combination therapy (ACT) pyronaridine artesunate (Pyramax)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 477
Healthy volunteers: no

Brief summary:
The primary trial objective is to determine the clinically effective dose of orally administered pyronaridine/artesunate (Pyramax®, PA) with a 3:1 ratio to treat adults with acute, symptomatic, uncomplicated P. falciparum malaria in South East Asia and Africa. Secondary trial objectives are to determine the safety of once-daily dosing for 3 days of PA and to explore possible ethnic differences in safety or efficacy.

Detailed description:
This is a double-blind, multicentre, randomized, parallel group, dose-finding study of the efficacy, safety and tolerability of a once-daily 3-day regimen of PA with a 3:1 weight/weight ratio for patients with acute, symptomatic, uncomplicated P. falciparum malaria. Patients will be recruited from 5 to 7 study sites in endemic regions of South East Asia and Africa and will be randomized to 1 of 3 treatment groups differing in dosage, with 160 patients per group (n-480). Randomization will be balanced within each study site across all 3 study groups in pre-assigned treatment blocks.

The first dose will be administered on Day 0 and patients will remain hospitalized for at least 4 days whilst undertaking the 3-day regimen. Patients will remain near the study site for a minimum of 7 days or once fever and parasite clearance is confirmed (assessed by 3 negative readings of fever and/or slide).

The primary efficacy end point is the cure rate on Day 28 - the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR). Despite this Day 28 end point, the relatively long half-life of pyronaridine necessitates follow-up until Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.

Arms:
arm 1: pyronaridine tetraphosphate 6 mg/kg and artesunate 2 mg/kg arm 2: pyronaridine tetraphosphate 9 mg/kg and artesunate 3 mg/kg arm 3: pyronaridine tetraphsophate 12 mg/kg and artesunate 4 mg/kg

Interventions: intervention 1: pyronaridine/artesunate
Intervention descriptions: intervention 1: Tablets of fixed dose combination of pyronaridine and artesunate at a ratio of 3:1. The tablets were taken daily for 3 days.

Protocol document: