Clinical trial NCT00541385
Conditions: Malaria
Keywords: Falciparum malaria pediatric Coartem artesunate lumefantrine pyronaridine Pyramax
Sponsor: Medicines for Malaria Venture
Start date: 2007-10-01; Completion date: 2008-11-01
Enrollment: 535 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this Phase III clinical study is to demonstrate the efficacy of the fixed combination of pyronaridine artesunate (PA) granule formulation (60:20 mg; pediatric PYRAMAX®) by showing a PCR-corrected adequate clinical and parasitological cure rate (ACPR) of more than 90%.

Secondary objectives of this clinical study are to compare the efficacy (non-inferiority) and safety of the PA granule formulation compared to Coartem® (ie, the combination of artemether/lumefantrine \[AL\]) crushed tablets in a paediatric population and to assess the safety of the PA granule formulation.

Detailed description:
This is a multi-centre, comparative, randomised, open-label, parallel-group study of the efficacy and safety of a 3-day regimen of a fixed combination of PA (3:1) versus AL in the treatment of acute uncomplicated Plasmodium falciparum mono-infection. The study population will include 534 patients, comprising male and female infants and children (body weight ≥5 and \<25 kg) recruited from study sites in East, Central, and West Africa and South East Asia (max. 150 patients/site).

Patients will be randomised in a 2:1 ratio to receive either oral PA (60:20 mg granules) once a day for 3 consecutive days (Days 0, 1, and 2) or AL (20:120 mg crushed tablets) twice a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third Party Investigator unblinded to the study treatment, while the Investigator will remain blinded. For PA, the dose range covered by this regimen is 7.0:2.3 mg to 13.3:4.4 mg, which has been shown to be effective and safe in Phase I and II studies. Posology will be based on body weight ranges for both the PA and AL regimens.

Patients will be confined to the study facility ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs earlier.

The primary efficacy end point for this study is the proportion of subjects with PCR-corrected ACPR on Day 28. Scheduled follow-up visits will continue until completion of the study at 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: Oral pyronaridine/artesunate (PA, 60:20mg granules) once a day for 3 consecutive days (Days 0, 1, and 2).

Posology based on body weight ranges. arm 2: Oral artemether/lumefantrine (AL, 20:120mg crushed tablets) twice a day for 3 consecutive days (Days 0, 1, and 2).

Posology based on body weight ranges.
Interventions: intervention 1: pyronaridine artesunate intervention 2: arthemeter lumefantrine
Intervention descriptions: intervention 1: The strength of the granule formulation is 60:20 mg pyronaridine artesunate per sachet. Depending on their body weight, patients will receive between 1 to 3 pyronaridine artesunate sachets per day, for 3 consecutive days The actual dose-range covered by this regimen is 7.0:2.3 mg/kg to 13.3:4.4 mg/kg pyronaridine artesunate, which has shown to be effective and safe in the phase II studies conducted in children and adults. intervention 2: The strength of the tablet is 20 mg artemether and 120 mg lumefantrine. Depending on their body weight, patients will receive either 1 or 2 crushed tablets twice a day (≥5 to \<15 = 1 tablet, 15 to \<25 kg = 2 tablets), for 3 consecutive days.

Protocol documents: