Pyronaridine Artesunate 3:1 Granule Formulation vs. Coartem© Crushed Tablets in P. Falciparum Malaria Pediatric Patients
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.
Timeline
- Start
- 2007-10
- Primary completion
- 2008-09
- Completion
- 2008-11
Outcome
Met primary endpoint
paper The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P < .0001). PMID 23113947 ↗
paper Pyronaridine-artesunate was non-inferior to artemether-lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). PMID 23113947 ↗
Publications
- Results Kayentao K, Doumbo OK, Penali LK, Offianan AT, Bhatt KM, Kimani J, Tshefu AK, Kokolomami JH, Ramharter M, de Salazar PM, Tiono AB, Ouedraogo A, Bustos MD, Quicho F, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial. Malar J. 2012 Oct 31;11:364. doi: 10.1186/1475-2875-11-364.
- Ramharter M, Djimde AA, Borghini-Fuhrer I, Miller R, Shin J, Aspinall A, Richardson N, Wibberg M, Fleckenstein L, Arbe-Barnes S, Duparc S. Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study. Malar J. 2024 Feb 28;23(1):61. doi: 10.1186/s12936-024-04885-3.
- Ayyoub A, Methaneethorn J, Ramharter M, Djimde AA, Tekete M, Duparc S, Borghini-Fuhrer I, Shin JS, Fleckenstein L. Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1450-8. doi: 10.1128/AAC.02004-15.
- Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J. 2013 Feb 21;12:70. doi: 10.1186/1475-2875-12-70.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Artemether | Small molecule | 20 mg | Oral |
| Comparator | Artemether | Small molecule | 40 mg | Oral |
| Subject | Artesunate | Small molecule | 2.3 mg/kg | Oral |
| Subject | Artesunate | Small molecule | 4.4 mg/kg | Oral |
| Subject | Pyronaridine | Unknown | 7 mg/kg | Oral |
| Subject | Pyronaridine | Unknown | 13.3 mg/kg | Oral |
| Comparator | lumefantrine | Small molecule | 120 mg | Oral |
| Comparator | lumefantrine | Small molecule | 240 mg | Oral |