Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials

Malaria Journal

Research

Sarah Arbe-Barnes¹  Robert M Miller¹  Lawrence Fleckenstein²  Isabelle Borghini-Fuhrer³  Stephan Duparc³  Carl J Craft⁴  Chang-Sik Shin⁵ 

[1] Aptiv Solutions, Stevenage BioScience Catalyst, SG1 2FX, Stevenage, UK;College of Pharmacy, University of Iowa (UoI), Iowa City, IA, USA;Medicines for Malaria Venture (MMV), International Center Cointrin, PO Box 1826, Route de Pré-Bois 20, CH-1215, Geneva 15, Switzerland;Medicines for Malaria Venture (MMV), International Center Cointrin, PO Box 1826, Route de Pré-Bois 20, CH-1215, Geneva 15, Switzerland;Libertyville, IL, USA;Shin Poong Pharmaceutical Co Ltd, Seoul, Republic of Korea;

关键词: Pyronaridine-artesunate;    Artemether-lumefantrine;    Mefloquine + artesunate;    Malaria;    Plasmodium falciparum;    Plasmodium vivax;    Randomized clinical trial;   

DOI  :  10.1186/1475-2875-12-70

 received in 2012-11-04, accepted in 2013-02-18,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPyronaridine-artesunate (PA) is indicated for the treatment of acute uncomplicated Plasmodium falciparum and Plasmodium vivax malaria.MethodsIndividual patient data on safety outcomes were integrated from six randomized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum (five studies) or P. vivax (one study) malaria. Efficacy against P. falciparum was evaluated across three Phase III clinical trials.ResultsThe safety population included 2,815 patients randomized to PA, 1,254 to comparators: mefloquine + artesunate (MQ + AS), artemether-lumefantrine (AL), or chloroquine. All treatments were generally well tolerated. Adverse events occurred in 57.2% (1,611/2,815) of patients with PA versus 51.5% (646/1,254) for comparators, most commonly (PA; comparators): headache (10.6%; 9.9%), cough (5.9%; 5.6%) and anaemia (4.5%; 2.9%). Serious averse events were uncommon for all treatments (0–0.7%). Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae. For P. falciparum malaria, day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6% ([1,921/2,052] 95% CI 92.6, 94.7) in the intent-to-treat population and 98.5% ([1,852/1,880] 95% CI 98.0, 99.1) in the per-protocol population. Median parasite clearance time was 24.1 h with PA, 31.9 h with MQ + AS, and 24.0 h with AL. Median fever clearance time was 15.5 h with PA, 15.8 h with MQ + AS, and 14.0 h with AL. By day 42, P. falciparum gametocytes had declined to near zero for all treatments.ConclusionsPyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases. Efficacy was high and met the requirements for use as first-line therapy. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes.Trial registrationClinicaltrials.gov: NCT00331136; NCT00403260; NCT00422084; NCT00440999; NCT00541385; NCT01594931

【 授权许可】

CC BY   
© Duparc et al.; licensee BioMed Central Ltd. 2013