Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study

Malaria Journal

Research

Arjun Roy¹  Pradeep Sharma²  Sunil S. Iyer²  Sudershan Arora³  Stephen Rulisa⁴  Ballamudi S. Rao⁵  Pitabas Mishra⁶  Offianan Andre Toure⁷  Rajinder K. Jalali⁸  Nilanjan Saha⁹  Neena Valecha^1,10  Anupkumar R. Anvikar^1,10 

[1] CDM and Biostatistics, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India;Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India;Corporate Office, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India;Department of Clinical Research, School of Medicine, Kigali University Teaching Hospital, University of Rwanda, Butare, Rwanda;Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India;Department of Paediatrics, Ispat General Hospital, Rourkela, Odisha, India;Malariology Department, Institut Pasteur, Abidjan, Côte d’Ivoire;Medical Affairs, Clinical Research and Global Head Pharmacovigilance, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India;Medical Global Marketing Corporate Office, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India;National Institute of Malaria Research, New Delhi, India;

关键词: Artemisinin combination therapy;    Arterolane maleate;    Piperaquine phosphate;    Malaria;    Paediatric;    PCT;    FCT;    PCR-corrected ACPR;    Fixed dose combination;   

DOI  :  10.1186/s12936-015-0982-y

 received in 2015-02-14, accepted in 2015-11-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years.MethodsMale and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph.ResultsA total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11–100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0–24.0) and 10 h (95 % CI 4.0–18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study.ConclusionThe findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and safety results observed in children warrants further studies on FDC of arterolane maleate and PQP dispersible tablets.Trial Registration: Clinical Trial Registry India: CTRI/2009/091/000531

【 授权许可】

CC BY   
© Toure et al. 2015