title: 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.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  Male 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  Clinical Trial Registry India: CTRI/2009/091/000531.
authors.affiliation: Malariology Department, Institut Pasteur, Abidjan, Côte d'Ivoire. andre_offianan@yahoo.fr.
authors.forename: Offianan Andre
authors.initials: OA
authors.lastname: Toure
authors.affiliation: Department of Clinical Research, School of Medicine, Kigali University Teaching Hospital, University of Rwanda, Butare, Rwanda. s.rulisa@gmail.com.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rulisa
authors.affiliation: National Institute of Malaria Research, New Delhi, India. anvikar@gmail.com.
authors.forename: Anupkumar R
authors.initials: AR
authors.lastname: Anvikar
authors.affiliation: Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India. drbsrao@tatasteel.com.
authors.forename: Ballamudi S
authors.initials: BS
authors.lastname: Rao
authors.affiliation: Department of Paediatrics, Ispat General Hospital, Rourkela, Odisha, India. pitabasmishra@yahoo.co.in.
authors.forename: Pitabas
authors.initials: P
authors.lastname: Mishra
authors.affiliation: Medical Affairs, Clinical Research and Global Head Pharmacovigilance, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India. rajinder.jalali@sunpharma.com.
authors.forename: Rajinder K
authors.initials: RK
authors.lastname: Jalali
authors.affiliation: Corporate Office, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India. sudershanarora@hotmail.com.
authors.forename: Sudershan
authors.initials: S
authors.lastname: Arora
authors.affiliation: CDM and Biostatistics, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India. arjun.roy@sunpharma.com.
authors.forename: Arjun
authors.initials: A
authors.lastname: Roy
authors.affiliation: Medical Global Marketing Corporate Office, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India. nilanjans1962@gmail.com.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Saha
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India. Sunil.Iyer@sunpharma.com.
authors.forename: Sunil S
authors.initials: SS
authors.lastname: Iyer
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd, Gurgaon, Haryana, India. pradeep.sharma@sunpharma.com.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sharma
authors.affiliation: National Institute of Malaria Research, New Delhi, India. neenavalecha@gmail.com.
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
mesh_terms: D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D007560:Cote d'Ivoire; D004338:Drug Combinations; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010545:Peroxides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012432:Rwanda; D013141:Spiro Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013607:Tablets; D010879:Piperazines
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D011804:Quinolines; D013141:Spiro Compounds; D013607:Tablets; C489136:arterolane; C034759:piperaquine; D010879:Piperazines