title: A Phase 3, Double-Blind, Randomized Study of Arterolane Maleate-Piperaquine Phosphate vs Artemether-Lumefantrine for Falciparum Malaria in Adolescent and Adult Patients in Asia and Africa.
abstract: BACKGROUND
  Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria.
  
  
  METHODS
  In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42.
  
  
  RESULTS
  Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable.
  
  
  CONCLUSIONS
  AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance.
  
  
  BACKGROUND
  India. CTRI/2009/091/000101.
authors.affiliation: Malariology Department, Institut Pasteur Côte d'Ivoire, Abidjan.
authors.forename: Offianan Andre
authors.initials: OA
authors.lastname: Toure
authors.affiliation: Epidemiology and Clinical Research Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
authors.affiliation: Centre de recherches cliniques et epidemiologiques de Mont Amba, Centre hospitalier de Mont Amba, Ecole de Sante Publique, Universite de Kinshasa, Democratic Republic of Congo.
authors.forename: Antoinette K
authors.initials: AK
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authors.affiliation: Chókwè Health Research and Training Centre, Mozambique.
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authors.affiliation: Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand.
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authors.affiliation: Department of Parasitology Guediawaye District Hospital, University Cheikh Anta Diop, Dakar Fann, Senegal.
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authors.affiliation: Department of Medicine, Government Wenlock District Hospital, Mangalore, Karnataka, India.
authors.forename: Bappanaidu Hoigegudde Krishnamurthy
authors.initials: BHK
authors.lastname: Rao
authors.affiliation: Malaria Research and Training Center, University of Science, Techniques and Technologies Bamako, Mali.
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authors.lastname: Mohanty
authors.affiliation: Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India.
authors.forename: Ballamudi Srinivas
authors.initials: BS
authors.lastname: Rao
authors.affiliation: Epidemiology and Clinical Research Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Anupkumar R
authors.initials: AR
authors.lastname: Anvikar
authors.affiliation: College of Medicine, Blantyre, Malawi.
authors.forename: Victor
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authors.affiliation: Malaria Research Initiative Bandarban, Sadar District Hospital, Bangladesh.|Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria.
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authors.affiliation: CDM & Biostatistics, Medical Affairs & Clinical Research.
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authors.affiliation: Clinical Pharmacology & Pharmacokinetics.
authors.forename: Sunil S
authors.initials: SS
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authors.affiliation: Clinical Pharmacology & Pharmacokinetics.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Medical Global Marketing, Corporate Office.
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authors.affiliation: Medical Affairs & Clinical Research, Sun Pharmaceutical Industries Limited (erstwhile Ranbaxy Laboratories Ltd), Gurgaon, Haryana, India.
authors.forename: Rajinder K
authors.initials: RK
authors.lastname: Jalali
authors.forename: Landry
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authors.lastname: Tiacoh
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authors.forename: Noppadon
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authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Ndiaye
authors.forename: Deepak
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authors.forename: Ntamabyaliro Nsengi
authors.initials: NN
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mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa / Q000453:epidemiology; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000627:therapeutic use; D001208:Asia / Q000453:epidemiology; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000627:therapeutic use; D006207:Half-Life; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007194:India / Q000453:epidemiology; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010545:Peroxides / Q000008:administration & dosage* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000008:administration & dosage* / Q000627:therapeutic use; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000077549:Artemether; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D006573:Heterocyclic Compounds, 1-Ring; D000078102:Lumefantrine; D010545:Peroxides; D011804:Quinolines; D013141:Spiro Compounds; C489136:arterolane; C034759:piperaquine; D010879:Piperazines
keywords: artemisinin combination therapy; arterolane maleate; fixed-dose combination; malaria; once-daily dose