title: Safety, efficacy and pharmacokinetic evaluations of a new coated chloroquine tablet in a single-arm open-label non-comparative trial in Brazil: a step towards a user-friendly malaria vivax treatment.
abstract: BACKGROUND
  Malaria remains a major public health problem, with half the world population at risk of contracting malaria. The effects of Plasmodium vivax on prosperity and longevity have been highlighted in several recent clinical case reports. The first line of vivax treatment drugs has seen no radical innovation for more than 60 years. This study introduces a subtle incremental innovation to vivax treatment: a chloroquine and primaquine co-blister. The co-blister includes a new chloroquine formulation incorporating coated tablets to mask the drug's bitter taste and user-friendly packaging containing tablets of each drug, which may improve patient adherence and facilitate the appropriate use of the drugs. This new formulation will replace the non-coated chloroquine distributed in Brazil.
  
  
  METHODS
  Patients were orally treated with 150 mg coated chloroquine tablets for 3 days: an initial 450 mg dose, followed by two 300 mg doses. The patients were treated concomitantly with two 15 mg primaquine tablets for 7-9 days, according to their weight. The primary objective of this study was to prove parasitological and clinical cure rates above 90 % by day 28.
  
  
  RESULTS
  This single-arm open-label non-comparative trial was conducted according to the WHO recommended methodology for the surveillance of anti-malarial drug efficacy in the Brazilian Amazon. On day 28, the parasitological and clinical response was adequate in 98.8 % of patients (CI 95 % 93.4-100 %). The success rate on day 3 was 100 %, and the cumulative success rate by day 28 was 98.8 % (CI 95 % 91.7-99.8 %). There were no serious adverse events, with most adverse events classified as mild. The pharmacokinetic parameters of chloroquine analysed in whole blood dry spot samples showed mean (coefficient of variation) Cmax and AUC0-t values of 374.44 (0.35) and 3700.43 (0.36) ng/mL, respectively.
  
  
  CONCLUSIONS
  This study reports an appropriate safety and efficacy profile of a new formulation of coated chloroquine tablets for vivax malaria treatment in the Brazilian Amazon. The cure rates meet the WHO efficacy criteria, supporting current Brazilian guidelines and the use of the formulation for vivax malaria treatment. Nevertheless, further studies should be conducted to address adherence and the effectiveness of the formulation. Trial registration RBR-77q7t3-UTN: U1111-1121-2982. Registered 10th May 2011.
authors.affiliation: Tropical Medicine Research Center of Rondônia (CEPEM), Porto Velho, Rondônia, Brazil.|Laboratory of Parasitology, National Institute of Infectious Disease, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.|Federal University of Rondônia (UNIR), Porto Velho, Rondônia, Brazil.
authors.forename: Dhelio
authors.initials: D
authors.lastname: Pereira
authors.affiliation: Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. andredaher@gmail.com.|Vice-presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. andredaher@gmail.com.|Liverpool School of Tropical Medicine, Liverpool, UK. andredaher@gmail.com.
authors.forename: André
authors.initials: A
authors.lastname: Daher
authors.affiliation: Laboratory of Parasitology, National Institute of Infectious Disease, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Graziela
authors.initials: G
authors.lastname: Zanini
authors.affiliation: Vice-presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Ivan
authors.initials: I
authors.lastname: Maia
authors.affiliation: Laboratory of Pharmacokinetics (Sefar), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Lais
authors.initials: L
authors.lastname: Fonseca
authors.affiliation: Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Pitta
authors.affiliation: Tropical Medicine Research Center of Rondônia (CEPEM), Porto Velho, Rondônia, Brazil.
authors.forename: Rosilene
authors.initials: R
authors.lastname: Ruffato
authors.affiliation: National Programme of Malaria Control, Ministry of Health, Brasília, Brazil.
authors.forename: Paola
authors.initials: P
authors.lastname: Marchesini
authors.affiliation: Julio Müller Hospital, Federal University of Mato Grosso, Cuiabá, Brazil.
authors.forename: Cor Jesus
authors.initials: CJ
authors.lastname: Fontes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001938:Brazil; D002738:Chloroquine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011319:Primaquine / Q000008:administration & dosage; D013607:Tablets / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D013607:Tablets; D002738:Chloroquine; D011319:Primaquine
keywords: Adherence; Antimalarial treatment; Chloroquine; Clinical trial; Malaria; Pharmacokinetics; Plasmodium vivax