title: Phase I randomized dose-ascending placebo-controlled trials of ferroquine--a candidate anti-malarial drug--in adults with asymptomatic Plasmodium falciparum infection.
abstract: BACKGROUND
  The development and spread of drug resistant Plasmodium falciparum strains is a major concern and novel anti-malarial drugs are, therefore, needed. Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P. falciparum laboratory strains.
  
  
  METHODS
  Adult young male aged 18 to 45 years, asymptomatic carriers of P. falciparum, were included in two-dose escalation, double-blind, randomized, placebo-controlled Phase I trials, a single dose study and a multiple dose study aiming to evaluate oral doses of ferroquine from 400 to 1,600 mg.
  
  
  RESULTS
  Overall, 54/66 patients (40 and 26 treated in the single and multiple dose studies, respectively) experienced at least one adverse event, 15 were under placebo. Adverse events were mainly gastrointestinal symptoms such as abdominal pain (16), diarrhoea (5), nausea (13), and vomiting (9), but also headache (11), and dizziness (5). A few patients had slightly elevated liver parameters (10/66) including two patients under placebo. Moderate changes in QTc and morphological changes in T waves were observed in the course of the study. However, no adverse cardiac effects with clinical relevance were observed.
  
  
  CONCLUSIONS
  These phase I trials showed that clinically, ferroquine was generally well-tolerated up to 1,600 mg as single dose and up to 800 mg as repeated dose in asymptomatic young male with P. falciparum infection. Further clinical development of ferroquine, either alone or in combination with another anti-malarial, is highly warranted and currently underway.
authors.affiliation: Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
authors.forename: Ghyslain
authors.initials: G
authors.lastname: Mombo-Ngoma
authors.forename: Christian
authors.initials: C
authors.lastname: Supan
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Dal-Bianco
authors.forename: Michel A
authors.initials: MA
authors.lastname: Missinou
authors.forename: Pierre-Blaise
authors.initials: PB
authors.lastname: Matsiegui
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Ospina Salazar
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Daniel
authors.initials: D
authors.lastname: Ter-Minassian
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Kombila
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
mesh_terms: D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D058070:Asymptomatic Diseases; D004311:Double-Blind Method; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D000075163:Metallocenes; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010963:Plasmodium falciparum / Q000302:isolation & purification; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D010919:Placebos; C479230:ferroquine