Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria (FARM)

This study has been terminated.
(Company decision to modify the ferroquine development strategy; discontinuation not due to safety or activity unexpected findings)
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00988507
First received: October 1, 2009
Last updated: June 27, 2011
Last verified: June 2011

October 1, 2009
June 27, 2011
October 2009
November 2010   (final data collection date for primary outcome measure)
Recrudescent infections at D28 in the groups with ferroquine associated with artesunate. Recrudescence is defined as the recurrence of the same original strain of Plasmodium falciparum regardless of clinical symptoms [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00988507 on ClinicalTrials.gov Archive Site
  • Cure rate at Day 28 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Parasite Clearance Time (Median). [ Time Frame: up to 63 days ] [ Designated as safety issue: No ]
  • Fever Clearance Time (Median) [ Time Frame: up to 63 days ] [ Designated as safety issue: No ]
  • Recrudescent infections at Day 28 in the ferroquine group in monotherapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Recrudescent infections at Day 63 [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Adequate Clinical and Parasitological Response (ACPR) at D28 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Parallel Group, Double-blind, Randomized Study Assessing the Efficacy, Safety and Pharmacokinetic Profiles of Ferroquine Associated With Artesunate and a Single-blind Dose Level of Ferroquine Alone in a 3-day Treatment of Uncomplicated Malaria Due to Plasmodium Falciparum in an Immune Symptomatic African Adult and Pediatric Population.

Primary objective: To assess the Day 28 efficacy defined as the percentage of patients with no parasitic recrudescence, of 3 treatment groups - 3 dose levels of ferroquine associated with artesunate - for a 3-day treatment.

Secondary objectives:

  • To assess the efficacy of ferroquine at one dose level alone for a 3-day treatment.
  • To assess the clinical safety of 4 treatment groups - 3 dose levels of ferroquine associated with artesunate and one dose level of ferroquine alone.
  • To assess pharmacokinetics parameters of ferroquine and its metabolites along sparse sampling schedules.

The overall study duration is 64 days, consisting of a screening period (less or equal 1 day), of a 3-day treatment period during which the patient is hospitalized for a maximum of 60 hours, and a follow-up period of 61 days.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Plasmodium Falciparum Infection
  • Drug: Ferroquine (SSR97193)

    Pharmaceutical form: capsule

    Route of administration: oral

  • Drug: Placebo

    Pharmaceutical form: capsule

    Route of administration: oral

  • Drug: artesunate

    Pharmaceutical form: tablets

    Route of administration: oral

  • Experimental: Ferroquine high dose + artesunate
    Ferroquine at 6 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
    • Drug: artesunate
  • Experimental: Ferroquine medium dose + artesunate
    Ferroquine at 4 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
    • Drug: artesunate
  • Experimental: Ferroquine low dose + artesunate
    Ferroquine at 2 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
    • Drug: artesunate
  • Experimental: Ferroquine alone at medium dose
    Ferroquine at 4 mg/kg/d OD alone for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
440
November 2010
November 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 3 cohorts enrolled in sequence with data interim review by Data Monitoring Committee (DMC) between cohort 1-2 and cohort 2-3

    • Cohort 1 : Adults > 50 kg or Adolescents >30 kg and age > or = 14 years
    • Cohort 2 : Children with body weight [30 kg- 15 kg[
    • Cohort 3 : Children with body weight [15 kg-10 kg]
  • Age related Body Mass Index (BMI)> or = 5 th percentile.
  • Presence of body temperature > or = 37.5°C or history of fever in the last 24 hours.
  • Monoinfection with Plasmodium falciparum with parasitemia from 1,000/microL to 200,000/microL.
  • Signed Informed Consent Form by the patient (if the patient is > or = age defining majority) or by the parents or legal guardian of minor patients (<18 years of age or < other age locally defining majority). In addition, participants with capacity for writing will sign off on an Assent Form. Patients with no capacity for writing will have the Assent Form read. In that case, an impartial witness will certify the document was read to the child.

Exclusion Criteria:

  • Presence of HBs antigen and of anti-HCV antibodies
  • Laboratory parameters with clinical significant abnormalities and/or reaching critical values : Hemoglobin (< 7g/dl), hematocrit, red blood cell count, white blood cell, reticulocytes, platelets, glucose, creatinine, aspartate transferase (AST), alanine transferase (ALT > 3 ULN), alkaline phosphatase, total bilirubine > 1.5 ULN.
  • History or presence of any clinically significant disease or symptoms which might confound the interpretation of the safety and efficacy information.
  • Splenectomized patients.
  • Presence of criteria for complicated malaria
  • Patients unable to drink
  • Breastfeeding patients.
  • Permanent vomiting.
  • Female participants with child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study (e.g. implants, oral contraceptives, some intra-uterine devices or a double barrier method). The need for an efficient method will be reminded to the patient and the patient's legal guardian(s) by the investigator.
  • Previous treatment within 5 times the elimination half-life or within the last 14 days, whichever the longest :

    • with any anti-malaria agents i.e., quinine, chloroquine, amodiaquine, mefloquine, halofantrine, sufladoxine-pyrimethamine, doxycycline-pyrimethamine, primaquine, artemether, atovaquone, proguanil, lumefantrine,
    • with an other investigational drug
    • with 2D6 main substrates
  • Past or concomitant participation in a study with an anti-malaria vaccine.
  • Measles vaccine injection within the last 15 days.
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
Benin,   Burkina Faso,   Cameroon,   Gabon,   Kenya,   Tanzania
 
NCT00988507
DRI10382
Yes
Trial Transparency Team, sanofi-aventis
Sanofi
Not Provided
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP