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
  Purpose

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.

Condition Intervention Phase
Plasmodium Falciparum Infection
Drug: Ferroquine (SSR97193)
Drug: Placebo
Drug: artesunate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 440
Study Start Date: October 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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 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.
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 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.
Drug: Ferroquine (SSR97193)

Pharmaceutical form: capsule

Route of administration: oral

Drug: Placebo

Pharmaceutical form: capsule

Route of administration: oral


Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00988507

Locations
Benin
Sanofi-Aventis Investigational Site Number 204001
Cotonou, Benin
Burkina Faso
Sanofi-Aventis Investigational Site Number 854002
Bobo-Dioulasso 01, Burkina Faso
Sanofi-Aventis Investigational Site Number 854003
Nouna, Burkina Faso
Sanofi-Aventis Investigational Site Number 854001
Ouagadougou, Burkina Faso
Cameroon
Sanofi-Aventis Investigational Site Number 120001
Yaounde, Cameroon
Gabon
Sanofi-Aventis Investigational Site Number 266001
B.P. 118 Lambarene, Gabon
Sanofi-Aventis Investigational Site Number 266002
Libreville, Gabon
Kenya
Sanofi-Aventis Investigational Site Number 404001
Kilifi, Kenya
Sanofi-Aventis Investigational Site Number 404002
Kisumu, Kenya
Tanzania
Sanofi-Aventis Investigational Site Number 834001
Korogwe, Tanzania
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Trial Transparency Team, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00988507     History of Changes
Other Study ID Numbers: DRI10382
Study First Received: October 1, 2009
Last Updated: June 27, 2011
Health Authority: France: Institutional Ethical Committee

Additional relevant MeSH terms:
Malaria, Falciparum
Malaria
Parasitic Diseases
Protozoan Infections
Artesunate
Amebicides
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014