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

Plasmodium Falciparum Infection Clinical Trial

— FARM  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00988507
• Other study ID #: DRI10382
• Status: Terminated
• Phase: Phase 2
• First received: October 1, 2009
• Last updated: June 27, 2011
• Start date: October 2009
• Est. completion date: November 2010

Study information

• Verified date: June 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Institutional Ethical Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 440
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Plasmodium Falciparum Infection

Intervention

Drug:
• Ferroquine (SSR97193)
Pharmaceutical form: capsule Route of administration: oral
• Placebo
Pharmaceutical form: capsule Route of administration: oral
• artesunate
Pharmaceutical form: tablets Route of administration: oral

Locations

Country	Name	City	State
Benin	Sanofi-Aventis Investigational Site Number 204001	Cotonou
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
Cameroon	Sanofi-Aventis Investigational Site Number 120001	Yaounde
Gabon	Sanofi-Aventis Investigational Site Number 266001	B.P. 118 Lambarene
Gabon	Sanofi-Aventis Investigational Site Number 266002	Libreville
Kenya	Sanofi-Aventis Investigational Site Number 404001	Kilifi
Kenya	Sanofi-Aventis Investigational Site Number 404002	Kisumu
Tanzania	Sanofi-Aventis Investigational Site Number 834001	Korogwe

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Benin,  Burkina Faso,  Cameroon,  Gabon,  Kenya,  Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		4 weeks	No
Secondary	Cure rate at Day 28		4 weeks	No
Secondary	Parasite Clearance Time (Median).		up to 63 days	No
Secondary	Fever Clearance Time (Median)		up to 63 days	No
Secondary	Recrudescent infections at Day 28 in the ferroquine group in monotherapy		4 weeks	No
Secondary	Recrudescent infections at Day 63		9 weeks	No
Secondary	Adequate Clinical and Parasitological Response (ACPR) at D28		4 weeks	No