Efficacy and Tolerability of Artesunate Amodiaquine Versus Chloroquine in the Treatment of Uncomplicated Plasmodium Vivax Malaria

Study Overview
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Brief Summary
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Primary Objective: - To demonstrate the non-inferiority of corrected adequate clinical and parasitological response at Day 28 of Artesunate Amodiaquine (ASAQ) versus chloroquine Secondary Objectives: To assess the non inferiority on the same way as the main criteria: at Day 28 before corrected cure rate at Day 14 and Day 42 before and after corrected cure rate To compare the two groups of treatment in terms of: Efficacy: Proportion of aparasitaemic patients at 24, 48 an 72 hours Proportion of afebrile patients at 24, 48 and 72 hours Percentage of gametocyte carriers during follow-up Evolution of the mean of gametocytes during the 42 days of follow-up Evolution of haemoglobin value between Day 0 and Day 7, Day 0 and Day 28 Clinical and biological tolerability: Proportion of any adverse event Biological safety: haematology (Red blood cells, Haemoglobin, White Blood Cells, neutrophils, platelets), biochemistry (creatinine, transaminases (alanine amino transferase/ALT), bilirubins) ECG (electro encephalogram) (Day 0, Day 3,Day 28) only for patients 10 years old and above

Detailed Description
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Each patient will be followed for a period of 42 days

Official Title
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A Randomised Comparative Study to Assess the Efficacy and Tolerability of Blood Schizonticidal Treatments With Artesunate Amodiaquine Winthrop® / Coarsucam (ASAQ) Versus Chloroquine (CQ) for Uncomplicated Plasmodium Vivax Monoinfection Malaria

Conditions
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Malaria

Intervention / Treatment
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* Drug: ARTESUNATE + AMODIAQUINE
* Drug: Chloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adults and children over 6 months old and bodyweight > 5 kg Able to be treated by oral route Axillary temperature ≥ 37,5 C or history of fever during the previous 2 days Symptomatic biologically confirmed Plasmodium vivax mono-infection, with parasitemia from 250 to 100000 parasites /µl of blood Written informed consent of the patients and for children written informed consent of the parents/legal representative for children. Children able to understand the objectives and the risks of the study will sign an assent form. Exclusion criteria: Known project of leaving the investigator site area during the follow-up period (42 days) Hypersensitivity to one of the investigational medicinal products or to any of the excipients Intake of an antimalarial treatment in the previous 30 days History of hepatic and (or) haematological impairment during treatment with amodiaquine Blurred vision suggesting a retinopathy Presence of at least one danger sign of malaria Pregnant or breast-feeding women Women with childbearing potential not willing to use an effective contraceptive method(s) for the duration of the study Known severe concomitant or underlying disease The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: artesunate/amodiaquine<br>artesunate (AS) / amodiaquine (AQ) as fixed dose combination 1 tablet of AS 25mg/ AQ 67,5mg or AS 50mg/AQ 135mg or AS 100mg/ AQ 270mg or 2 tablets of AS 100mg/ AQ 270mg dose according to bodyweight Once daily 3 days of treatment | Drug: ARTESUNATE + AMODIAQUINE<br>* Pharmaceutical form: Route of administration:<br>|
| Active Comparator: chloroquine<br>150mg tablets 25mg/kg in 3 days (10mg/kg on day 1 and 7,5 mg/kg on days 2 and 3) dose according to bodyweight Once daily 3 days of treatment | Drug: Chloroquine<br>* Pharmaceutical form:tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of clinical and parasitological efficacy based on temperature and parasitemia after Polymerase chain reaction (PCR) correction |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of clinical and parasitological efficacy based on temperature and parasitemia before and after PCR correction at D14 and D42 and before PCR correction at D28 |  | up to a maximum of 42 days | 
| Number of patients without parasite |  | up to a maximum of 42 days | 
| Number of patients without fever |  | up to a maximum of 42 days | 
| Number of patients with gametocytes |  | up to a maximum of 42 days | 
| Change from baseline in Haemoglobin levels |  | Day 7, Day 28 | 
| Incidence and severity of adverse events collected |  | up to a maximum of 42 days | 
| ECG (QTc) changes in patients group aged >= 10 years from baseline |  | Day 3, Day 28 | 
| Assessment of biological tolerability (bilirubin, ALAT, Creatinine, Leukocytes, Neutrophils and platelets count) from baseline |  | up to a maximum of 42 days |