Cohort Event Monitoring Study of Pyramax®

Study Overview
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Brief Summary
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The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. The study is to assess the safety of Pyramax, particularly in patients with underlying liver function abnormalities, in patients who have co-morbid conditions, such as HIV, and also in very small children (<1 year of age).

Detailed Description
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This is a non-comparative Cohort Event Monitoring study. The study will assess the safety of Pyramax in terms of the evaluation and identification of the hepatic safety events in a sub group of patients enrolled with liver function tests (LFT)s >2x upper limit of normal (ULN) from blood taken immediately prior to treatment without any clinical signs or symptoms of hepatotoxicity and with signs and symptoms of uncomplicated malaria confirmed by a Rapid Diagnostic Test (RDT) or microscopy (thick blood smear). The study will compare the clinical hepatic safety of Pyramax between a cohort of patients enrolled with LFTs >2xULN and a cohort of patients enrolled with normal LFTs matched for demographic characteristics. An estimated 8,572 malaria episodes are to be recruited to provide 120 malaria episodes in patients with baseline raised LFTs >2xULN for follow up of liver function. A cohort of at least 2% of children who are <1 year of age will be included for monitoring of liver function.

Official Title
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Phase IIIb/IV Cohort Event Monitoring Study To Evaluate, In Real Life Setting, The Safety And Tolerability In Malaria Patients Of The Fixed-Dose Artemisinin-Based Combination Therapy Pyramax®

Conditions
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Malaria,Falciparum

Intervention / Treatment
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* Drug: pyronaridine artesunate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations: Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children. Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear). analysis). Weight ≥5 kg - < 20 kg (granules); ≥20 kg (tablets). Ability to take an oral medication. Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country. The patient has to comply with all scheduled follow-up visits. Exclusion Criteria: Patients with clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4). Known allergy to artemisinin and/or to pyronaridine. Known pregnancy. Lactating women should be excluded if other anti-malarial treatments are available. Complicated malaria as per WHO definition (Annex 2) Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study. Patients having been treated with Pyramax in the previous 28 days.

Ages Eligible for Study
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Minimum Age: 3 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyramax<br>Pyronaridine artesunate tablets (180/60mg) and granules (60/20mg) | Drug: pyronaridine artesunate<br>* Antimalarial treatment<br>* Other names: Pyramax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation and identification of hepatic safety events, including raised liver function tests | Evaluation and identification of hepatic safety events (including raised liver function tests - LFTs) of Pyramax in a sub group of malaria patients enrolled with LFTs >2xUL. | Assessment up to Day 28. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall safety | Evaluation of the adverse event reporting of Pyramax in the treatment of uncomplicated malaria under real life conditions. | Assessment up to Day 28. | 
| Evaluation of Efficacy | Evaluation of the efficacy based on crude Day 28 cure rate by species and PCR adjusted cure rate for Day 28 cure rate for P. falciparum of Pyramax in the treatment of uncomplicated malaria under real life conditions | Assessment up to Day 28. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pyramax, Uncomplicated Malaria, Pyronaridine artesunate