A Pharmacokinetic/Pharmacodynamic Study of Eurartesim Dispersible Formulation in Infants With P.Falciparum Malaria
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 2

Summary: 
      There is a need for paediatric formulations that permit accurate dosing and enhance patient
      compliance. However, for the treatment of malaria, scarce paediatric-friendly formulations
      are available on the market. Thus, a new water dispersible formulation of eurartesim has been
      developed for oral administration.

      Aim of this study is to provide data on pharmacokinetic profile, safety and efficacy of this
      new paediatric formulation and compare it with the crushed film coated tablet in infant
      patients (6 to ≤12 months of age) suffering from uncomplicated Plasmodium falciparum malaria.

      Furthermore, a Pharmacokinetic/Pharmacodynamic(PK/PD) modelling will be built up to establish
      PK/PD relationship in adult and paediatric populations.
    

Detailed description: 
      Although the significant advances made during the last decades in controlling malaria in
      Africa, morbidity and mortality in sub-Saharan countries remain substantial. It is estimated
      that around 655.000 deaths a year still occur due to malaria infection and the majority of
      such deaths occur among young African children.

      In response to the emergence and spread of classical drug-resistant Plasmodia strains, the
      WHO recommends since 2004 the use of artemisinin-based combination therapies (ACTs) in the
      treatment of uncomplicated malaria episodes.

      The artemisinin derivatives are currently the most rapidly acting and potent antimalarial
      drugs.

      Eurartesim is a fixed-dose combination product composed of dihydroartemisinin (DHA) and
      piperaquine phosphate (PQP). This second compound assures the long-term efficacy of
      eurartesim completing the whole body cleaning from the parasites. Eurartesim appears to offer
      benefits over existing licensed malaria treatments and is in line with current WHO treatment
      policy recommendations.

      Eurartesim obtained a centralized marketing authorization by the European Union as film
      coated tablets containing 160 mg PQP/20 mg DHA and 320 mg PQP/40 mg DHA. The drug, licensed
      for its use in children (above 6 months of age) and adults has been administered in infants
      (above 6 months) and young children by crushing the tablets and administering them with a
      small amount of water.

      According to the Guidelines on Clinical Investigation of Medicinal Products in the Paediatric
      Population (EMA ICH Topic E 11), there is a need for paediatric formulations that permit
      accurate dosing and enhance patient compliance.

      However, for the treatment of malaria, scarce paediatric-friendly formulations are available
      on the market, and this is a particularly blatant problem as young children carry the brunt
      of the malaria burden. Thus, a new water dispersible formulation of eurartesim has been
      developed for oral administration, since liquid formulations may be needed or desirable for
      paediatric patients of smaller ages due to their inability to swallow tablets. Moreover, in
      order to increase paediatric compliance to treatment, the new formulation is prepared with
      acceptable flavour and sweetener for children.

      Eurartesim is a promising effective ACT treatment for malaria. It provides a simple dosing
      scheme (a single daily dose over 3 days) and it does not need any concomitant administration
      of food to improve its absorption. Moreover, eurartesim offers an interesting post-treatment
      prophylactic effect following therapy, reducing the risk of new infection, an issue of
      particular relevance in highly endemic malaria countries.
    

Intervention name(s): Eurartesim dispersible oral tablet; eurartesim film coated tablet
Intervention type(s): Drug; Drug
Intervention description(s): The first dose of Eurartesim dispersible oral tablet will be administered immediately after randomization. the other two doses will be administered with an interval of 24 hours. Eurartesim tablet will be dispersed in about 10 mL of water.; The first dose of Eurartesim film coated tablet will be administered immediately after randomization. the other two doses will be administered with an interval of 24 hours. tablet will be crushed and dispersed in a few amount of water (about 10 ml).
Other intervention name(s): Piperaquine tetraphosphate plus dihydroartemisinin; Piperaquine tetraphosphate plus dihydroartemisinin
Intervention MeSH terms: Piperaquine; Artenimol; Artemisinins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Plasmodium falciparum Malaria; Eurartesim; ACT