Pyronaridine and Artesunate (3:1) in Children With Acute Uncomplicated Plasmodium Falciparum Malaria
Condition: Uncomplicated Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Intervention: Pyronaridine-Artesunate
Intervention description: Once a day for 3 days
Intervention MeSH terms: Artesunate; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 2 Years
Maximum age: 14 Years
Healthy volunteers: No
Keywords: malaria; P. falciparum; artemisinin based combination therapy (ACT); antimalarial; pyronaridine artesunate (Pyramax)

Summary:

      The purpose of this study is to evaluate three dose levels of a combination tablet and a
      fixed dose granule formulation of pyronaridine and artesunate (PA) for the treatment of acute
      uncomplicated falciparum malaria in children.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients presenting with symptoms of acute uncomplicated falciparum malaria with the
        following inclusion criteria:

          -  Male or female children, being between 2 and 14 years of age inclusive

          -  Weight between 10 and 40 kg inclusive

          -  Written informed consent, in accordance to local practice, provided by
             parent/guardian. If the parent/guardian is unable to write, witnessed consent is
             permitted according to local ethical considerations. Where possible, parent assent
             will be sought

          -  Absence of severe malnutrition (defined as mid upper arm circumference <110mm)

          -  Presence of acute symptomatic uncomplicated P. falciparum malaria with a diagnosis
             confirmed by a positive blood smear with asexual forms of P. falciparum only (i.e. no
             mixed infection) plus measured temperature of ≥37.5°C (depending on method of
             measurement as below) or history of fever within the past 24 hours :

          -  the acceptable range is between 1,000 and 200,000 asexual parasite count/μl of blood
             and

          -  axillary/tympanic temperature of ≥37.5°C or oral/rectal temperature of ≥38.0°C

          -  Females of childbearing potential are not allowed to be pregnant or lactating and must
             be willing to use adequate measures of contraception during the study period

          -  Ability to comply with the study visit schedule and the study protocol for the
             duration of the study

        Exclusion Criteria:

          -  Patients with signs and symptoms of severe/complicated malaria requiring parenteral
             antimalarial treatment according to the WHO Criteria 2000

          -  Mixed Plasmodium infection

          -  Severe vomiting, defined as >3 times in the 24 hours prior to inclusion in the study
             or inability to tolerate oral treatment, or severe diarrhoea defined as >3 watery
             stools per day

          -  Known history or evidence of clinically significant disorders such as cardiovascular
             (including arrhythmia, acute QTc interval greater or equal to 450 msec), respiratory
             (including active tuberculosis), hepatic, renal, gastrointestinal, immunological
             (including active HIV-AIDS), neurological (including auditory), endocrine, infectious,
             malignancy, psychiatric or other abnormality (including head trauma)

          -  Presence of febrile conditions caused by diseases other than malaria

          -  Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or
             artesunate or other artemisinins

          -  Use of any other antimalarial treatment within 2 weeks prior to start of the study as
             confirmed by Lignin test and Saker Solomon urine test

          -  For females of childbearing potential, positive urine pregnancy test or lactating

          -  Use of an investigational drug within the past 8 weeks

          -  Known active Hep A immunoglobulin, Hep B surface antigen, or Hep C antibody

          -  Known seropositive HIV antibody

          -  Liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase
             [ALT] levels) >3 times the upper limit of normal

          -  Known significant renal impairment as indicated by a serum creatinine ≥2 mg/dL

          -  Previous participation in this clinical study