Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients
Condition: Malaria
MeSH terms: Malaria; Malaria, Falciparum
Intervention: Pyronaridine artesunate; Coartem® (artemether lumefantrine)
Intervention description: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2); AL (20:120mg tablets) twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 1272.0
Sex: All
Minimum age: 3 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: malaria; antimalarial; artemisinin based combination therapy (ACT); P. falciparum; pyronaridine artesunate (Pyramax)

Summary:

      The primary objective of this phase III study is to compare the efficacy and safety of the
      fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of Coartem® (artemether
      lumefantrine, AL) in children and adults with uncomplicated P falciparum malaria in Africa
      and South East Asia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients between the age of 3 and 60 years, inclusive.

          -  Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.

          -  Presence of acute uncomplicated P. falciparum mono-infection confirmed by:

               1. Fever, as defined by axillary/tympanic temperature ≥ 37.5°C or oral/rectal
                  temperature ≥ 38°C, or documented history of fever in the previous 24 hours and,

               2. Positive microscopy of P. falciparum with parasite density between 1,000 and
                  100,000 asexual parasite count/μl of blood.

          -  Written informed consent, in accordance with local practice, provided by patient
             and/or parent/guardian/spouse.

          -  Ability to swallow oral medication.

        Exclusion Criteria:

          -  Patients with signs and symptoms of severe/complicated malaria requiring parenteral
             treatment according to the World Health Organization Criteria 2000.

          -  Mixed Plasmodium infection.

          -  Severe vomiting or severe diarrhoea.

          -  Known history or evidence of clinically significant disorders.

          -  Presence of significant anaemia, as defined by Hb <8 g/dL.

          -  Presence of febrile conditions caused by diseases other than malaria.

          -  Known history of hypersensitivity, allergic or adverse reactions to pyronaridine,
             lumefantrine or artesunate or other artemisinins.

          -  Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or
             hypomagnesaemia.

          -  Use of any other antimalarial agent within 2 weeks prior to start of the study as
             evidenced by a positive urine test.

          -  Female patients of child-bearing potential must be neither pregnant (as demonstrated
             by a negative pregnancy test) nor lactating, and must be willing to take measures to
             not become pregnant during the study period.

          -  Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6
             (flecainide, metoprol, imipramine, amitriptyline, clomipramine).

          -  Received an investigational drug within the past 4 weeks.

          -  Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen. (HBsAg) or
             Hepatitis C antibody (HCV Ab).

          -  Known seropositive HIV antibody.

          -  Liver function tests [ASAT/ALAT levels] >2.5 times the upper limit of normal range.

          -  Known significant renal impairment as indicated by serum creatinine >1.4 mg/dL.