Phase II Dose-ranging Study of Pyronaridine/Artesunate in Adults Patients With Plasmodium Falciparum Malaria
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Intervention: pyronaridine/artesunate
Intervention description: Tablets of fixed dose combination of pyronaridine and artesunate at a ratio of 3:1. The tablets were taken daily for 3 days.
Intervention MeSH terms: Artesunate; Pyronaridine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 477.0
Sex: All
Minimum age: 15 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: malaria; antimalarial; artemisinin based combination therapy (ACT); pyronaridine artesunate (Pyramax)

Summary:

      The primary trial objective is to determine the clinically effective dose of orally
      administered pyronaridine/artesunate (Pyramax®, PA) with a 3:1 ratio to treat adults with
      acute, symptomatic, uncomplicated P. falciparum malaria in South East Asia and Africa.
      Secondary trial objectives are to determine the safety of once-daily dosing for 3 days of PA
      and to explore possible ethnic differences in safety or efficacy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients between the age of 15 and 60 years of age inclusive

          2. Written informed consent, in accordance with local practice, provided by patient
             and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is
             permitted according to local ethical considerations

          3. Absence of severe malnutrition (defined as the weight-for-height being below -3
             standard deviations or <70% of the median of the NCHS/WHO normalized reference values)

          4. Weight of between 35 kg and 75 kg inclusive

          5. 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 history of fever within the previous 24 hours or a measured
             temperature of ≥37.5°C (depending on method of measurement):

               -  the acceptable range is between 1,000 and 100,000 asexual parasite count/μl of
                  blood and

               -  axillary/tympanic temperature of ≥ 37.5°C or oral/rectal temperature of ≥ 38.0°C

          6. Ability to swallow oral medication

          7. Ability to comply with study visit schedule: patients will be hospitalised for at
             least 4 days and will be required to remain in the vicinity of the trial site for a
             minimum of 7 days or until clearance of fever and parasite for at least 24 hours,
             whichever is the later. The patient is to return to the study site or to make
             themselves available for all scheduled follow up visits, until discharge at Day 42.

          8. Females must not be pregnant or lactating and be willing to take measures to not
             become pregnant during the study period

          9. Willingness and ability to comply with the study protocol for the duration of the
             study

        Exclusion Criteria:

          1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral
             treatment according to the World Health Organization Criteria 2000

          2. Mixed Plasmodium infection

          3. Severe vomiting, defined as >3 times in the 24 hours prior to inclusion in the trial
             or inability to tolerate oral treatment

          4. Known history or evidence of clinically significant disorders such as cardiovascular
             (including arrhythmia), respiratory (including active tuberculosis), hepatic, renal,
             gastrointestinal, immunological (including active HIV-AIDS), neurological (including
             auditory), endocrine, infectious, malignancy, psychiatric or other clinically
             important abnormality (including head trauma).

          5. Presence of febrile conditions caused by diseases other than malaria

          6. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or
             artesunate or other artemisinins

          7. Evidence of use of any other antimalarial agent within 2 weeks prior to the start of
             the study confirmed by a negative urine test or using Eggelte dipsticks

          8. Positive urine pregnancy test or lactating

          9. Received an investigational drug within the past 4 weeks

         10. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or
             Hepatitis C antibody (HCV Ab)

         11. Known seropositive HIV antibody

         12. Liver function tests [ASAT/ALAT levels] >2.5 times upper limit of normal values

         13. Known significant renal impairment as indicated by a serum creatinine of ≥ 1.4 mg/dl

         14. Previous participation in this clinical trial