Pyronaridine Artesunate (3:1) in Children and Adults With Acute Plasmodium Vivax Malaria
Condition: Malaria
MeSH terms: Malaria; Malaria, Vivax
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to compare the efficacy and safety of the fixed combination of
      pyronaridine artesunate (Pyramax®, PA) (180:60 mg) with that of standard chloroquine therapy
      in children and adults with acute, uncomplicated Plasmodium vivax malaria.
    

Detailed description: 
      This is a multi-centre, randomised, double-blind, double-dummy, parallel-group,
      non-inferiority study comparing the efficacy and safety of the fixed combination of
      pyronaridine/artesunate (ie, PP/AS [PA]) (180:60 mg) with that of standard chloroquine
      therapy in children and adults with acute uncomplicated P. vivax malaria. The study
      population will include 456 patients, comprising male and female children (≥20 kg body
      weight) and adults recruited from study sites in South East Asia and India.

      Patients will be randomised in a 1:1 ratio to receive either oral PA (180:60 mg tablets) plus
      chloroquine-placebo or oral chloroquine (155 mg tablets).plus PA-placebo, once a day for 3
      consecutive days (Days 0, 1, and 2). For PA, posology was based on body weight ranges with
      subjects receiving 1 to 4 tablets depending on their body weight. The dose range covered by
      this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, which has been shown to be effective and
      safe in Phase I and II studies. The chloroquine daily dose is 10 mg/kg on Days 0 and 1 and 5
      mg/kg on Day 2 for children, and 620 mg on Days 0 and 1 and 310 mg on Day 2 for adults.

      Patients will be confined to the study facility for ≥4 days (Days 0,1,2 & 3) and ideally
      remain near the study site for ≥7 days, or once fever and parasite clearance has been
      confirmed for ≥24 hours - whichever occurs later.

      The primary efficacy end point for the study is the crude cure rate on Day 14, which is
      defined as the absence of P. vivax parasitaemia on Day 14. Scheduled follow-up visits will
      continue until completion of the study at Day 42. In the case of adverse events reported and
      unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution
      of the event.

      For patients who complete the study up to Day 28 and who have normal glucose-6-phosphate
      dehydrogenase (G-6-PD) activity, a 14-day course of primaquine (15 mg/day for adults and 0.3
      mg/kg/day for children) will be administered starting on Day 28 to complete their radical
      cure. Subjects who are deficient in G-6-PD and who completed the study up to Day 28 will be
      treated per country policy.
    

Intervention name(s): Pyronaridine artesunate; Chloroquine
Intervention type(s): Drug; Drug
Other intervention name(s): Pyramax
Intervention MeSH terms: Artesunate; Chloroquine; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Care Provider, Investigator)
Primary purpose: Treatment
Keywords: P vivax; malaria; artemisinin based combination therapy (ACT); antimalarial; pyronaridine artesunate (Pyramax)