Conditions: Malaria
Keywords: Artemisinin-based combination therapy (ACT) Pyramax Pyronaridine artesunate Chloroquine Children Adults Plasmodium vivax Republic of Korea
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 30
Healthy volunteers: no

Brief summary:
The primary objective of this clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax (P. vivax) malaria

Detailed description:
This is a multi-centre, randomised, double-blind, double-dummy, parallel group, comparative trial. It is a Phase III study designed to meet the regulatory requirements for registration of pyronaridine artesunate (PA) in Korea. Chloroquine will be used as a comparator, which is recognized as an effective and well-tolerated anti-malarial therapy, and is standard blood-stage therapy for patients with P. vivax malaria in Korea. This study will be conducted in a total of 40 male and female children (≥20 kg body weight) and adult patients suffering from acute symptomatic uncomplicated P. vivax malaria recruited from study sites in Korea.

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 will be based on body weight ranges, with patients receiving 1 to 4 tablets per day depending on their body weight. The actual dose range covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg per day, 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, and 3) and 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. 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.

It is anticipated that the study results will be pooled with the results of study SP-C-006-06 entitled "A Phase III Comparative (Double-blind, Double-dummy) Randomized Multicentre Study to Assess the Safety \& Efficacy of Oral Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children \& Adult Patients with Acute Vivax Malaria " for a formal non-inferiority analysis.

Arms:
arm 1: Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.

For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy. arm 2: Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.

For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.

Interventions: intervention 1: Pyronaridine - artesunate intervention 2: Chloroquine
Intervention descriptions: intervention 1: Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days. intervention 2: Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.

Protocol document: