This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-
infection were randomized (1:1) to receive
pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg) or
chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with
pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with
chloroquine.
Pyronaridine was non-inferior to
chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%.
Pyronaridine-artesunate cure rates were non-inferior to
chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with
pyronaridine-artesunate (median 23.0 h) versus
chloroquine (32.0 h; p<0.0001), as was
fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum
infection incidence until Day 42 were 2.5% with
pyronaridine-artesunate, 6.1% with
chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum
infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with
pyronaridine-artesunate and 72/228 (31.6%) with
chloroquine. Mild and transient increases in hepatic
enzymes were observed for
pyronaridine-artesunate.
CONCLUSION: Clinicaltrials.gov NCT00440999.