Table 1 Critical characteristics of four potential antimalarial drug candidates

Potential partner drug?

Ferroquine

Solid dispersion formulation-lumefantrine

Piperaquine ferroquine

Piperaquine

Drug half-life (h)

21

48–60

46–62

2–4

Efficacy

PCt1/2 0.9 h

PCt1/2 3.5 h

PC1/2 = 4.4 (WT K13) PC1/2 = 5.5 (Mutant)

Median PCt = 24 h same as coartem

PCR-corrected ACPR on day 42 was under 50% with single dose piperaquine

PCR-corrected ACPR on day 42 was >98% in both groups

Transmission blocking

Reduction in stage 5 gametocyte in vitro and inhibit oocyst development in standard membrane feeding assay

Reduction in stage 5 gametocyte in vitro and inhibit oocyst development in standard membrane feeding assay

7 patients with pre-treatment and 10 patients with post-treatment Pf gametocytes; one had up to day-6

Day 7 and Day 14 carriage higher than coartem [23]

Adverse event

Raised transaminase (3/21 patients)

Raised transaminase (30% of patients)

12/82 patients increased CPK

6.9% (49) got QTcF > 500 ms compared to 1.7% (6) in coartem

7/82 patients increased transaminases

2/82 patients QTcF > 450 ms. 18/82 patients with prolongation of QTcF > 30 ms from baseline

Resistance

SNP at PfATP4 gene can be selected in vitro after 4-months exposure to incremental increasing conc. of KAE

SNP at PfCARL gene can be selected in vitro after 4-months exposure to incremental increasing conc. of KAF

Slower PCt1/2 in K-13 mutation even though in vitro RSA suggested no difference

Not tested

MIC

0.1 ng/ml

4.1 ng/ml [17]