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Table 5 TPP-1 for the treatment of uncomplicated malaria in children and adults

From: Designing the next generation of medicines for malaria control and eradication

Parameter to be demonstrated for the combination in clinical evaluation Minimum essential Ideal SERCaP
Rate of onset of action At least one component acts rapidly; patient fever decreased at 24 h Both components act immediately; patient fever decreased within 24 h
Proportional Reduction in Parasite Load >12 log unit reduction in asexual blood stage load  
Clinical efficacy (day 7) including patients from areas known to be drug-resistant to current first-line medications 100% 100%
Clinical efficacy (ACPR at day 28 or later, per protocol) >95% PCR-corrected > 95% non PCR-corrected
Transmission blocking No: preclinical models still need to be validated as predictors of clinical outcome Yes
Relapse prevention: prevents the relapse of P vivax, and by inference P ovale. No: preclinical models still need to be validated as predictors of clinical outcome Yes
Confirmation in clinical studies capable of distinguishing prevention from delay
Bioavailability/ Food Effect >30% for each molecule, <3-fold >50% for each molecule, none
Drug-drug interactions No unmanageable risk in terms of solid state or pharmacokinetic interactions No risks in terms of solid state or pharmacokinetic interactions
Dosing regimen Oral, two-three doses Oral, once
Safety Few drug related SAEs in phase III No drug related SAEs; minimal drug-related AEs
Use in patients with G6PD deficiency Testing not obligatory due to low risk No enhanced risk
Pregnancy Not contra-indicated in second and third trimester Not contra-indicated
Formulations Co-formulated tablets or equivalent, with taste masking for pediatrics Co-formulated tablets for adults. Dispersible or equivalent with taste masking for pediatrics
Cost of treatment course ≤ $1.00 for adults, $0.25 for infants under two years  
Shelf life of formulated product (ICH guidelines for Zones III/IV; combination only) ≥ 2 years ≥ 5 yr
Susceptibility to loss of efficacy due to acquired resistance Low (better than atovaquone or pyrimethamine monotherapy); no cross resistance Very low (similar to artemisinin or chloroquine); no cross resistance. Resistance markers identified.