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. |