Table 6 TPP-2 for a new medicine for chemoprotection
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 SEC |
|---|---|---|
Dosing regimen | Oral, once per week | Oral, once per month |
Rate of onset of action | For asexual blood stage action – slow onset (48 h) - before rapid killing | |
Clinical efficacy | Prevents primary infection of Plasmodium >95% | Prevents Plasmodium infection including relapse >95% |
Transmission blocking | No | Yes |
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 |
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 | Very low; no cross resistance with partner | Very low; no cross resistance and orthogonal mechanism from those used in treatment |