Table 4 TCP-4
From: Designing the next generation of medicines for malaria control and eradication
TCP-4 criteria | Minimum essential | Ideal |
|---|---|---|
Dosing regimen; adult dosea | Oral, once per week; < 1,000 mg | Oral, once per month; < 100 mg |
Rate of onset of action | Slow onset of action (>48 h) against asexual blood stages or causal liver stage activity | |
Susceptibility to loss of efficacy due to acquired resistance | Very low risk for blood stage | Very low; orthogonal mechanism to treatment use |
Clinical protection from infection | >95% protection from primary Plasmodium infection | >95% protection from all Plasmodia infections (including relapses) |
Transmission reduction to the mosquito vector: inhibition of oocysts via vector stage targeting at trough levels | No | > 90% |
Bioavailability /Food Effect - human data | > 30%, < 3-fold food effect | >50%, no food effect |
Drug-Drug Interactions | No unmanageable risks | No interactions with other anti-malarial, anti-retroviral or TB medicines |
Safety – Clinical | Acceptable therapeutic ratio based on human volunteer studies between exposure at human effective dose and NOAEL, dependent on nature of toxicity) | Therapeutic ratio >50 fold based on human volunteer studies between exposure at human effective dose and NOAEL; benign safety signal |
G6PD (Glucose-6-phosphate dehydrogenase) deficiency status | Measured - No enhanced risk in relevant G6PD deficient animal models | Measured - No enhanced risk in G6PD deficient subjects |
Formulation | Acceptable clinical formulation identified | |
Cost of single treatmentb | ≥ $0.5 for adults, $0.1 for infants under two years | < $0.25 for adults, $0.05 for infants under two years |
Projected stability of final product under Zone IVb conditions (37°C 75% humidity) | ≥ 2 years | ≥5 yr |