Table 1 TCP-1
From: Designing the next generation of medicines for malaria control and eradication
TCP-1 criteria at human proof of concept | Minimum essential | Ideal |
|---|---|---|
Dosing regimen; adult dose* | Oral, one-three doses; <1,000 mg | Oral, single dose; <100 mg |
Rate of onset of action and clinical parasite reduction ratio from single dose | Immediate and rapid clearance of parasites at least as fast as chloroquine; > 6 log unit total reduction in parasites | Immediate and rapid clearance of parasites at least as fast as artesunate; > 6 log unit total reduction in parasites |
Susceptibility to loss of efficacy due to acquired resistance | Low (better than atovaquone); no cross resistance with TCP-2 | Very low (similar to chloroquine); no cross resistance with TCP-2. Resistance markers identified |
Clinical efficacy from single dose (day 7) including patients from areas known to be drug-resistant to current first line medications | 100% | |
Clinical efficacy from single dose (ACPR at day 28 or more, per protocol, PCR-corrected) | >50% | >95% |
Bioavailability /Food Effect - human data | >30%, <3-fold | >50%, none |
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 preclinical data from relevant G6PD deficient animal models | Measured - No enhanced risk in G6PD deficient subjects |
Formulation | Acceptable clinical formulation identified | |
Cost of active ingredient in final medicine | Similar to current medication: ≤$0.5 for adults, $0.1 for infants under two years | Similar to older medications: <$0.25 for adults, $0.05 for infants under two years |
Projected stability of final product under Zone IVb conditions (37°C 75% humidity) | ≥ 6–24 months | ≥1-5 years |