Table 2 TCP-2
From: Designing the next generation of medicines for malaria control and eradication
TCP-2 criteria at phase IIa | Minimum essential | Ideal |
|---|---|---|
Dosing regimen; adult dose* | Oral, one-three doses; < 1500 mg | Oral, single dose; < 100 mg |
Rate of onset of action and Clinical Parasite Reduction Ratio (PRR) | Dependent on TCP-1 partner. Together with TCP-1 must deliver >95% cure | ≥12 log unit reduction in asexual blood stage load. Monotherapy cure |
Susceptibility to loss of efficacy due to acquired resistance | Low (better than atovaquone); no cross resistance with TCP-1 | Very low (similar to chloroquine); no cross resistance with TCP-1. Resistance markers identified |
Clinical efficacy from single dose (ACPR at day 28, per protocol) | >80% PCR-corrected | >95% non PCR-corrected |
Bioavailability / food effect - human | > 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 preclinical data from relevant G6PD deficient animal models | Measured - No enhanced risk in G6PD deficient subjects |
Formulation | Acceptable clinical formulation identified | |
Cost of single treatment | Similar to current medication: < $0.50 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) | ≥ 24 months | ≥ 5 years |