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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
  1. *As discussed in the text, should frontline therapies be lost due to reduced efficacy or tolerability then a regimen over 3 days of dosing of novel well tolerated candidates that overcome any resistance will be acceptable.