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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
  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.