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Table 5 TPP-1 for the treatment of uncomplicated malaria in children and adults

From: Designing the next generation of medicines for malaria control and eradication

Parameter to be demonstrated for the combination in clinical evaluation

Minimum essential

Ideal SERCaP

Rate of onset of action

At least one component acts rapidly; patient fever decreased at 24 h

Both components act immediately; patient fever decreased within 24 h

Proportional Reduction in Parasite Load

>12 log unit reduction in asexual blood stage load

 

Clinical efficacy (day 7) including patients from areas known to be drug-resistant to current first-line medications

100%

100%

Clinical efficacy (ACPR at day 28 or later, per protocol)

>95% PCR-corrected

> 95% non PCR-corrected

Transmission blocking

No: preclinical models still need to be validated as predictors of clinical outcome

Yes

Relapse prevention: prevents the relapse of P vivax, and by inference P ovale.

No: preclinical models still need to be validated as predictors of clinical outcome

Yes

Confirmation in clinical studies capable of distinguishing prevention from delay

Bioavailability/ Food Effect

>30% for each molecule, <3-fold

>50% for each molecule, none

Drug-drug interactions

No unmanageable risk in terms of solid state or pharmacokinetic interactions

No risks in terms of solid state or pharmacokinetic interactions

Dosing regimen

Oral, two-three doses

Oral, once

Safety

Few drug related SAEs in phase III

No drug related SAEs; minimal drug-related AEs

Use in patients with G6PD deficiency

Testing not obligatory due to low risk

No enhanced risk

Pregnancy

Not contra-indicated in second and third trimester

Not contra-indicated

Formulations

Co-formulated tablets or equivalent, with taste masking for pediatrics

Co-formulated tablets for adults. Dispersible or equivalent with taste masking for pediatrics

Cost of treatment course

≤ $1.00 for adults, $0.25 for infants under two years

 

Shelf life of formulated product (ICH guidelines for Zones III/IV; combination only)

≥ 2 years

≥ 5 yr

Susceptibility to loss of efficacy due to acquired resistance

Low (better than atovaquone or pyrimethamine monotherapy); no cross resistance

Very low (similar to artemisinin or chloroquine); no cross resistance. Resistance markers identified.