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Clinical Trial Summary

The observed changes of P. falciparum sensitivity to artemisinin lead to the intensification of early detection as well as treatment monitoring in malaria infection. It is widely accepted that the development of resistance can be delayed by the use of combination therapy, especially combinations that include artemisinin derivatives (acts). As the resistance problem is considered extremely serious; as a consequence, who has recommended that all monotherapy for malaria should be stopped.

Current WHO guidelines recommend that the drug combination regimens using ACT with effective partner medicines should be used to decrease the risk of development or spreading of artemisinin resistance.


Clinical Trial Description

Current WHO guidelines recommend that the drug combination regimens using ACT with effective partner medicines should be used to decrease the risk of development or spreading of artemisinin resistance.

Pyronaridine (PP) and artesunate (AS) are antimalarial agents with a history of clinical use both separately and in combination with other drugs. Each drug has powerful anti-schizonticidal actions. The action of artesunate is a rapid knock-down of the parasites, after which the drug is rapidly cleared as it has a short systemic half-life. Pyronaridine is also effective in the short-term but has an intermediate blood half-life thus providing a sustained schizonticidal effect. The aim of the fixed dose combination of pyronaridine and artesunate (PA or PYRAMAX®) in the treatment of uncomplicated acute malaria is to provide a rapid reduction in parasitemia with a short-term regimen, thereby improving compliance and reducing the risk of recrudescence through the slower elimination of pyronaridine. Doses have been selected to be in line with current prescribing practice for these agents when used as mono-therapy.

Primaquine (PQ) is an effective gametocytocide for P. falciparum transmission prevention and as tissue killing for the radical cure in P. vivax and P. ovale infection. It will be given only in the presence of other antimalarials, so it is necessary to study the drug interactions between primaquine, pyronaridine and artesunate. It is inevitable that in the near future, pyronaridine-artesunate (PA) and primaquine (PQ) combination treatment will become necessary. These drugs are metabolized by cytochrome P450 enzymes which potentially causes pharmacokinetic alteration and clinically significant drug-drug interactions that can lead to unanticipated adverse reactions or therapeutic failures because of the suboptimal exposure of the parasite.

This study is planned to evaluate potential pharmacokinetic interaction of orally administered primaquine and pyronaridine-artesunate (PYRAMAX®) in healthy adult subjects. The results of these interaction studies are important in order to provide clinical guidance for the optimum combination primaquine and pyronaridine-artesunate (PYRAMAX®) treatment regimens in malaria infections. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT01552330
Study type Interventional
Source University of Oxford
Contact
Status Completed
Phase Phase 1
Start date May 2012
Completion date October 2012

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