NCT01218932

Pharmacokinetic Study of Primaquine and Chloroquine in Healthy Subjects

Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Chloroquine in Healthy Thai Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

This is a standard pharmacokinetic interaction study. Subjects will be randomized to be either group A or B. Group A. Subjects will have 3 hospitalizations to complete. Each hospitalization will be about 12-24 hours depends on each regimen. Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period. Subjects in B group who receive regimen 1 of primaquine (PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission(visit 4) with 8 week wash out period in between.

Detailed description

Chloroquine and primaquine, has been first therapy for Plasmodium vivax and ovale malaria for over 50 years, and has been part of National policy in Thailand for decades. Primaquine is the only available hypnozoitocidal drug for P.vivax and gametocytocidal agent for Plasmodium falciparum malaria. Despite this enormous use knowledge about the mechanism of activity, pharmacokinetic properties, resistance and toxicity of primaquine are limited. Primaquine at the previously used dose for radical cure (15 mg base/day for 14 days) is also weakly effective against asexual stages of P. vivax malaria \[4\] The higher dose of 30 mg daily evaluated for malaria prophylaxis is now also generally recommended for radical cure. In the standard radical cure regimen, primaquine is usually given after the 3-day course of chloroquine, but there has been no study to inform timing of dosing so this decision is arbitrary. Despite the multistage specificity against the malaria parasite, and extensive recommendations, primaquine is currently underused because of uncertainties over safety, efficacy and dosage. Primaquine is an oxidant drug and causes haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Although several studies of the metabolites of the primaquine and chloroquine have been conducted over the past few years remarkably little is known about the interaction between these two commonly coadministered drugs. This study is open-label pharmacokinetic study. Healthy 16 volunteers will be recruited to the established volunteer facility at single site at the Hospital for Tropical Diseases to determine the pharmacokinetic properties of primaquine and it's main active metabolites and evaluate any interaction with chloroquine.in order to provide clinical guidance for the optimum primaquine/chloroquine treatment regimens.

Conditions

• Vivax Malaria

Interventions

Type	Name	Description
DRUG	A	Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period.
DRUG	B	Subjects in B group who receive regimen 1 of primaquine ( PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission( visit 4) with 8 week wash out period in between.

Timeline

• Start date: 2010-10-01
• Primary completion: 2011-10-01
• Completion: 2012-03-01
• First posted: 2010-10-11
• Last updated: 2012-06-14

Locations

1 site across 1 country: Thailand