Pharmacokinetic Study of Primaquine and Chloroquine in Healthy Subjects
Condition: Vivax Malaria
MeSH terms: Malaria, Vivax
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): A; B
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: primaquine; chloroquine; pharmacokinetic; interactions