Pharmacokinetic Study of Primaquine and Dihydroartemisinin-Piperaquine in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The observed changes of P. falciparum sensitivity to artemisinin leads 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 artemisinin-based combination therapies (ACTs). The resistance problem is
      considered extremely serious and as the consequence WHO has recommended that all monotherapy
      for malaria should be stopped Current WHO guideline recommends the drug combination regimens
      using ACT with effective partner medicines to decrease the risk of development or spreading
      of artemisinin resistance.

      Dihydroartemisinin-piperaquine (DHA-PQP); the fixed-dose combination of Dihydroartemisinin
      (DHA) and Piperaquine phosphate (PQP) is now one of the recommended drugs by WHO as the oral
      treatment for uncomplicated P. falciparum. DHA-PQP composes of both blood schizonticidal
      drugs, with different mechanism of action and different half-life to improve the therapeutic
      efficacy and to prevent the development of drug resistance to the individual drug. Moreover,
      it is beneficial for the mutual protection against resistance and long lasting protection
      against new infection, due to long half-life of PQP.

      Primaquine is an effective gametocytocidal for P. falciparum transmission prevention and as
      tissue killing for the radical cure in Plasmodium vivax and Plasmodium ovale infection. It
      will be given only in the presence of other antimalarials, so it is necessary that the data
      of the potential drugs interaction of primaquine and DHA-PQP should be characterized. It is
      inevitable that in the near future, Dihydroartemisinin-piperaquine (DHA-PQP) and primaquine
      combination treatment becomes necessary. These drugs are metabolized by cytochrome P450
      enzyme which potentially causes pharmacokinetic alteration, resulting in clinically
      significant drug-drug interactions that can cause 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 (PQ) and dihydroartemisinin-piperaquine (DHA-PQP) in healthy adult
      subjects. The results of these interaction studies are important in order to provide clinical
      guidance for the optimum combination of primaquine and DHA-PQP treatment regimens in malaria
      infections.
    


Intervention name(s): A; B
Intervention type(s): Drug; Drug
Intervention description(s): Subject will receive primaquine (PQ) then receive dihydroartemisinin-piperaquine (DHA-PQP)after 1 week washout period and receive PQ together with DHA-PQP for the third regimen after 8 weeks washout period.
Primaquine:
1 tablet of primaquine phosphate contains: 26.3 mg (15 mg base)
Dosage: 2 tablets
DHA-PQP:
1 tablet of Eurartesim contains: DHA 40 mg: piperaquine 320 mg
Dosage: 3 tablets; Subject will receive primaquine (PQ) then receive PQ together dihydroartemisinin-piperaquine (DHA-PQP) after 1 week washout period and receive DHA-PQP for the third regimen after 8 weeks washout period.
Primaquine:
1 tablet of primaquine phosphate contains: 26.3 mg (15 mg base)
Dosage: 2 tablets
DHA-PQP:
1 tablet of Eurartesim contains: DHA 40 mg: piperaquine 320 mg
Dosage: 3 tablets
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment