Pharmacokinetic Study of Primaquine and Dihydroartemisinin-Piperaquine in Healthy Subjects

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.

Conditions

• Healthy

Interventions

DRUG

A

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

DRUG

B

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

Sponsors & Collaborators

• University of Oxford

  lead OTHER

Principal Investigators

• Sasithon Pukrittayakamee, MD · Mahidol University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-06-30

Primary Completion

2012-09-30

Completion

2012-09-30

Countries

• Thailand

Study Locations