Pharmacokinetic and Pharmacodynamic Study of Mefloquine and Dihydroartemisinin-Piperaquine in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      This is an open-label sequential pharmacokinetic study in 16 healthy glucose-6-phosphate
      dehydrogenase (G6PD) normal Thai subjects at Faculty of Tropical medicine, Mahidol
      university.

      The 16 subjects have already participated in a healthy volunteer studies in the past either
      i) Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered
      primaquine and dihydroartemisinin-piperaquine (DHA-PQP) in Healthy Adult Subjects or ii)
      Comparison of the electrocardiographic effects in relation to Pharmacokinetic profile of
      chloroquine and piperaquine in healthy Thai subjects

      Every subject was administered a single dose of three tablets of DHA-PQP from previous
      studies. To avoid unnecessary exposure of DHA-PQP again, we propose to include the results of
      DHA-PQP arm from these previous studies and ask the healthy subjects to participate this
      study for receiving only single dose of three tablet of DHA-PQP (40mg/320mg) and two tablet
      of Mefloquine (250mg) on first admission and single dose of two tablet of Mefloquine on
      second admission.
    

Detailed description: 
      Artemisinin resistance poses the greatest threat to current global initiatives to control and
      eliminate malaria. The World Health Organisation recommends the use of the artemisinin
      combination therapy (one partner drug combine with artemisinin as the back bone) (ACTs)
      instead of the single drug. The reduction in artemisinin sensitivity has left partner drugs
      within ACTs exposed too much larger number of parasites and unsurprisingly cure rates with
      ACTs have begun to fall substantially.

      Recently, the Mahidol Oxford Tropical Medicine Research Unit (MORU) has applied for and
      received funding for an extension of the TRAC project. The proposed extension project, named
      TRACII, will further map artemisinin and partner drug resistance in the South-East Asian
      region. Also, TRACII aims to investigate the safety, pharmacokinetic characteristics and
      efficacy of a novel combination of an artemisinin-derivative and two long acting partner
      drugs, piperaquine and mefloquine.

      It is necessary that the potential drug-drug interactions of mefloquine and
      dihydroartemisinin-piperaquine (DHA-PQP) are characterized. Piperaquine and Mefloquine are
      both metabolized by Cytochrome P450 3A4 (abbreviated CYP3A4) enzyme which potentially results
      in clinically significant drug-drug interactions that can cause unanticipated adverse
      reactions or therapeutic failures because of the suboptimal drug exposures to the parasite.

      The study will evaluate the pharmacokinetic interaction and safety profile focusing on the
      cardiogenic effect (QTc prolongation) of this triple combinations of DHA-PQP and mefloquine.
      Piperaquine and Mefloquine are both metabolized by Cytochrome P450 3A4 enzyme which
      potentially results in clinically significant drug-drug interactions.

      These safety and pharmacokinetic data will be translated to support the intervention in the
      Tracking Resistance to Artemisinin Collaboration II (TRACII) project.

      This is an open-label sequential pharmacokinetic study in 16 healthy G6PD normal Thai
      subjects. The 16 subjects have participated in a healthy volunteer studies in the past either
      i) Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered
      primaquine and dihydroartemisinin-piperaquine in Healthy Adult Subjects or ii) Comparison of
      the electrocardiographic effects in relation to Pharmacokinetic profile of chloroquine and
      piperaquine in healthy Thai subjects in which they were administered a single dose of three
      tablets of DHA-PQP. To avoid unnecessary exposure of other healthy subjects to this study, we
      propose to include the result of these previous studies and ask the healthy subjects to
      participate from regimen 1 and onward.

      Subjects will be admitted in the inpatient ward to receive 2 drug regimens: regimen 1
      (Mefloquine with DHA-PQP) and regimen 2 (Mefloquine). Every subject will have 1 screening and
      2 admissions in the hospital
    

Intervention name(s): Mefloquine and Dihydroartemisinin-piperaquine; Wash-out period; Mefloquine
Intervention type(s): Drug; Other; Drug
Intervention description(s): 2 tablets of mefloquine and 3 tablets of dihydroartemisinin-piperaquine single dose; 2 tablets of Mefloquine single dose
Intervention MeSH terms: Piperaquine; Artenimol; Mefloquine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Mefloquine/Dihydroartemisinin-piperaquine; drug interaction