Pharmacokinetic and Mosquito-Lethal Effects of Ivermectin (IVM), Primaquine (PQ), Dihydroartemisinin-Piperaquine (DHA-PQP) and Albendazole (ABZ) in Healthy Subjects
Condition: Drug Combination; Pharmacokinetics; Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Primary Objective

        -  To evaluate the safety and tolerability of co-administered single dose
           Dihydroartemisinin-Piperaquine (DHA-PQP), Ivermectin (IVM), Primaquine (PQ), and
           Albendazole (ABZ) in healthy subjects.

      Secondary Objectives

        -  To characterize the potential pharmacokinetic interactions between DHA-PQP, IVM, PQ, and
           ABZ in healthy adult subjects.

        -  To characterize the pharmacokinetic properties of PQ (and its major metabolite),
           DHA-PQP, IVM, and ABZ (and its major metabolite) when given alone and in combination.

        -  To investigate pharmacogenetic polymorphisms affecting drug levels of PQ, DHA-PQP, IVM,
           ABZ and their metabolites.

        -  To determine mosquito lethal efficacy of IVM, PQ, ABZ, and DHA-PQP combinations against
           Anopheles dirus and Anopheles minimus.

        -  To determine if IVM concentrations in venous blood differs from capillary blood.
    

Detailed description: 
      This is an open-label, sequential pharmacokinetic study in 16 healthy glucose-6-phosphate
      dehydrogenase (G6PD) normal Thai subjects. These 16 subjects have previously participated in
      either study:

        1. Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally
           Administered Primaquine (PQ) and Dihydroartemisinin-Piperaquine (DHA-PQP) in Healthy
           Adult Subjects (TMEC 12-004 (OxTREC ref. 58-11)) or study

        2. Comparison of the electrocardiographic effects in relation to Pharmacokinetic profile of
           chloroquine (CQ) and piperaquine (PQ) in healthy Thai subjects (TMEC 14-022 (OxTREC ref.
           39-14)) or

        3. subjects who not previously participated in study "TMEC 12-004 (OxTREC ref. 58-11)" and
           study "TMEC 14-022 (OxTREC ref. 39-14)".

      The study team will use the results of DHA-PQP regimen of the subjects from the above
      mentioned studies to compare with combination regimens in this study. This is to avoid
      unnecessary exposure of Subjects from (TMEC 12-004 (OxTREC ref. 58-11)) and (TMEC 14-022
      (OxTREC ref. 39-14)) to the subjects. In addition, subjects have previously been tested for
      G6PD deficiency during screening process from the above mentioned study with result showed as
      normal. Therefore, a G6PD deficiency test is not needed. A G6PD deficiency test is needed for
      subjects who not previously participated in study subjects who not previously participated in
      study "TMEC 12-004 (OxTREC ref. 58-11)" and study "TMEC 14-022 (OxTREC ref. 39-14)" for this
      study.

      Subjects will be admitted in the inpatient ward to receive single dose of 6 regimens
      (regimens 1-4 and 8-9) described below. Every subject will have at least 6 admissions in the
      hospital.

      1: IVM (400 μg/kg) via 6 mg tabs, w-o** >4wks; 2: IVM (400 μg/kg)+PQ (15 mg): 2 tabs), w-o
      >4wks; 3: IVM (400 μg/kg)+DHA-PQP (40mg/320 mg): 3 tabs), w-o >8wks; 4: IVM (400
      μg/kg)+DHA-PQP+PQ, w-o >8wks; 5*#: PQ (15 mg): 2 tabs, w-o > 2wks; 6#: DHA-PQP (40mg/320 mg):
      3 tabs, w-o >8wks; 7*#: DHA-PQP (40mg/320 mg): 3 tabs +PQ (15 mg): 2 tabs, w-o >8wks; 8: ABZ
      (200 mg) 2 tabs, w-o >2wks; 9: IVM (400 μg/kg)+DHA-PQP (40mg/320 mg): 3 tabs+PQ (15 mg): 2
      tabs +ABZ (400 mg): 1 tab, w-o >8wks

      * The subjects from TMEC-14-022 (OxTREC ref. 39-14) will have two additional admissions to
      receive two additional regimen PQ, and DHA-PQP with PQ

      # Subjects who not previously participated in study "TMEC 12-004 (OxTREC ref. 58-11)" and
      study "TMEC 14-022 (OxTREC ref. 39-14)" will have three additional admissions to receive
      three additional regimens PQ, DHA-PQP, and DHA-PQP with PQ.

      **w-o = washout period
    

Intervention name(s): IVM, IVM and PQ, IVM and DHA-PQP, IVM and DHA-PQP and PQ; PQ and DHA-PQP and PQ; DHA-PQP
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Regimen 1: IVM; Regimen 2: IVM and PQ; Regimen 3: IVM and DHA-PQP; Regimen 4: IVM and DHA-PQP and PQ;; Regimen 5: PQ; Regimen 7: DHA-PQP and PQ; Regimen 6: DHA-PQP
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug combination; Ivermectin; Primaquine; Dihydroartemisinin-Piperaquine; Albendazole; Pharmacokinetics; Mosquito-Lethal Effect; Healthy adult subject