A Single Dose Study to Assess the Regional Absorption and Bioavailability of 100mg GSK2190915A
Condition: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that
      attenuates the production of leukotrienes through the blockage of the first step in the
      leukotriene pathway, 5-lipoxygenase (5-LO) activation. GSK2190915 inhibits the production of
      leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs).

      This is an open label, 4-way, 4-treatment period, non-randomised, crossover study with an
      interim analysis. The GSK2190915 formulations used in this study will be: a 100mg and 200mg
      milled tablet, a 100mg enteric-coated tablet, and a [14C] radiolabelled GSK2190915
      intravenous solution.

      This study aims to determine the pharmacokinetics and absolute bioavailability of GSK2190915
      to enable optimisation of suitable formulations to be used in clinical development Fourteen
      subjects will be dosed to ensure data in 10 at the end of the clinical study. Seven of the
      subjects will receive an IV microtracer in addition to the other treatments.
    

Detailed description: 
      GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that
      attenuates the production of leukotrienes through the blockage of the first step in the
      leukotriene pathway, 5-lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory
      molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in
      response to allergic or inflammatory stimuli. GSK2190915 inhibits the production of
      leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs).

      This is an open label, 4-way, 4 treatment period, non-randomised, single-dose crossover study
      with an interim analysis following the third treatment period. The GSK2190915 formulations
      used are: milled 100mg and 200mg tablets, a 100mg enteric-coated tablet, and a [14C]
      radiolabelled GSK2190915 intravenous solution.

      There will be 4 periods. Period 1 includes two cohorts (of 7 subjects each), both of which
      will be administered the 100mg GSK2190915 milled tablet orally; however, the second cohort
      will in addition be dosed with an intravenous radiolabelled infusion of the drug. In the
      second period, a 100mg dose of milled GSK2190915 tablet (a ground half of a 200mg tablet) is
      administered directly to the proximal small bowel using an Enterion capsule. The same dose is
      repeated in the third period, but is administered directly to the distal small bowel. An
      interim analysis will then follow. The decision to proceed will be made following a review of
      the pharmacokinetic data from the first three treatments. In the fourth and final period, the
      treatment will be a 100mg enteric-coated tablet of GSK2190915 administered orally. There will
      be a minimum washout of 7 days in between each period.

      This study aims to determine the pharmacokinetics and absolute bioavailability of GSK2190915
      to enable optimisation of suitable formulations to be used in clinical development. Periods 1
      to 3 will characterise the absolute bioavailability of GSK2190915 using IV tracer and oral
      formulation, in addition to defining the regional absorption characteristics of the drug when
      released in the proximal and distal parts of the gastro-intestinal tract. The fourth period
      will investigate the oral bioavailability of an enteric coated formulation of GSK2190915.

      Fourteen subjects will be dosed to ensure data in 10 at the end of the clinical study. Seven
      of the subjects (in cohort 2, Period 1) will receive an IV microtracer in addition to the
      other treatments.
    

Intervention name(s): GSK2190915 100mg milled tablet; [14C] radiolabelled GSK2190915 solution; GSK2190915 100mg milled tablet administered to the proximal small bowel.; GSK2190915 100mg milled tablet administered to the distal small bowel.; GSK2190915 100mg enteric-coated tablet.
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Taken orally; Microtracer solution; Ground half of a 200mg tablet. Administered via Enterion capsule.; Ground half of a 200mg tablet. Administered via Enterion capsule.; Taken orally
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: ADME; IV radiolabelled; pharmacokinetics