A Study to Determine the Excretion Balance and Pharmacokinetics of 14C-GSK573719
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 1

Summary: 
      This will be a two-period, open-label study conducted at a single site. Six healthy male
      subjects will participate in the study to ensure at least four fully evaluable subjects. Each
      subject will receive a single 1000 μg (microgram) oral dose containing 50 μCi (Micro Curie)
      of [14C]-GSK573719 and a 65 μg intravenous infusion containing 7.1 μCi of [14C]-GSK573719.
      Whilst subjects are in-house, urine and faecal samples will be collected for a minimum of 168
      hours (7 days) after dosing or for up to 240 hours (10 days) depending on the amounts of
      radioactivity still being excreted after Day 5. Faecal sample collection may continue at home
      for up to 14 days. Bile samples will be collected using Entero-Test string sampling of
      duodenal bile. Whole blood and plasma samples will be collected at various sample times after
      dosing to measure parent drug (plasma only) and total radiolabelled drug related material
      (blood and plasma). Urine and faeces aliquots will be taken to measure total radiolabelled
      drug-related material. Samples of urine, faeces and plasma will be transferred into a
      separate study to characterize and, where possible, quantify metabolites in these matrices.
    

Detailed description: 
      This will be a single-centre, open-label, two period study in healthy male subjects. Each
      subject will participate in two separate dosing periods. In the first dosing period, each
      subject will receive a 65 μg single dose of intravenous infusion containing 7.1 μCi of
      [14C]-GSK573719 administered over 30 minutes. In the second dosing period, each subject will
      receive a single 1000 μg oral dose containing 50 μCi of [14C]-GSK573719. Each study period
      will involve an admission to the CRO (clinical research organisation) unit of between 7 and
      10 days. The two dosing periods will be separated by a wash-out of at least 28 days between
      doses. Screening will occur within 30 days prior to the first dosing period. Each subject
      will be admitted to the clinical unit on the afternoon of Day -1. Whilst subjects are
      in-house, blood, urine and faecal samples will be collected for a minimum of 168 hours (7
      days) after dosing or for up to 240 hours (10 days), depending on amounts of radioactivity
      still being excreted after day 5. Liquid scintillation counts (LSC) will be performed daily
      on the 24-hour urine pools and 24-hour faeces homogenates after Day 5 to measure total
      radioactivity concentrations. If less than 1% of the dose is excreted in each 24 hour period
      on Day 6 and Day 7 for a given subject, that subject will be discharged on Day 8, after the
      results of the LSC counts are available, and no further samples will be collected. If
      excretion is higher than 1%, or if the results are inconclusive, the subject will remain
      in-house, and urine and faecal collections will continue at 24 hour intervals, until
      excretion is less than 1% on Day 8, 9 or 10; again subjects will be discharged after the
      results of the LSC counts are available. On the morning of Day 11, all remaining subjects
      will be discharged from the clinic and subjects will be notified by phone as to whether they
      need to continue faecal collection at home. In the event that excretion is still higher than
      1% upon discharge on Day 11, subjects will continue to collect faecal samples only, at home,
      at 24 hour intervals up to and including Day 14. Samples collected at home will be returned
      to the clinic every 2-3 days. The Entero-Test will be used in Treatment Period 1 only (IV
      dosing). The Entero-Test will be inserted at approximately 3.5 hours pre-dose while subjects
      are in a fasted state and removed at approximately 2.5 hours post-dose on day 1. At
      approximately 0.5 hours post-dose (i.e. two hours prior to string withdrawal) a food cue will
      be used to stimulate gall bladder emptying. Safety data collected will include spontaneous AE
      (adverse event) reporting, 12-lead ECG (electrocardiogram), vital signs, nursing/physician
      observation and safety laboratory tests. Subjects will complete follow up assessments within
      8-12 days of their last dose (this may happen on the day of discharge from the unit). Final
      follow up contact will then be via telephone call to the subjects 2 to 3 days after final
      sample collection. The duration of the study will be approximately 11 to 12 weeks for each
      subject.
    

Intervention name(s): Treatment Period 1 - IV dose of GSK573719; Treatment Period 2 - Oral dose of GSK573719
Intervention type(s): Drug; Drug
Intervention description(s): single dose of 65µg; single dose of 1000µg
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment