A Study to Determine the Excretion Balance and Pharmacokinetics of 14C-GSK573719
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Drug: Treatment Period 2 - Oral dose of GSK573719Drug: Treatment Period 1 - IV dose of GSK573719
- Registration Number
- NCT01362257
- Lead Sponsor
- GlaxoSmithKline
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 14C-GSK573719 Oral Solution Treatment Period 2 - Oral dose of GSK573719 single dose of 1000µg 14C-GSK573719 IV Solution Treatment Period 1 - IV dose of GSK573719 single dose of 65µg
- Primary Outcome Measures
Name Time Method AUC(0-∞), AUC(0-t), Cmax, tmax, λz and t1/2 of total drug-related material (radioactivity) and GSK573719 in plasma following intravenous and oral dosing up to 8 days post-dose AUC(0-∞) = area under concentration time curve from time zero extrapolated to infinite time. AUC(0-t) = Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments. Cmax = Maximum observed concentration. tmax = Time of occurrence of Cmax. λz = Terminal phase rate constant. t1/2 = Terminal phase half life.
Urinary and faecal cumulative excretion as a percentage of the total radioactive dose administered over time up to 14 days post dose
- Secondary Outcome Measures
Name Time Method Characterisation and quantification of metabolites in plasma, urine, duodenal bile and faecal homogenates to be documented and performed by DMPK, GSK and the results will be reported in a separate report up to 14 days post dose Oral F (absolute bioavailability) up to 8 days post dose AUClast for oral dose, volume and clearance for intravenous dose up to 8 days post dose AUC = Area under concentration-time curve
Blood: plasma ratio of total drug related material (radioactivity) up to 8 days post dose Spontaneous AE reporting, 12-lead ECG, vital signs and safety laboratory tests up to 14 days post dose
Trial Locations
- Locations (1)
GSK Investigational Site
🇳🇱Zuidlaren, Netherlands