Last updated: 11/07/2018 04:18:11
A study to determine the excretion balance and pharmacokinetics of 14C-GSK573719
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: An open-label, two period study to determine the excretion balance and pharmacokinetics of 14C-GSK573719, administered as single dose of an oral solution and an intravenous infusion, to healthy male adults
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
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
Timeframe: up to 8 days post-dose
Urinary and faecal cumulative excretion as a percentage of the total radioactive dose administered over time
Timeframe: up to 14 days post dose
Secondary outcomes:
Oral F (absolute bioavailability)
Timeframe: up to 8 days post dose
AUClast for oral dose, volume and clearance for intravenous dose
Timeframe: up to 8 days post dose
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
Timeframe: up to 14 days post dose
Blood: plasma ratio of total drug related material (radioactivity)
Timeframe: up to 8 days post dose
Spontaneous AE reporting, 12-lead ECG, vital signs and safety laboratory tests
Timeframe: up to 14 days post dose
Interventions:
Drug: Treatment Period 1 - IV dose of GSK573719
Drug: Treatment Period 2 - Oral dose of GSK573719
Enrollment:
6
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Kelleher D, Hughes S, Mehta R, Tombs L, Kelly K, Church A. Absorption, distribution, metabolism, and elimination (ADME) of umeclidinium (UMEC) in healthy adults. Eur Respir J. 2012;40(Suppl. 56):384s.
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
umeclidinium bromide
Collaborators
Not applicable
Study date(s)
April 2011 to June 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
30 - 55 years
Accepts healthy volunteers
Yes
- Inclusion:
Inclusion and exclusion criteria
Inclusion criteria:
- Inclusion: AST (Aspartate aminotransferase), ALT (Alanine aminotransferase), alkaline phosphatase and bilirubin ≤ 1.5xULN (Upper limit of normal) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) Healthy, non-smoking male subjects, 30-55 years old inclusive Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1 Body Mass Index (BMI) within the range 18.5-29.0 kg/m2 (inclusive) Capable of giving written informed consent Average QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block Available to complete the study A history of regular bowel movements Exclusion: A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening A positive test for HIV (Human Immunodeficiency Virus) antibody Current or chronic history of liver disease, or known hepatic or biliary abnormalities Any clinically relevant abnormality identified on the screening medical assessment laboratory examination or 12-lead ECG (Electrocardiogram) Subjects with a positive urine test for drugs of abuse or alcohol at screening or prior to study medication administration Positive urine cotinine at screening History of regular alcohol consumption within 6 months of the study Treatment with an investigational drug within 60 days or 5 half-lives preceding the first dose of study medication Subjects who have had exposure to more than four new chemical entities within 12 months prior to the first dosing period Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 5 half-lives prior to the first dose of study medication Subjects who have received prescription medication within 14 days prior to the first dose of study drug. Subjects may still be entered into the study, if the prescription medication will not interfere with study procedures or compromise safety Donation of blood in excess of 500mL within 56 days prior to the first dose of study medication Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months Subjects who have received a total body radiation dose of greater than 5.0 mSv or exposure to significant radiation in the 12 months prior to this study Previous history of active gastric or duodenal ulcer within 6 months prior to the first dose of study medication Any history of bleeding diathesis A pre-existing condition(s) interfering with normal gastrointestinal (GI) anatomy or motility or other GI dysfunction which may interfere with the absorption, distribution, metabolism or elimination of the study drug Surgical procedures on digestive tract An occupation which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays within the past 12 months History of anaphylaxis or anaphylactoid reactions, severe allergic responses to drugs History of sensitivity to any of the study medications Unwillingness or inability to follow the procedures outlined in the protocol Subject is mentally or legally incapacitated
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2011-22-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 112014 can be found on the GSK Clinical Study Register.
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