A Study to Determine the Excretion Balance and Pharmacokinetics of 14C-GSK573719

NCT01362257 | Completed Phase 1

• 1 other identifier: 112014
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  up to 8 days post-dose

• Urinary and faecal cumulative excretion as a percentage of the total radioactive dose administered over time

  up to 14 days post dose

Secondary Outcomes (5)

• 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

• 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

• 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

Study Arms (2)

14C-GSK573719 Oral Solution

EXPERIMENTAL

single dose of 1000µg

Drug: Treatment Period 2 - Oral dose of GSK573719

14C-GSK573719 IV Solution

EXPERIMENTAL

single dose of 65µg

Drug: Treatment Period 1 - IV dose of GSK573719

Interventions

Treatment Period 1 - IV dose of GSK573719 DRUG

single dose of 65µg

14C-GSK573719 IV Solution

Treatment Period 2 - Oral dose of GSK573719 DRUG

single dose of 1000µg

14C-GSK573719 Oral Solution

Eligibility Criteria

• Age: 30 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Zuidlaren, 9471 GP, Netherlands

Location

Related Links

• Results for study 112014 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2011
• First Posted: May 30, 2011
• Study Start: April 29, 2011
• Primary Completion: June 22, 2011
• Study Completion: June 22, 2011
• Last Updated: June 27, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)