To Assess the Excretion Balance and Pharmacokinetics of a Single Oral Dose of [14C]GW856553 in Healthy Adult Males

An Open Label Study to Determine the Safety, Tolerability, Excretion Balance and Pharmacokinetics of [14C]GW856553, Administered as a Single Dose of an Oral Solution to Healthy Adult Male Subjects

This will be an open label study conducted at one site. Six healthy male subjects will be enrolled to ensure at least four fully evaluable subjects. Each subject will receive a single 10 milligram (mg) oral dose of GW856553 containing 50 microCi (µCi) of [14C] GW856553. Urine and fecal samples will be collected until 216 hour after dosing but subjects may be discharged after 168 hour if 90% of the dose is recovered and/or <1% of the dose is excreted in a 24 hour period. Blood and plasma will be collected at various sample times after dosing to measure parent drug and total drug-related material. Samples of urine, faeces and plasma will be transferred into a separate study to characterize and quantify metabolites in these matrices. Safety will be assessed by adverse event monitoring, vital signs, electrocardiogram (ECG) and clinical laboratory tests.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GW856553

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH33 2NE
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male aged between 30 and 60 years inclusive, at the time of screening.
• Body weight >/ 50 kilogram (kg).
• A body mass index (BMI) within the range of 18.5 to 29.9 kg/ meter square (m^2) inclusive.
• Signed and dated written informed consent prior to admission to the study.
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

• Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG (12-lead).
• Significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
• QT interval corrected by Bazett's Formula (QTcB) > 450 milliseconds (msecs)
• A definite or suspected personal or family history of adverse reactions or hypersensitivity to the trial drug or to drugs with a similar chemical structure.
• History of regular alcohol consumption exceeding an average weekly intake of > 21 units (or an average daily intake of greater than 3 units). One unit is equivalent to a half-pint [284 milliliter (mL)] of beer/lager; 25mL measure of spirits or 125mL of wine).
• Subjects with a history or presence of gastro-intestinal or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Subjects who have consumed grapefruit or grapefruit juice within seven days of the first study day.
• Subjects who have had exposure to more than three new chemical entities within 12 months prior to the first dosing period.
• Subjects who have participated in a trial with a different new chemical entity within 90 days prior to the start of this study.
• If participation in the study will result in the volunteer having donated more than 400mL of blood in the previous 56 days.
• Subjects who have received a total body radiation dose of greater than 5.0 mSv (upper limit of WHO category II) or exposure to significant radiation (e.g. serial X-ray or CT scans, barium meal etc) in the 12 months prior to this study.
• History of elevated blood pressure or blood pressure persistently >140/90 mmHg at screening.
• An unwillingness to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, sub dermal implants or a tubal ligation if the women could become pregnant from the time of the first dose of the study medication until completion of the follow-up procedures.
• Lack of suitability for participation in this study, for any reason, in the opinion of the investigator.
• Any condition that could interfere with the accurate assessment and recovery of 14C.
• Prescribed or over-the-counter medication within 5 days (or 5 half lives, whichever is longer) prior to the first dosing day, unless the investigator confirms that it will not introduce additional risk or interfere with the study procedures or outcome.
• Liver function tests (ALT, AST, ALP, Gamma GT and bilirubin) > upper limit of normal (ULN) at screening
• Positive urine drug screen
• Positive HIV, Hepatitis B or C result at screening.
• History of use of tobacco- or nicotine-containing products within 6 months of screening or a positive urine cotinine screen (urine cotinine > 250ng/ml).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy male volunteers; Six healthy male volunteers aged between 30-60 years old will be recruited for this study,	Drug: GW856553; A dose of 10mg GW856553 containing 50µCi of [14C]GW856553 will be delivered as 100mL of a 0.1mg/mL GW856553/0.5 µCi/mL oral solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of the total radioactive dose administered over time	The urinary and fecal cumulative excretion will be analyzed.	Up to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration time curve (AUC) from time zero to infinity (AUC[0-inf]) of total drug	Blood samples will be collected at specific time points for calculating AUC (0-inf)	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose
Maximum plasma concentration(Cmax) of total drug	Blood samples will be collected at specific time points for calculating Cmax	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose
AUC from zero to the time of the last measurable concentration (AUC[0-t]) of total drug	Blood samples will be collected at specific time points for calculating AUC(0-t)	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose
First time of occurrence of maximum observed concentration (Tmax) of total drug	Blood samples will be collected at specific time points for calculating Tmax	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose
Terminal plasma half-life (t1/2) of total drug	Blood samples will be collected at specific time points for calculating T1/2	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose
AUC(0-inf) of GW856553	Blood samples will be collected at specific time points for calculating AUC(0-inf)	Pre-dose and 1, 4, 12 hours post-dose
AUC(0-inf) of GSK198602	Blood samples for metabolite analysis will be collected at specific time points for calculating AUC(0-inf)	Pre-dose and 1, 4, 12 hours post-dose
Cmax of GW856553	Blood samples will be collected at specific time points for calculating Cmax	Pre-dose and 1, 4, 12 hours post-dose
Cmax of GSK198602	Blood samples for metabolite analysis will be collected at specific time points for calculating Cmax	Pre-dose and 1, 4, 12 hours post-dose
AUC(0-t) of GW856553	Blood samples will be collected at specific time points for calculating AUC(0-t)	Pre-dose and 1, 4, 12 hours post-dose
AUC(0-t) of GSK198602	Blood samples for metabolite analysis will be collected at specific time points for calculating AUC(0-t)	Pre-dose and 1, 4, 12 hours post-dose
Tmax of GW856553	Blood samples will be collected at specific time points for calculating Tmax	Pre-dose and 1, 4, 12 hours post-dose
Tmax of GSK198602	Blood samples for metabolite analysis will be collected at specific time points for calculating Tmax	Pre-dose and 1, 4, 12 hours post-dose
T1/2 of GW856553	Blood samples will be collected at specific time points for calculating T1/2	Pre-dose and 1, 4, 12 hours post-dose
T1/2 of GSK198602	Blood samples for metabolite analysis will be collected at specific time points for calculating T1/2	Pre-dose and 1, 4, 12 hours post-dose
Number of subjects with Adverse events (AEs) and serious adverse events (SAEs)	An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.	Up to 15 days
Number of subjects with abnormal ECG findings	Full 12-lead ECGs will be recorded using an ECG machine	Up to 15 days
Number of subjects with abnormal blood pressure values	Systolic and diastolic blood pressure values will be measured in a supine position having rested in this position for at least 10 minutes before each reading.	Up to 15 days
Number of subjects with abnormal heart rate values	Heart rate values will be measured in a supine position having rested in this position for at least 10 minutes before each reading.	Up to 15 days
Number of subjects with abnormal clinical chemistry parameters	Samples for clinical chemistry tests will be collected as a measure of safety	Up to 15 days
Number of subjects with abnormal clinical hematology parameters	Samples for clinical hematology tests will be collected as a measure of safety	Up to 15 days
Number of subjects with abnormal urine analysis parameters	Urine samples for urine analysis tests will be collected as a measure of safety	Up to 15 days
Number of subjects with abnormal liver function tests	Samples for liver function tests will be collected as a measure of safety	Up to 15 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2008
• Primary Completion (Actual): February 18, 2008
• Study Completion (Actual): February 18, 2008

Study Registration Dates

• First Submitted: January 11, 2008
• First Submitted That Met QC Criteria: January 11, 2008
• First Posted (Estimate): January 24, 2008

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: radiolabel; GW856553,; ADME,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 107806