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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00599612
First received: January 11, 2008
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

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 mg oral dose of GW856553 containing 50 microCi of [14C] GW856553. Urine and faecal samples will be collected until 216 h after dosing but subjects may be discharged after 168 h if 90% of the dose is recovered and/or <1% of the dose is excreted in a 24 h 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 characterise and quantify metabolites in these matrices. Safety will be assessed by adverse event monitoring, vital signs, ECG and clinical laboratory tests.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GW856553
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Urinary and fecal cumulative excretion as a percentage of the total radioactive dose administered over time. Collection, for approximately 10 days (or longer) of plasma, urine and fecal samples for assessment of parent and metabolites. [ Time Frame: approximately 10 days ]

Secondary Outcome Measures:
  • Clinical Safety data. PK parameters of GW856553 and drug-related material (radioactivity) in plasma urine and faeces following oral dosing. Samples are collected for approximately 10 days (or longer) following oral dosing. [ Time Frame: approximately 10 days ]
  • AUC(0-inf), Cmax, AUC(0-t), tmax and t½ of total drug-related material (radioactivity) in plasma following oral dosing.
  • AUC(0-inf), Cmax, AUC(0-t), tmax, t½ of GW856553 and its major metabolite GSK198602 in plasma following oral dosing.
  • Adverse events, ECG, vital signs and clinical laboratory tests (including LFTs).
  • Characterisation and quantification of metabolites in plasma, urine and faecal homogenates will be performed under a separate protocol by Drug Metabolism and Pharmacokinetics (DMPK), GSK and results will be reported in a separate report.

Enrollment: 6
Study Start Date: January 2008
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GW856553
    Other Name: GW856553
  Eligibility

Ages Eligible for Study:   30 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male aged between 30 and 60 years inclusive, at the time of screening.
  • Body weight >/ 50 kg (110 lbs).
  • A body mass index (BMI) within the range of 18.5 to 29.9 kg/m2 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.
  • QTc(b) > 450msecs
  • 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 (284mL) 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, GammaGT 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00599612

Locations
United Kingdom
GSK Investigational Site
Edinburgh, United Kingdom, EH33 2NE
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00599612     History of Changes
Other Study ID Numbers: 107806
Study First Received: January 11, 2008
Last Updated: January 19, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
GW856553,
radiolabel
ADME,

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive

ClinicalTrials.gov processed this record on September 22, 2014