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To Assess the Excretion Balance and Pharmacokinetics of a Single Oral Dose of [14C]SB-681323 in Healthy Adult Males

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00564746
First received: November 26, 2007
Last updated: October 2, 2014
Last verified: January 2012
  Purpose

SB-681323 is a p38 MAP kinase inhibitor and is currently under development by GlaxoSmithKline. 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 10mg/ 50 µCurie oral dose of [14C]SB-681323. 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 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: A single 10mg (50 μCi) oral dose of [14C]SB-681323
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open Label Study to Determine the Excretion Balance and Pharmacokinetics of [14C]SB-681323, 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 faecal cumulative excretion as a percentage of the total radioactive dose administered over time. [ Time Frame: 168 Hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • AUC(0-8), Cmax, AUC(0-t), tmax and t½ of total radioactivity and SB8681323 in plasma following oral dosing.- Blood:Plasma ratio of total radioactivity.- AEs, ECG, vital signs and clinical laboratory tests (including LFTs). [ Time Frame: 216 Hours ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: September 2007
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 6 subjects in a single cohort Drug: A single 10mg (50 μCi) oral dose of [14C]SB-681323
This intervention will be dosed IV.

Detailed Description:

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 10mg/ 50 µCurie oral dose of [14C]SB-681323. 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 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.

  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 Xray 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, ?GT and bilirubin) > upper limit of normal (ULN) at screening
  • Creatinine phosphokinase (CPK) > 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: NCT00564746

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

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00564746     History of Changes
Other Study ID Numbers: SB681323/011
Study First Received: November 26, 2007
Last Updated: October 2, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Ethics Committee

Keywords provided by GlaxoSmithKline:
radiolabel
SB-681323,
ADME,

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

ClinicalTrials.gov processed this record on November 20, 2014