Clinical trial NCT00599612: To Assess the Excretion Balance and Pharmacokinetics of a Single Oral Dose of [14C]GW856553 in Healthy Adult Males
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: GW856553,
radiolabel
ADME,
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-01-24
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of the total radioactive dose administered over time
timeFrame: Up to 10 days
Secondary outcomes:
measure: Area under the concentration time curve (AUC) from time zero to infinity (AUC[0-inf]) of total drug
timeFrame: 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
measure: Maximum plasma concentration(Cmax) of total drug
timeFrame: 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
measure: AUC from zero to the time of the last measurable concentration (AUC[0-t]) of total drug
timeFrame: 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
measure: First time of occurrence of maximum observed concentration (Tmax) of total drug
timeFrame: 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
measure: Terminal plasma half-life (t1/2) of total drug
timeFrame: 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
measure: AUC(0-inf) of GW856553
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: AUC(0-inf) of GSK198602
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: Cmax of GW856553
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: Cmax of GSK198602
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: AUC(0-t) of GW856553
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: AUC(0-t) of GSK198602
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: Tmax of GW856553
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: Tmax of GSK198602
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: T1/2 of GW856553
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: T1/2 of GSK198602
timeFrame: Pre-dose and 1, 4, 12 hours post-dose
measure: Number of subjects with Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 15 days
measure: Number of subjects with abnormal ECG findings
timeFrame: Up to 15 days
measure: Number of subjects with abnormal blood pressure values
timeFrame: Up to 15 days
measure: Number of subjects with abnormal heart rate values
timeFrame: Up to 15 days
measure: Number of subjects with abnormal clinical chemistry parameters
timeFrame: Up to 15 days
measure: Number of subjects with abnormal clinical hematology parameters
timeFrame: Up to 15 days
measure: Number of subjects with abnormal urine analysis parameters
timeFrame: Up to 15 days
measure: Number of subjects with abnormal liver function tests
timeFrame: Up to 15 days
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: