Last updated: 11/07/2018 01:22:33
A single dose study to determine the excretion, balance and metabolic disposition of radiolabelled GW642444.
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: An open-label, single-arm study to determine the excretionbalance and metabolic disposition of [14C]GW642444administered as a single dose of an oral solution to healthy malevolunteers
Trial description: The purpose of this study is to characterise the metabolic disposition of radiolabelled GW642444 when administered orally.
Primary purpose:
Other
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
AUC(0-∞), AUC(0-t), Cmax, tmax, λz and t1/2 of total drug-related material (radioactivity) in plasma following oral dosing.
Timeframe: Two months from first dose.
AUC(0-t), Cmax and tmax of GW642444 following oral dosing.
Timeframe: Two months from first dose.
Urinary and faecal cumulative excretion as a percentage of the total radioactive dose administered over time.
Timeframe: Two months from first dose.
Secondary outcomes:
Characterisation of metabolites in plasma, urine, duodenal bile and faecal homogenates.
Timeframe: One year from last subject last visit
Vital signs, 12-lead ECG, Clinical laboratory tests, AEs.
Timeframe: Two weeks from first dose.
Interventions:
Enrollment:
6
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Harrell AW, Siederer SK, Bal J, Patel NH, Young GC, Felgate CC, Pearce SJ, Roberts AD, Beaumont C, Emmons AJ, Pereira AI, Kempsford RD. Metabolism and disposition of vilanterol, a long-acting beta2 adrenoreceptor agonist, for inhalation use in human. Drug Metab Dispos. 2013;41(1):89-100.
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
vilanterol
Collaborators
Not applicable
Study date(s)
May 2010 to July 2010
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
30 - 55 years
Accepts healthy volunteers
Yes
- 1. Healthy male aged between 30 and 55 years inclusive, at the time of signing the
- informed consent.
- A subject will not be eligible for inclusion in this study if any of the following criteria
- apply:
Inclusion and exclusion criteria
Inclusion criteria:
- Sinus bradycardia <45bpm
- Sinus tachycardia ≥110bpm
- Multifocal atrial tachycardia (wandering atrial pacemaker with rate >100bpm)
- PR interval >240msec
- Evidence of Mobitz II second degree or third degree atrioventricular (AV) block.
- Pathological Q waves (defined as wide [>0.04 seconds] and deep [>0.4mV (4mm with 10mm/mV setting)] or >25% of the height of the corresponding R wave, providing the R wave was >0.5mV [5mm with 10mm/mV setting], appearing in at least two contiguous leads.
- Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal premature ventricular complexes.
- QTcF ≥450msec or uncorrected QT >600msec or an ECG that is unsuitable for QT measurements (e.g., poor defined termination of the T wave) Note: QTcF ≥450msec or uncorrected QT >600msec should be confirmed by three readings at least 5 minutes apart.
- ST-T wave abnormalities (excluding non-specific ST-T wave abnormalities)
- Right or left complete bundle branch block
- Clinically significant conduction abnormalities (e.g., left bundle branch block, Wolff-Parkinson-White syndrome)
- Clinically significant arrhythmias (e.g., atrial fibrillation with rapid ventricular response, ventricular tachycardia) 6. No significant abnormality on the Holter ECG at screening. 7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
1. Healthy male aged between 30 and 55 years inclusive, at the time of signing the informed consent. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population, which are deemed to be clinically relevant, should always be excluded from enrollment. 2. Body Mass Index (BMI) within the range 18.5-29.0 kg/m2 (inclusive). 3. Subjects who are current non-smokers, who have not used any tobacco products in the 12 month period preceding the screening visit, and have a pack history of ≤ 5 pack years. [number of pack years = (number of cigarettes per day/20) x number of years smoked] 4. AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 5. No significant abnormality on 12-lead ECG at screening. Selected specific ECG findings that are considered to be significant and will exclude the subject from study participation include, but are not limited to, the following:
Exclusion criteria:
- A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. As a result of medical interview, physical examination or screening investigations, the principal investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 90 mmHg. 2. Females. 3. The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness. 4. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 5. Surgical procedures on digestive tract including corrective surgery for appendicitis (in the 3 months prior to screening) or diverticulitis, cholecystectomy (gallbladder removal), and/or cholelithotomy (gallstone removal). 6. History of or current spastic/ hyperactive colon. 7. Subjects who do not have regular defecation patterns (regular defined as passing faeces at least once every two days). 8. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 9. Any adverse reaction including immediate or delayed hypersensitivity to any β2-agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of the GW642444formulation for oral administration. 10. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. 11. History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males). One unit is equivalent to a 285mL glass of full strength beer or 425mL schooner of light beer or 1 (30mL) measure of spirits or 1 glass (100mL) of wine (NHMRC Guidelines [NHMRC, 2001]). 12. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 60 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 13. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 14. Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A subjects previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination / carryover into the current study. 15. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 16. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 17. The subject has tested positive for HIV antibodies. 18. A positive urine drug screen at screening, on admission to the unit, or when randomly tested during the study. 19. Positive alcohol urine test at screening or on admission to the Unit. 20. Positive urine cotinine test at screening. 21. Consumption of seville oranges, pomelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication. 22. Unwillingness or inability to follow the procedures outlined in the protocol. 23. Subject is mentally or legally incapacitated.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2010-09-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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