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Pulmonary Disease, Chronic ObstructivePhase 1NCT01286831

A Single Dose Study to Determine the Excretion, Balance and Metabolic Disposition of Radiolabelled GW642444.

A Phase 1 study testing [14C]GW642444 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to characterise the metabolic disposition of radiolabelled GW642444 when administered orally. Read more about this study

Who is it for?
Ages 30 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
[14C]GW642444
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteNetherlands
Study dates
18 May 2010to 9 Jul 2010
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
  • Body Mass Index (BMI) within the range 18.5-29.0 kg/m2 (inclusive).
  • 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]
  • AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • 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:
  • Sinus bradycardia <45bpm
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  • 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)
  • No significant abnormality on the Holter ECG at screening.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Who cannot join

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • 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.
  • Females.
  • The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • 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).
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  • History of or current spastic/ hyperactive colon.
  • Subjects who do not have regular defecation patterns (regular defined as passing faeces at least once every two days).
  • 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.
  • 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.
  • 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.
  • 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]).
  • 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).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • 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.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • The subject has tested positive for HIV antibodies.
  • A positive urine drug screen at screening, on admission to the unit, or when randomly tested during the study.
  • Positive alcohol urine test at screening or on admission to the Unit.
  • Positive urine cotinine test at screening.
  • Consumption of seville oranges, pomelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • GSK Investigational Site

    Zuidlaren, 9471 GP

Other trials in Netherlands

About this study

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

The purpose of this study is to characterise the metabolic disposition of radiolabelled GW642444 when administered orally.

Read the detailed description

This will be a single-centre, open-label, single-dose study to characterise the metabolic disposition of oral [14C]GW642444. Six healthy male subjects will be enrolled to ensure at least four fully evaluable subjects. Each subject will receive a single 200μg oral dose of GW642444 containing 2 μCi (0.074MBq) of [14C]GW642444. Whilst subjects are inhouse, blood, urine and faecal samples will be collected for a minimum of 168 hours after dosing (7 days) or for up to 240 hours (10 days) depending on amounts of radioactivity still being excreted after Day 5. Faecal sample collection may continue at home for up to 14 days. Bile samples will be collected using Entero-Test string sampling of duodenal bile. Plasma will be prepared from blood at various sample times after dosing to measure parent drug and total radiolabelled drug-related material. Urine and faeces aliquots will be taken to measure total radiolabelled drug-related material. Samples of urine, faeces, plasma and bile will be transferred into a separate study to characterise and, where feasible, quantify metabolites in these matrices. Safety and tolerability will be assessed by blood pressure, heart rate, 12- lead electrocardiogram (ECG), clinical laboratory safety tests, and collection of adverse events (AEs).

Being tested
[14C]GW642444
Keywords
Accelerator Mass Spectrometry (AMS), Beta-2 agonist, Absorption, Distribution, Metabolism and Excretion (ADME), Radiolabel
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [14C]GW642444Drug

    Single 200μg dose of [14C]GW642444 given on Day 1.

Study groups in NCT01286831
Study groupRoleWhat they receive
[14C]GW642444ExperimentalSingle 200μg dose of [14C]GW642444 given on Day 1.
Receives: Drug: [14C]GW642444

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUC(0-∞), AUC(0-t), Cmax, tmax, λz and t1/2 of total drug-related material (radioactivity) in plasma following oral dosing.

    Measured: Two months from first dose.

  2. AUC(0-t), Cmax and tmax of GW642444 following oral dosing.

    Measured: Two months from first dose.

  3. Urinary and faecal cumulative excretion as a percentage of the total radioactive dose administered over time.

    Measured: Two months from first dose.

Secondary outcomes (2)

  1. Characterisation of metabolites in plasma, urine, duodenal bile and faecal homogenates.

    Measured: One year from last subject last visit

  2. Vital signs, 12-lead ECG, Clinical laboratory tests, AEs.

    Measured: Two weeks from first dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2011 (estimated)
  2. Study start18 May 2010
  3. Primary completion9 Jul 2010
  4. Study completion9 Jul 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01286831
Sponsor's protocol ID
106181
Status last verified
Jun 2017
First submitted
6 May 2010
Last updated
20 Jun 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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 beta(2)-adrenoceptor agonist for inhalation use in humans. Drug Metab Dispos. 2013 Jan;41(1):89-100. doi: 10.1124/dmd.112.048603. Epub 2012 Oct 4.

    PubMed 23043183

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [14C]GW642444 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC(0-∞), AUC(0-t), Cmax, tmax, λz and t1/2 of total drug-related material (radioactivity) in plasma following oral dosing. (time frame: Two months from first dose.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01286831, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.

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