Pulmonary Disease, Chronic ObstructivePhase 1NCT01571999
Study to Assess the Safety and PK of GSK573719 and GSK573719/GW642444(VI) Combination in Healthy Subjects and Subjects With Severe Renal Impairment
A Phase 1 study testing Inhaled GSK573719 and Inhaled GSK573719/vilanterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 2 sites in 2 countries.
Trial summary
This study will assess the safety and pharmacokinetics of inhaled GSK573719 and GSK573719/vilanterol combination in healthy subjects and in subjects with severe renal impairment. The results of the study will provide guidance on the use of this product in subjects with severe renal impairment. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Inhaled GSK573719 and Inhaled GSK573719/vilanterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 29 Mar 2012to 22 Jun 2012
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or, child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol for an appropriate period of time prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until follow-up.
- Body weight greater than or equal to 45 kg and body mass index (BMI) within the range 18 - 33 kg/m2 (inclusive)
- Single QTcF less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.
- Healthy Subjects:
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- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN)
- Creatinine clearance greater than 80mL/min calculated by the Cockcroft-Gault equation using serum creatinine
- Renally Impaired subjects:
- ALT less than 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN
- Creatinine clearance less than 30mL/min calculated by the Cockcroft-Gault equation using serum creatinine.
- Subjects with renal insufficiency must have stable renal function defined as less than or equal to a 25% difference in creatinine clearance assessed on two occasions. Renal function will be based on estimated creatinine clearance (CLcr) calculated by the Cockcroft-Gault equation using serum creatinine obtained on two occasions separated by at least 4 weeks within the last 3 months
Who cannot join
- Suffered a lower respiratory tract infection in the 4 weeks before the screening visit
- A supine mean heart rate outside the range 40-90 beats per minute (BPM) at screening
- A positive pre-study drug/alcohol screen
- A positive test for HIV antibody
- Current or chronic history of liver disease, including documented cirrhosis or a history consistent with a diagnosis of cirrhosis, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- 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: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
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- Exposure to more than four new chemical entities within 12 months prior to the first dosing day
- Use of nephrotoxic medications 4 weeks before dosing
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Lactating females
- The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness
- Unwillingness or inability to follow the procedures outlined in the protocol
- Subject is mentally or legally incapacitated
- Subjects with smoking history of greater than 10 cigarettes per day or regular use of tobacco- or nicotine-containing products, within 6 months prior to screening
- 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.
- Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
- Healthy Subjects:
- Subjects with any predisposing condition that might interfere with the absorption, distribution, metabolism or excretion of drugs or any previous gastrointestinal (GI) surgery which the investigator considers sufficiently significant to interfere with the conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
- Urinary tract or bladder infection within 4 weeks of the first scheduled administration of study drug.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males or greater than 14 units for females.
- Unable to refrain from the 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.
- Renally Impaired Subjects:
- Life expectancy less than 3 months
- Hemoglobin less than 8.5 g/dL (for sites in Hungary), or hemoglobin less than 11.0g/dL (for sites in the Czech Republic)
- Subjects on hemodialysis treatment
- Subjects who, within the past six months, have had a history of significant drug abuse or alcohol abuse
- Subjects who need to take any concomitant medication, either prescribed or overthe- counter, which may in the opinion of the Investigator, interfere in any way with the study procedure or be a safety concern. In particular subjects taking medications that significantly inhibit P450 CYP3A4 (e.g. ketaconazole) must not be included in this study
- If in the opinion of an examining physician an unstable cardiovascular, pulmonary or hepatic condition is present, or any other medical condition which the investigator considers sufficiently serious to interfere with the conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Single-blind, Non-randomized Pharmacokinetic and Safety Study of Single Dose of GSK573719 and GSK573719 + GW642444 Combination in Healthy Subjects and in Subjects With Severe Renal Impairment
This study will assess the safety and pharmacokinetics of inhaled GSK573719 and GSK573719/vilanterol combination in healthy subjects and in subjects with severe renal impairment. The results of the study will provide guidance on the use of this product in subjects with severe renal impairment.
Read the detailed description
GSK573719 monotherapy and GSK573719/vilanterol combination are currently under development for the treatment of COPD. This study will assess the pharmacokinetics and safety of inhaled GSK573719 and GSK573719/vilanterol (VI) in healthy subjects and in subjects with severe renal impairment. Nine subjects with severe renal impairment (as defined by a Clcr<30mL/min) will be recruited along with healthy control subjects (as defined by a Clcr>80mL/min matched to the severe renal impairment subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years)). The results from this study will provide guidance on the use of GSK573719 and GSK573719/VI in severe renally impaired patients.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Inhaled GSK573719, Inhaled GSK573719/vilanterol
- Keywords
- pharmacokinetics, GW642444, GSK573719, vilanterol, renal impairment, safety, COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled GSK573719Drug
All subjects will receive a single dose of GSK573719 (125mcg) in treatment period 1
Inhaled GSK573719/vilanterolDrug
All subjects will receive a single dose of GSK573719 (125mcg)/vilanterol (25mcg) in treatment period 2
| Study group | Role | What they receive |
|---|---|---|
| Severe renally impaired subjects | Experimental | Approximately 9 subjects will complete each treatment arm Receives: Drug: Inhaled GSK573719; Drug: Inhaled GSK573719/vilanterol |
| Matched healthy volunteers | Experimental | Matched to the severe renal impairment subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years). Approximately 9 subjects will complete each treatment arm Receives: Drug: Inhaled GSK573719; Drug: Inhaled GSK573719/vilanterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
GSK573719 and vilanterol plasma pharmacokinetic parameters
Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2
Measured: Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 2hrs, 4hrs, 8hrs, 12hrs, 16hrs, 24hrs
Secondary outcomes (5)
GSK573719 urine pharmacokinetic parameters
Measured: Treatment Period 1 and 2: 0-4hrs, 4-8hrs, 8-12hrs, 12-24hrs
Vital Signs Measurements
Including systolic and diastolic blood pressure and heart rate
Measured: Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 4hrs, 12hrs, 24hrs, Follow-up (7 to 14 days after last dose)
Adverse Events
Measured: From administration of first dose until follow-up (7 to 14 days after last dose)
Clinical Laboratory Tests
Including clinical chemistry, haematology and urinalysis tests
Measured: Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 24hrs, Follow-up (7 to 14 days after last dose)
12-lead ECG measurements
Measured: Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 4hrs, 12hrs, 24hrs, Follow-up (7 to 14 days after last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2012 (estimated)
- Study start29 Mar 2012
- Primary completion22 Jun 2012
- Study completion22 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01571999
- Sponsor's protocol ID
- 114636
- Status last verified
- Jul 2017
- First submitted
- 3 Apr 2012
- Last updated
- 25 Jul 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
Mehta R, Hardes K, Brealey N, Tombs L, Preece A, Kelleher D. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study. Int J Chron Obstruct Pulmon Dis. 2014 Dec 18;10:15-23. doi: 10.2147/COPD.S68094. eCollection 2015.
PubMed 25565796
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-blind, Non-randomized Pharmacokinetic and Safety Study of Single Dose of GSK573719 and GSK573719 + GW642444 Combination in Healthy Subjects and in Subjects With Severe Renal Impairment
- ClinicalTrials.gov ID
- NCT01571999
- Acronym / sponsor ID
- 114636
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- pharmacokinetics, GW642444, GSK573719, vilanterol, renal impairment, safety, COPD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2012 (actual)
- Primary completion
- 22 Jun 2012 (actual)
- Study completion
- 22 Jun 2012 (actual)
- First posted
- 5 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety and pharmacokinetics of inhaled GSK573719 and GSK573719/vilanterol combination in healthy subjects and in subjects with severe renal impairment. The results of the study will provide guidance on the use of this product in subjects with severe renal impairment.
Detailed description
GSK573719 monotherapy and GSK573719/vilanterol combination are currently under development for the treatment of COPD. This study will assess the pharmacokinetics and safety of inhaled GSK573719 and GSK573719/vilanterol (VI) in healthy subjects and in subjects with severe renal impairment. Nine subjects with severe renal impairment (as defined by a Clcr<30mL/min) will be recruited along with healthy control subjects (as defined by a Clcr>80mL/min matched to the severe renal impairment subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years)). The results from this study will provide guidance on the use of GSK573719 and GSK573719/VI in severe renally impaired patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Severe renally impaired subjects | Experimental | Drug: Inhaled GSK573719, Drug: Inhaled GSK573719/vilanterolApproximately 9 subjects will complete each treatment arm |
| Matched healthy volunteers | Experimental | Drug: Inhaled GSK573719, Drug: Inhaled GSK573719/vilanterolMatched to the severe renal impairment subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years). Approximately 9 subjects will complete each treatment arm |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or, child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol for an appropriate period of time prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until follow-up.
- Body weight greater than or equal to 45 kg and body mass index (BMI) within the range 18 - 33 kg/m2 (inclusive)
- Single QTcF less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.
Key exclusion criteria (31 listed)
- Suffered a lower respiratory tract infection in the 4 weeks before the screening visit
- A supine mean heart rate outside the range 40-90 beats per minute (BPM) at screening
- A positive pre-study drug/alcohol screen
- A positive test for HIV antibody
- Current or chronic history of liver disease, including documented cirrhosis or a history consistent with a diagnosis of cirrhosis, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled GSK573719All subjects will receive a single dose of GSK573719 (125mcg) in treatment period 1 | Drug | Matched healthy volunteers, Severe renally impaired subjects |
| Inhaled GSK573719/vilanterolAll subjects will receive a single dose of GSK573719 (125mcg)/vilanterol (25mcg) in treatment period 2 | Drug | Matched healthy volunteers, Severe renally impaired subjects |
Primary outcome
GSK573719 and vilanterol plasma pharmacokinetic parameters
Time frame: Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 2hrs, 4hrs, 8hrs, 12hrs, 16hrs, 24hrs
Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2
5 secondary outcomes
GSK573719 urine pharmacokinetic parameters
Time frame: Treatment Period 1 and 2: 0-4hrs, 4-8hrs, 8-12hrs, 12-24hrs
Vital Signs Measurements
Time frame: Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 4hrs, 12hrs, 24hrs, Follow-up (7 to 14 days after last dose)
Adverse Events
Time frame: From administration of first dose until follow-up (7 to 14 days after last dose)
Clinical Laboratory Tests
Time frame: Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 24hrs, Follow-up (7 to 14 days after last dose)
12-lead ECG measurements
Time frame: Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 4hrs, 12hrs, 24hrs, Follow-up (7 to 14 days after last dose)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2017.
- Derived from this study: PubMed 25565796Mehta R, Hardes K, Brealey N, Tombs L, Preece A, Kelleher D. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study. Int J Chron Obstruct Pulmon Dis. 2014 Dec 18;10:15-23. doi: 10.2147/COPD.S68094. eCollection 2015.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 114636 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Inhaled GSK573719 and Inhaled GSK573719/vilanterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 2 sites in 2 countries.
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 13 inclusion and 31 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 25 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Czechia, Hungary. 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?
GSK573719 and vilanterol plasma pharmacokinetic parameters (time frame: Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 2hrs, 4hrs, 8hrs, 12hrs, 16hrs, 24hrs). 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 NCT01571999, 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 25 Jul 2017.