Pulmonary Disease, Chronic ObstructivePhase 1NCT01577680
A Study to Assess the Effects of GSK573719/VI Combination and GSK573719 Monotherapy in Subjects With Moderate Hepatic Impairment and Matched Healthy Volunteers
A Phase 1 study testing Inhaled GSK573719/vilanterol and Inhaled GSK573719 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 GSK573719 and GSK573719/vilanterol combination in healthy subjects and subjects with moderate hepatic impairment. The results of this study will provide guidance on the use of the product in patients with hepatic 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/vilanterol and Inhaled GSK573719
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 5 Mar 2012to 29 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 Child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol
- Body weight of greater than or equal to 45 kg and body mass index 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.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Healthy Subjects
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- ALT, alkaline phosphatase and bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN)
- Healthy as determined by a responsible and experienced physician Hepatically Impaired Subjects
- Moderately hepatically impaired - subjects must have a known medical history of liver disease with or without a known history of alcohol abuse, and a Child-Pugh score of 7-9 points
- Subjects with no significant abnormality, apart from impaired hepatic function and related symptoms, or clinical examination.
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.
- 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).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
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- 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.
- 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
- 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.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- 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.
- The subject is unable to use the novel dry powder inhaler correctly 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 condition 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.
- 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 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
- Hepatically impaired subjects:
- If in the opinion of the examining physician, an unstable cardiovascular, renal, pulmonary, endocrine, metabolic, neurological, haematological or gastrointestinal condition is present or any other significant 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.
- Severe ascities (Child-Pugh ascites score of 3) upon clinical exam, including physical exam and abdominal ultrasound at screening. Subjects identified to have moderate ascities by ultrasound examination may be included at the discretion of the Investigator with prior agreement from the sponsor.
- History of oesophageal bleeding within the last 6 months before dosing.
- Significant hepatic encephalopathy, degree of CNS impairment or other signs of hepatic function deterioration which the investigator considers sufficiently serious to interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
- Patients at risk of requiring a transfusion during the study period, or has haemoglobin less than 9 g/dL
- Evidence of current significant infection
- Subjects who develop symptoms such as infections or haemorrhage between screening and dosing must not be included in the study
- Fluctuating or rapidly deteriorating hepatic function
- Subjects with significant renal insufficiency as defined by estimated creatinine clearance of less than 50 ml/min, using the Cockcroft and Gault equation
- Subjects with a diagnosis of primary biliary disease such as cholestasis or sclerosing cholangitis
- 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. ketoconazole) must not be included in this study
- Subjects who, within the past six months, have had a history of significant drug abuse or alcohol abuse.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: An Open-label, Non-randomized, Pharmacokinetic and Safety Study of Single Dose GSK573719 + GW643444 (VI) Combination and Repeat Doses of GSK573719 in Healthy Subjects and in Subjects With Moderate Hepatic Impairment
This study will assess the safety and pharmacokinetics of GSK573719 and GSK573719/vilanterol combination in healthy subjects and subjects with moderate hepatic impairment. The results of this study will provide guidance on the use of the product in patients with hepatic impairment.
Read the detailed description
GSK573719 is being developed as a monotherapy and in combination with vilanterol for the treatment of Chronic Obstructive Pulmonary Disease (COPD). This study will assess the pharmacokinetics and safety of inhaled GSK573719/ vilanterol (VI) and GSK573719 in healthy subjects and in subjects with moderate hepatic impairment. Nine subjects with moderate hepatic impairment will be recruited, together with nine matched healthy volunteers.
There is a possibility that when used by patients with impaired hepatic function the pharmacokinetics of inhaled GSK573719 or GSK572719/VI may be altered. The results of this study will therefore provide guidance on the use of GSK573719 and GSK573719/VI in moderate hepatically impaired patients.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Inhaled GSK573719/vilanterol, Inhaled GSK573719
- Keywords
- healthy subjects, pharmacokinetics, vilanterol, tolerability, safety, hepatic impairment, GW642444, GSK573719
- 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.
Inhaled GSK573719/vilanterolDrug
All subjects will receive a single dose of GSK573719/VI (125mcg/25mcg) in Treatment Period 1
Inhaled GSK573719Drug
All subjects will receive GSK573719 (125mcg) once daily for seven days in Treatment Period 2
| Study group | Role | What they receive |
|---|---|---|
| Moderate Hepatic Impairment | Experimental | Approximately 9 subjects will complete each of these treatment arms Receives: Drug: Inhaled GSK573719/vilanterol; Drug: Inhaled GSK573719 |
| Matched Healthy Volunteers | Experimental | Matched to the moderate hepatic impairment subjects based on gender, ethnicity, body mass index (+/-15%) and age (+/-5 years) Approximately 9 subjects will complete each of these treatment arms Receives: Drug: Inhaled GSK573719/vilanterol; Drug: Inhaled GSK573719 |
What is being measured
The primary outcome is the main question the study is designed to answer.
GSK573719 and vilanterol pharmacokinetics
Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2 (following single dose administration)
Measured: Treatment Period 1: Pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 16 hrs, 24 hrs
GSK573719 pharmacokinetics
Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2 (following single and repeat dose administration)
Measured: Treatment Period 2 (Day 1 and 7): Pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 2hrs, 4 hrs, 8 hrs, 12hrs, 16 hrs, 24 hrs (and 36 hrs on Day 7 only)
Secondary outcomes (6)
Urine pharmacokinetics for GSK573719 (Treatment Period 1)
Including amount excreted in urine in 24 hrs (following single dose administration)
Measured: 0-4hrs, 4-8hrs, 8-12hrs and 12-24hrs
Urine pharmacokinetics for GSK573719 (Treatment Period 2)
Including amount excreted in urine in 24 hrs (following single and repeat dose administration)
Measured: Days 1 and 7: 0-4hrs, 4-8hrs, 8-12hrs, 12-24hrs (and 24-36hrs on Day 7 only)
Measurement of vital signs
Including systolic and diastolic blood pressure and heart rate
Measured: Screening (up to 21 days before dosing), Treatment Period 1 and Treatment Period 2 (Day 1 and 7): pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 4 hrs, 12 hrs, 24 hrs, Follow-up (7 to 14 days after last dose)
Adverse Events
Measured: Adverse events will be recorded from the start of dosing to follow-up (7 to 14 days after last dose), an average expected duration of 4 weeks
Clinical Laboratory Safety Tests
Including haematology, clinical chemistry and urinalysis tests
Measured: Screening (up to 21 days before dosing), Treatment Period 1: pre-dose, 24 hrs, Treatment Period 2 (Day 1 and 7): pre-dose, 24 hrs, Day 4 hepatic subjects only, 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 Treatment Period 2 (Day 1 and 7): pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 4hrs, 12hrs, 24hrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2012 (estimated)
- Study start5 Mar 2012
- Primary completion29 Jun 2012
- Study completion29 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- None (open label)
- Enrolment
- 18 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
- NCT01577680
- Sponsor's protocol ID
- 114637
- Status last verified
- Jul 2017
- First submitted
- 29 Mar 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.
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
- An Open-label, Non-randomized, Pharmacokinetic and Safety Study of Single Dose GSK573719 + GW643444 (VI) Combination and Repeat Doses of GSK573719 in Healthy Subjects and in Subjects With Moderate Hepatic Impairment
- ClinicalTrials.gov ID
- NCT01577680
- Acronym / sponsor ID
- 114637
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- healthy subjects, pharmacokinetics, vilanterol, tolerability, safety, hepatic impairment, GW642444, GSK573719
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 5 Mar 2012 (actual)
- Primary completion
- 29 Jun 2012 (actual)
- Study completion
- 29 Jun 2012 (actual)
- First posted
- 16 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 GSK573719 and GSK573719/vilanterol combination in healthy subjects and subjects with moderate hepatic impairment. The results of this study will provide guidance on the use of the product in patients with hepatic impairment.
Detailed description
GSK573719 is being developed as a monotherapy and in combination with vilanterol for the treatment of Chronic Obstructive Pulmonary Disease (COPD). This study will assess the pharmacokinetics and safety of inhaled GSK573719/ vilanterol (VI) and GSK573719 in healthy subjects and in subjects with moderate hepatic impairment. Nine subjects with moderate hepatic impairment will be recruited, together with nine matched healthy volunteers.
There is a possibility that when used by patients with impaired hepatic function the pharmacokinetics of inhaled GSK573719 or GSK572719/VI may be altered. The results of this study will therefore provide guidance on the use of GSK573719 and GSK573719/VI in moderate hepatically impaired patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Moderate Hepatic Impairment | Experimental | Drug: Inhaled GSK573719/vilanterol, Drug: Inhaled GSK573719Approximately 9 subjects will complete each of these treatment arms |
| Matched Healthy Volunteers | Experimental | Drug: Inhaled GSK573719/vilanterol, Drug: Inhaled GSK573719Matched to the moderate hepatic impairment subjects based on gender, ethnicity, body mass index (+/-15%) and age (+/-5 years) Approximately 9 subjects will complete each of these treatment arms |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 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 Child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol
- Body weight of greater than or equal to 45 kg and body mass index 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 (33 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.
- 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).
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 GSK573719/vilanterolAll subjects will receive a single dose of GSK573719/VI (125mcg/25mcg) in Treatment Period 1 | Drug | Matched Healthy Volunteers, Moderate Hepatic Impairment |
| Inhaled GSK573719All subjects will receive GSK573719 (125mcg) once daily for seven days in Treatment Period 2 | Drug | Matched Healthy Volunteers, Moderate Hepatic Impairment |
Primary outcome
GSK573719 and vilanterol pharmacokinetics
Time frame: Treatment Period 1: Pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 16 hrs, 24 hrs
Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2 (following single dose administration)
GSK573719 pharmacokinetics
Time frame: Treatment Period 2 (Day 1 and 7): Pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 2hrs, 4 hrs, 8 hrs, 12hrs, 16 hrs, 24 hrs (and 36 hrs on Day 7 only)
Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2 (following single and repeat dose administration)
6 secondary outcomes
Urine pharmacokinetics for GSK573719 (Treatment Period 1)
Time frame: 0-4hrs, 4-8hrs, 8-12hrs and 12-24hrs
Urine pharmacokinetics for GSK573719 (Treatment Period 2)
Time frame: Days 1 and 7: 0-4hrs, 4-8hrs, 8-12hrs, 12-24hrs (and 24-36hrs on Day 7 only)
Measurement of vital signs
Time frame: Screening (up to 21 days before dosing), Treatment Period 1 and Treatment Period 2 (Day 1 and 7): pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 4 hrs, 12 hrs, 24 hrs, Follow-up (7 to 14 days after last dose)
Adverse Events
Time frame: Adverse events will be recorded from the start of dosing to follow-up (7 to 14 days after last dose), an average expected duration of 4 weeks
Clinical Laboratory Safety Tests
Time frame: Screening (up to 21 days before dosing), Treatment Period 1: pre-dose, 24 hrs, Treatment Period 2 (Day 1 and 7): pre-dose, 24 hrs, Day 4 hepatic subjects only, 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 Treatment Period 2 (Day 1 and 7): pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 4hrs, 12hrs, 24hrs
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.
- 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 114637 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/vilanterol and Inhaled GSK573719 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 10 inclusion and 33 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 Hungary, Slovakia. 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 pharmacokinetics (time frame: Treatment Period 1: Pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 16 hrs, 24 hrs). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.