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Pulmonary Disease, Chronic ObstructivePhase 1NCT01266980

A Study to Assess the Effects of Repeat Doses of Fluticasone Furoate and GW642444M Combination in Healthy Subjects and in Subjects With Severe Impairment.

A Phase 1 study testing Inhaled FF/ GW642444M (200/25mcg) in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Czechia.

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

This study will assess the saftey of giving fluticasone furoate 200mcg/GW642444M 25mcg once daily for 7 days to patients with severe renal imparement. The results of this study will aid in deciding whether a FF/GW642444M doseadjustment is justified in subjects with severe renal impairment and in estimating any such… 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 FF/ GW642444M (200/25mcg)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteCzechia
Study dates
18 Nov 2010to 22 Mar 2011
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

  • A subject will be eligible for inclusion in this study only if all of the following criteria apply:
  • 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 [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) (healthy subjects only) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
  • Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until completion of the follow-up visit.
  • BMI within the range 19.0 - 33.0 kg/m^2 (inclusive).
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  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Single QTcF < 450 msec; or QTcF < 480 msec in subjects with Bundle Branch Block.
  • Able to satisfactorily use the dry powder inhaler.
  • Healthy Subjects:
  • 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 being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcome.
  • AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Creatinine clearance > 80mL/min calculated by the Cockcroft-Gault equation using serum creatinine.
  • Renally Impaired Subjects:
  • AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Creatinine clearance < 30mL/min calculated by the Cockcroft-Gault equation using serum creatinine.
  • Subjects with renal insufficiency must have stable renal function defined as ≤ 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 (historic data is permitted for the first measurement).

Who cannot join

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • Suffered a lower respiratory tract infection in the 4 weeks before the screening visit.
  • Taken oral corticosteroids less than 8 weeks before the screening visit.
  • Taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
  • Any subject with either documented cirrhosis or a history consistent with a diagnosis of cirrhosis.
  • A positive pre-study drug/alcohol screen.
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  • 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.
  • 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.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Subjects with smoking history of >10 cigarettes per day or regular use of tobacco- or nicotine-containing products, within 6 months prior to screening.
  • History of severe milk protein allergy.
  • Any adverse reaction including immediate or delayed hypersensitivity to any beta2- agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the Novel DPI (i.e., lactose or magnesium stearate). History of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • 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:
  • If, in the opinion of the examining physician, an unstable cardiovascular, renal, hepatic, pulmonary, endocrine, metabolic, neurological, haematological or gastrointestinal 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.
  • Subjects with any predisposing condition that might interfere with the absorption, distribution, metabolism or excretion of drugs or any previous gastrointestinal (GI) surgery (except appendectomy or cholecystectomy more than three months prior to the study) or condition (including pancreatitis or acute cholecystitis) 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 >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
  • Hemoglobin or hematocrit below the reference range at screening.
  • 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 inhibitor) 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.
  • 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 (see Section 9 for the list of permitted concurrent medications). 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

1 site in 1 country.

Czechia1 site

  • GSK Investigational Site

    Prague, 170 00

Other trials in Czechia

About this study

Official title: An Open-label, Non-randomized Pharmacokinetic and Safety Study of Repeat Doses of Fluticasone Furoate and GW642444M Combination in Healthy Subjects and in Subjects With Severe Renal Impairment.

This study will assess the saftey of giving fluticasone furoate 200mcg/GW642444M 25mcg once daily for 7 days to patients with severe renal imparement. The results of this study will aid in deciding whether a FF/GW642444M doseadjustment is justified in subjects with severe renal impairment and in estimating any such adjustments.

Read the detailed description

This is an open-label, non-randomized study which will assess the pharmacokinetics and safety following 7 days once daily dose of inhaled FF/ GW642444M (200/25mcg) in subjects with 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 subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years)). All subjects will receive fluticasone furoate 200mcg/GW642444M 25mcg once daily for 7 days. The results of this study will aid in deciding whether a FF/GW642444M dose adjustment is justified in subjects with severe renal impairment and in estimating any such adjustments.

Being tested
Inhaled FF/ GW642444M (200/25mcg)
Keywords
cortisol, renal impairment, serum potassium, pharmacokinetics, Fluticasone furoate, heart rate
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 FF/ GW642444M (200/25mcg)Drug

    All subjects will be assigned to take FF/ GW642444M (200/25mcg) combination once daily for 7 days.

Study groups in NCT01266980
Study groupRoleWhat they receive
Severe Renal ImparementExperimentalNine subjects with severe renal impairment (as defined by a Clcr<30mL/min) will be recruited for this study. they will receive FF/ GW642444M (200/25mcg) once daily for 7 days.
Receives: Drug: Inhaled FF/ GW642444M (200/25mcg)
Matched healthy volunteersExperimentalFor each of the 9 renally impaired subjects a healthy control subject (as defined by a Clcr>80mL/min matched to the severe subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years)) will be recuited. They will receive FF/ GW642444M (200/25mcg) once daily for 7 days.
Receives: Drug: Inhaled FF/ GW642444M (200/25mcg)

What is being measured

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

  1. Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC (0-8),Cmax, tmax,) on Day 1 and 7 and AUC(0-24) and t½ on Day 7.

    Measured: 1 Month

Secondary outcomes (4)

  1. Serum cortisol weighted mean over 24 hours on Days -1 and 7

    Measured: 1 Month

  2. Maximum heart rate over time period 0-4 hours on Day 7.

    Measured: 1 Month

  3. Minimum serum potassium values over time period 0-4 hours on Day 7.

    Measured: 1 Month

  4. General safety and tolerability endpoints: adverse events, blood pressure, heart rate, 12-lead ECG, clinical laboratory safety tests.

    Measured: 1 Month

Timeline

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

  1. First posted24 Dec 2010 (estimated)
  2. Study start18 Nov 2010
  3. Primary completion22 Mar 2011
  4. Study completion22 Mar 2011

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
Basic science
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01266980
Sponsor's protocol ID
113970
Status last verified
Aug 2017
First submitted
23 Dec 2010
Last updated
3 Aug 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

  • Allen A, Davis A, Hardes K, Tombs L, Kempsford R. Influence of renal and hepatic impairment on the pharmacokinetic and pharmacodynamic properties and tolerability of fluticasone furoate and vilanterol in combination. Clin Ther. 2012 Dec;34(12):2316-32. doi: 10.1016/j.clinthera.2012.11.001. Epub 2012 Nov 30.

    PubMed 23200625

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Inhaled FF/ GW642444M (200/25mcg) in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Czechia.

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 17 inclusion and 38 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 3 Aug 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 Czechia. 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?

Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC (0-8),Cmax, tmax,) on Day 1 and 7 and AUC(0-24) and t½ on Day 7. (time frame: 1 Month). 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 NCT01266980, 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 3 Aug 2017; AzTrials last refreshed its copy on 6 Nov 2026.

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