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AsthmaPhase 1NCT01725685

To Investigate the Pharmacokinetics and Safety of Fluticasone Furoate (FF)/ Umeclidinium (UMEC) Combination Compared With FF and UMEC Monotherapies in Adult Healthy Volunteers Using a Dry Powder Inhaler (DPI)

A Phase 1 study testing FF 400 mcg, UMEC 500 mcg and FF/UMEC 400/500 mcg in people with Asthma, run by GlaxoSmithKline at 1 site in United States.

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 will be a randomized, double-blind, single-dose, three-period balanced crossover study in adult healthy subjects. Each of the 18 subjects will be randomized to receive a treatment sequence consisting of each of the three treatments (FF 400 microgram (mcg), UMEC 500 mcg and FF 400 mcg/UMEC 500 mcg), in three… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Asthma
What is being tested?
FF 400 mcg, UMEC 500 mcg and FF/UMEC 400/500 mcg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
8 Nov 2012to 2 Jan 2013
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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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 GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of: Child-bearing potential and is abstinent or agrees to use the contraception methods listed in Protocol 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 the follow up visit (i.e. until after the follow up visit is complete; 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 million international units (MlU)/milliliter (ml) and estradiol <40 picograms (pg)/ml (<147 pmol/L) is confirmatory] Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use the contraception methods listed in Protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks should 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.
  • Women who are confirmed postmenopausal or permanently sterilized (e.g. tubal occlusion, tubal ligation, hysterectomy, bilateral salpingectomy).
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit.
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  • Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Average QT duration corrected for heart rate by Fridericia's formula (QTcF) < 450 miliseconds (msec).
  • Body mass index (BMI) within the range 19 to 33 kilogram (kg)/meter square (m2) (inclusive).
  • Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of ≤10 pack years.[number of pack years = (number of cigarettes per day /20) x number of years smoked]

Who cannot join

  • 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.
  • A positive pre-study drug/alcohol screen.
  • A positive test for human Immunodeficiency virus (HIV) antibody.
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mililitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
  • 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.
  • 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.
  • 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.
  • 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.
  • History of respiratory disease (i.e. history of asthmatic symptoms) in the last 10 years.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  • Known or suspected sensitivity to the constituents of the DPI or a history of severe milk protein allergy.
  • A supine mean heart rate outside the range 40 to 90 beats per minute (bpm) at screening.
  • Diseases preventing use of anticholinergics: Diagnosis of narrow-angle glaucoma, or bladder neck obstruction that in the opinion of the study investigator or GSK medical monitor would pose a safety risk with use of an inhaled anticholinergic.
  • Other concurrent diseases/abnormalities: A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation if the condition/disease exacerbated during the study. The investigator is encouraged to contact the study medical monitor if further clarification is required.
  • Affiliation with the investigators site

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Baltimore, Maryland, 21225

Other trials in United States

About this study

Official title: A Randomized, Double Blind, Single-dose, Three-period, Crossover Study to Investigate Pharmacokinetic, Safety and Tolerability of Fluticasone Furoate With Umeclidinium When Administered in Combination and as Monotherapies in Adult Healthy Volunteer Subjects

This will be a randomized, double-blind, single-dose, three-period balanced crossover study in adult healthy subjects. Each of the 18 subjects will be randomized to receive a treatment sequence consisting of each of the three treatments (FF 400 microgram (mcg), UMEC 500 mcg and FF 400 mcg/UMEC 500 mcg), in three consecutive periods, with a wash-out period of 7 to 10 days between the periods.

The study will include a Screening period (28 days prior to first dose), Treatment period (3 single dose periods separated by two 7 to 10 days washout periods) and Follow-up period (7 to 14 days post last dose).

The pharmacokinetic (PK) and safety assessments will be performed during the study at fixed timepoints.

Conditions
Asthma
Being tested
FF 400 mcg, UMEC 500 mcg, FF/UMEC 400/500 mcg
Keywords
healthy volunteers, Umeclidinium, tolerability, Safety, Fluticasone Furoate, Pharmacokinetics
Medical subject headings
Asthma

What participants receive

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

  • FF 400 mcgDrug

    FF will be available as 100 mcg strength administered as 4 inhalations from a DPI

  • UMEC 500 mcgDrug

    UMEC will be available as 125 mcg strength administered as 4 inhalations from a DPI

  • FF/UMEC 400/500 mcgDrug

    FF/UMEC will be available as 100/125 mcg strength administered as 4 inhalations from a DPI

Study groups in NCT01725685
Study groupRoleWhat they receive
Treatment A - FF 400 microgram (mcg)ExperimentalSubjects will be randomized to single dose of FF 400 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.
Receives: Drug: FF 400 mcg
Treatment B - UMEC 500 mcgExperimentalSubjects will be randomized to single dose of UMEC 125 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.
Receives: Drug: UMEC 500 mcg
Treatment C - FF/UMEC 400/500 mcgExperimentalSubjects will be randomized to single dose of FF/UMEC 100/125 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.
Receives: Drug: FF/UMEC 400/500 mcg

What is being measured

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

  1. Maximum observed plasma concentration (Cmax) in plasma for FF and UMEC

    The PK parameter Cmax will be calculated for FF/UMEC in combination and as monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 minutes [mins], 15 mins, 30 mins, 45 mins, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  2. Area under the concentration-time curve (AUC(0-t)), where t is time of last measurable concentration in plasma for FF and UMEC

    The PK parameter AUC(0-t) will be calculated for will be calculated for FF/UMEC in combination and as monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  3. Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-inf)] in plasma for FF and UMEC, if data permits

    The PK parameter AUC(0-inf) will be calculated for will be calculated for FF/UMEC in combination and as monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  4. Time of maximum observed concentration (tmax) in plasma for FF and UMEC

    The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  5. Time of last measurable concentration (tlast) in plasma for FF and UMEC

    The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  6. Plasma elimination half life (t½) in plasma for FF and UMEC, if data permits

    The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  7. Elimination rate constant (Lambda z) in plasma for FF and UMEC, if data permits

    The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  8. Apparent clearance (CL/F) in plasma for FF and UMEC, if data permits

    The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  9. Apparent volume of distribution (V/F) in plasma for FF and UMEC, if data permits

    The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

  10. Cumulative amount excreted drug in urine (Ae) for UMEC

    The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2(0-24 h)

  11. Percent of dose excreted (% Fe) in urine for UMEC

    The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2 (0-24 h)

  12. Urine half life (urine t½) for UMEC, if data permits

    The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2 (0-24 h)

  13. Renal clearance (CLr) in urine for UMEC, if data permits

    The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 6-8 h, 8-12 h, 12-16 h) and Day 2(16-24 h)

  14. Area under the concentration-time curve from time zero (pre-dose) to the time at which AUC is calculable for all subjects (AUC(0-t')), where t' is the time at which AUC is calculable for all the subjects

    The PK parameter AUC(0-t') will be calculated for will be calculated for FF/UMEC in combination and as monotherapies

    Measured: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)

Secondary outcomes (5)

  1. Clinical Safety data assessed as number of adverse events (AE) in each treatment group

    Safety and tolerability will be assessed by recording of AEs for subjects receiving FF/UMEC in combination compared with FF and UMEC monotherapies.

    Measured: Period 1 Day 1 dose to Follow up visit

  2. Clinical laboratory measurements for each treatment group

    Safety and tolerability will be assessed by measuring the clinical laboratory parameters which include hematology, clinical chemistry, routine urinalysis and additional parameters.

    Measured: Period 1, 2 and 3: Baseline (Day -1) and Day 2

  3. Systolic and diastolic blood pressure for each treatment group

    Safety and tolerability will be assessed by measuring vital signs which include systolic and diastolic blood pressure.

    Measured: Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit

  4. Heart rate for each treatment group

    Safety and tolerability will be assessed by measuring vital signs which include heart rate.

    Measured: Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit

  5. 12-lead electrocardiogram (ECG) for each treatment group

    Safety and tolerability will be assessed by measuring ECG using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals.

    Measured: Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit

Timeline

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

  1. First posted14 Nov 2012 (estimated)
  2. Study start8 Nov 2012
  3. Primary completion2 Jan 2013
  4. Study completion2 Jan 2013

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
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01725685
Sponsor's protocol ID
116524
Status last verified
Jun 2017
First submitted
1 Nov 2012
Last updated
9 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

  • Yang S, Lee L, Mallett S, Ayer J, Wolstenholme A, Pascoe S. A randomized, crossover study to investigate the pharmacokinetics and safety of inhaled fluticasone furoate and umeclidinium, administered separately and in combination via dry powder inhaler in healthy adult volunteers. Adv Ther. 2015 Feb;32(2):157-71. doi: 10.1007/s12325-015-0184-6. Epub 2015 Feb 21.

    PubMed 25700806

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FF 400 mcg, UMEC 500 mcg and FF/UMEC 400/500 mcg in people with Asthma, run by GlaxoSmithKline at 1 site in United States.

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 23 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 9 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 United States. 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?

Maximum observed plasma concentration (Cmax) in plasma for FF and UMEC (time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 minutes [mins], 15 mins, 30 mins, 45 mins, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)). The study lists 14 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 NCT01725685, 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 9 Jun 2017.

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