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Pulmonary Disease, Chronic ObstructivePhase 1NCT02837380

A Phase I Pharmacokinetic Study of Fluticasone Furoate /Umeclidinium Bromide/Vilanterol (100/62.5/25 Microgram [mcg]) After Single and Repeat Dose Administration From a Dry Powder Inhaler in Healthy Chinese Subjects

A Phase 1 study testing FF and VI/UMEC in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in China.

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 is an open-label study to evaluate the PK of FF/UMEC/VI in dose combinations of 100/62.5/25 mcg after single and repeat dose administration from a DPI in healthy Chinese subjects. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
FF and VI/UMEC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteChina
Study dates
Sep 2016to Nov 2016
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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • No significant abnormality on 12-lead ECG at screening, including the following specific requirements: Ventricular rate inside the range 40-90 beats (inclusive) per minute (bpm) at screening, PR interval <=210milliseconds (msec), No pathological Q waves, QRS interval >=60 msec and <=120 msec, the waveforms must enable the QT interval to be clearly defined and the corrected QT interval by Fridericia's method (QTcF) must be <450msec (machine or manual reading) based on a single ECG value, or an average from three ECGs obtained over a brief recording period.
  • Forced Expiratory Volume in 1 second (FEV1) >=80% predicted and a FEV1/Forced Vital Capacity (FVC) ratio >=0.7
  • AST, ALT, ALP and bilirubin <=1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Male/females aged between 18 and 45 years of age (inclusive), at the time of signing the informed consent. Male and female is 1:1.
  • Body weight >=50 Kilogram (Kg) and Body Mass Index (BMI) within the range 19-24 Kg per square meter (m^2) (inclusive).
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and lung function testing. 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 considers the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures and outcome.
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  • Subjects who are current non-smokers and have not used any tobacco products in the 6 month period preceding screening and have a pack history of <=10 pack years.
  • [Number of pack years = (number of cigarettes per day /20) x number of years smoked]
  • Capable of giving written informed consent.
  • A female subject is eligible to participate if: she is of child-bearing potential and is abstinent or agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the chance of pregnancy at that point or She must agree to use contraception until the follow-up visit (i.e. until follow-up visit is complete) or she is on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods 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 2-4 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 or she is confirmed postmenopausal or permanently sterilised (example [e.g.] tubal occlusion, tubal ligation, hysterectomy, bilateral salpingectomy).

Who cannot join

  • Lactating or pregnant females as determined by positive serum or urine human chorionic gonadotropin (HCG) test at screening or prior to dosing.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities or a history of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a 285 milliliter (mL) glass of full strength beer or 425 mL schooner of low strength beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine
  • History of chronic respiratory problems (i.e. history of asthmatic symptoms) in the last 10 years or suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
  • A positive pre-study Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody result within 3 months of screening or a positive test for Human Immunodeficiency Virus (HIV) antibody or Syphilis antibody.
  • 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 the medication will not interfere with the study procedures or compromise subject safety.
  • A positive pre-study drug/alcohol screen or on admission to the Unit.
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  • 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) or has had exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unwillingness or inability to follow the study procedures outlined in the protocol.
  • The subject is unable to refrain from the consumption of red wine, seville oranges, grapefruit or grapefruit juice and pummelos, exotic citrus fruits, grapefruit hybrids or any fruit juices containing these fruits from 7 days prior to the first dose of study medication and for the duration of the study.
  • Mentally or legally incapacitated.
  • History of allergy or hypersensitivity to heparin, or any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta-2 agonist, lactose/milk protein or magnesium stearate or a history of drug allergy or other allergy that, in the opinion of the investigator, contraindicates their participation.
  • A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities. A chest X-ray must be taken before Day1, in any day between screening and Day -1(inclusive) if a chest X-ray or CT scan is not available within 6 months prior to screening day.

Trial locations and contacts

1 site in 1 country.

China1 site
  • GSK Investigational Site

    Shanghai, 200030

Other trials in China

About this study

Official title: An Open Label Study to Evaluate the Pharmacokinetics of Fluticasone Furoate /Umeclidinium Bromide/Vilanterol (100/62.5/25 mcg) After Single and Repeat Dose Administration From a Dry Powder Inhaler in Healthy Chinese Subjects

This is an open-label study to evaluate the PK of FF/UMEC/VI in dose combinations of 100/62.5/25 mcg after single and repeat dose administration from a DPI in healthy Chinese subjects. This study will evaluate the systemic pharmacokinetics (PK), of FF/UMEC/VI in Chinese healthy population when administered using dry powder inhaler (DPI)as a blended combination of UMEC/VI in one strip and FF in the second strip in dose combinations of 100/62.5/25 mcg. The triple, fixed dose combination product Fluticasone furoate(FF)/ Vilanterol (VI) /Umeclidinium bromide (UMEC) with new configuration enables the delivery of inhaled long-acting muscarinic antagonist (LAMA), Long-acting beta2 agonist (LABA) and inhaled corticosteroid (ICS) from a single device. Approximately 16 subjects will be enrolled in the study. After taking into account the allowable time windows for screening, treatment and follow-up, a subject will be in the study for a maximum duration of 6-7 weeks.

Being tested
FF, VI/UMEC
Keywords
Long-acting muscarinic antagonist, Long-acting beta2 agonist, Dry powder inhaler, Inhaled corticosteroid
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.

  • FFDrug

    FF is a dry white powder blended with lactose. It is the first strip of DPI. Per blister contains 100 mcg of dose

  • VI/UMECDrug

    VI and UMEC bromide combination is a dry white powder blended with lactose and magnesium stearate. It is the second strip of DPI. Per blister contains 25 mcg/62.5 mcg of VI/UMEC dose

Study groups in NCT02837380
Study groupRoleWhat they receive
FF/UMEC/VIExperimentalSubjects will receive single combination dose of FF/UMEC/VI 100/62.5/25 mcg via a DPI in the morning for 7 days.
Receives: Drug: FF; Drug: VI/UMEC

What is being measured

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

  1. Maximum observed concentration (Cmax) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 minutes (min), 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  2. Time of occurrence of Cmax (tmax) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  3. Area under the concentration time curve (AUC) between zero and the time to the last measurable concentration (AUC (0-t)) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  4. AUC from time zero (pre-dose) to the time of last common measurable time-point within subject /treatment/study (AUC (0-t')) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  5. Elimination rate constant (kel) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  6. Terminal half-life (t1/2) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  7. AUC between zero and the infinity (AUC (0-inf)) of FF, UMEC and VI after single inhaled dose on Day1

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1

  8. tmax after repeat inhaled dose of FF, UMEC and VI on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  9. AUC (0-t) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  10. AUC (0-t') of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  11. Maximum concentration observed at steady state (Css_max) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  12. Minimum concentration observed at steady state (Css_min) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  13. Average steady state concentration (Css_av) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  14. AUC at steady state (AUCss) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  15. Observed accumulation ratio (Ro) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  16. Maximum observed concentration ratio (RCmax) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

  17. Degree of fluctuation (DF) of FF, UMEC and VI after repeat inhaled dose on Day 7

    Measured: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7

Secondary outcomes (7)
  1. Number of subjects with any Adverse Events (AEs) and any serious adverse events (SAEs)

    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement and associated with liver injury and impaired liver function will be categorized as SAE.

    Measured: Up to Day 17

  2. Pulse rate as a measure of safety

    Pulse rate will be taken in sitting position having rested in this position for at least 5 minutes

    Measured: Up to Day 17

  3. Systolic and diastolic blood pressure as a measure of safety

    Systolic and diastolic blood pressure will be taken in sitting position having rested in this position for at least 5 minutes

    Measured: Up to Day 17

  4. Electrocardiogram (ECG) as a measure of safety

    12-Lead ECG will be taken in a supine position, having rested in this position for at least 5 minutes.

    Measured: Up to Day 17

  5. Number of subjects with abnormal hematology values

    Hematological parameters includes: platelet count, red blood cell (RBC) count, absolute white blood cell (WBC) count, hemoglobin, hematocrit, RBC indices (includes: mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], MCH concentration [MCHC]) and WBC differential count (includes: neutrophils, lymphocytes, monocytes, eosinophils and basophils)

    Measured: Up to Day 17

  6. Number of subjects with abnormal clinical biochemistry values

    Clinical chemistry includes: blood Urea Nitrogen (BUN), creatinine, Glucose (fasting), potassium, chloride, calcium, sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline phosphatase (ALP), total and direct bilirubin, uric acid, albumin and total protein

    Measured: Up to Day 17

  7. Number of subjects with abnormal urinalysis results

    Urinalysis includes: Specific gravity, analysis of pH, glucose, protein, blood \& ketones by dipstick method, and microscopic examination (if blood or protein is abnormal)

    Measured: Up to Day 17

Timeline

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

  1. First posted19 Jul 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionNov 2016
  4. Study completionNov 2016

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02837380
Sponsor's protocol ID
200558
Status last verified
Jan 2017
First submitted
15 Jul 2016
Last updated
25 Jan 2017
Results posted
No
Data monitoring committee
No

Publications

  • Li Y, Li H, Sheng Y, Du X, Yao Y, Luo X, Ma P. Pharmacokinetics of Single and Repeat Doses of Fluticasone Furoate/Umeclidinium/Vilanterol in Healthy Chinese Adults. Clin Pharmacol Drug Dev. 2019 Aug;8(6):721-733. doi: 10.1002/cpdd.626. Epub 2018 Nov 14.

    PubMed 30427594

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FF and VI/UMEC in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in China.

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 12 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 Jan 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 China. 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 concentration (Cmax) of FF, UMEC and VI after single inhaled dose on Day1 (time frame: Pre-dose, 5 minutes (min), 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1). The study lists 17 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 NCT02837380, 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 Jan 2017.

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