A Randomized Study, Comparing Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC /VI) Single Inhaler Triple Therapy, Versus Multiple Inhaler Therapy (Budesonide/Formoterol Plus Tiotropium) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)



Status:Active, not recruiting
Conditions:Chronic Obstructive Pulmonary Disease, Pulmonary
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:40 - Any
Updated:2/24/2019
Start Date:June 25, 2018
End Date:March 18, 2019

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A Phase IV, 12-week, Randomised, Double-blind, Triple Dummy Study to Compare Single Inhaler Triple Therapy, Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) With Multiple Inhaler Therapy (Budesonide/Formoterol Plus Tiotropium) Based on Lung Function and Symptoms in Participants With Chronic Obstructive Pulmonary Disease

The primary purpose of this study is to evaluate lung function and health related quality of
life (HRQoL) after 84 days of treatment with a single inhaler triple therapy combination of
FF/UMEC /VI [100/62.5/25 microgram (mcg)] once daily via ELLIPTA® compared with a multiple
inhaler combination therapy of Symbicort Metered Dose Inhaler (MDI) (budesonide/formoterol
320/9 mcg) twice daily plus Spiriva HandiHaler (tiotropium 18 mcg) once daily. The study will
inform healthcare providers that subjects can be effectively and safely switched to FF/UMEC
/VI single inhaler therapy from a multiple inhaler triple therapy regimen of Symbicort MDI
and Spiriva Handihaler. Eligible subjects will enter a 4-week run-in period during which they
will be administered budesonide/formoterol (320/9 mcg) twice daily plus tiotropium (18 mcg)
once daily plus placebo via ELLIPTA. Following the run-in period, subjects will be randomized
to receive one of the following study treatments for 84 days: 1) FF/UMEC /VI 100/62.5/25 mcg
via ELLIPTA once daily in the morning plus two inhalations of placebo to match
budesonide/formoterol via MDI, twice daily plus placebo to match tiotropium via HandiHaler
once daily in the morning or 2) Budesonide/formoterol 320/9 mcg via MDI, twice daily plus
tiotropium 18 mcg via HandiHaler once daily in the morning plus placebo via ELLIPTA once
daily in the morning. Subjects will then enter a one week follow-up period. The total
duration for a subject in the study will be approximately 17 weeks. ELLIPTA is a registered
trademark of the GlaxoSmithKline group of companies.


Inclusion Criteria:

- Subjects must be capable of giving signed informed consent prior to study start.

- Only outpatient subjects will be included

- Subjects (male or female) must be 40 years of age or older at Screening (Visit 1). A
female subject is eligible to participate if she is not pregnant, not breastfeeding,
and at least one of the following conditions applies: Not a woman of childbearing
potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during
the treatment period and until safety follow-up contact after the last dose of study
treatment

- An established clinical history of COPD in accordance with the definition by the
American Thoracic Society/European Respiratory Society

- Current or former cigarette smokers with a history of cigarette smoking of >=10
pack-years at Screening (Visit 1) [number of pack years = (number of cigarettes per
day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10
cigarettes per day for 20 years)]. Previous smokers are defined as those who have
stopped smoking for at least 6 months prior to Visit 1.

- Subjects with a score of >=10 on the COPD Assessment Test (CAT) at Screening (Visit 1)

- Subjects must demonstrate a post-bronchodilator FEV1 <50 % predicted normal or a
post-bronchodilator FEV1 <80 % predicted normal and a documented history of >=2
moderate exacerbations or one severe (hospitalized) exacerbation in the previous 12
months. Subjects must also have a measured post albuterol/salbutamol FEV1/forced vital
capacity (FVC) ratio of <0.70 at screening

- Subjects must have been receiving daily maintenance treatment for their COPD for at
least 3 months prior to Screening

Exclusion Criteria:

- Women who are pregnant or lactating or are planning on becoming pregnant during the
study

- Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma
are eligible if they have a current diagnosis of COPD).

- Subjects with alpha 1-antitrypsin deficiency as the underlying cause of COPD

- Subjects with active tuberculosis, lung cancer, and clinically significant:
bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung
disease or other active pulmonary diseases

- Subjects who have undergone lung volume reduction surgery within the 12 months prior
to Screening

- Immune suppression (e.g. advanced human immunodeficiency virus [HIV] with high viral
load and low cluster of differentiation 4 [CD4] count, lupus on immunosuppressants)
that in the opinion of the investigator would increase risk of pneumonia or other risk
factors for pneumonia (e.g. neurological disorders affecting control of the upper
airway, such as Parkinson's Disease, Myasthenia Gravis).

- Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least
14 days prior to Screening and at least 30 days following the last dose of oral or
systemic corticosteroids (if applicable)

- Respiratory tract infection that has not resolved at least 7 days prior to Screening

- Chest x-ray (posteroanterior and lateral) reveals evidence of pneumonia or a
clinically significant abnormality not believed to be due to the presence of COPD, or
another condition that would hinder the ability to detect an infiltrate on chest X-ray
(e.g. significant cardiomegaly, pleural effusion or scarring). All subjects will have
a chest X-ray at Screening Visit 1 (or historical radiograph or computerized
tomography [CT] scan obtained within 3 months prior to screening). For sites in
Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is
not available, approval to conduct a diagnostic chest x-ray will need to be obtained
from the Federal Office for Radiation Protection (BfS).

- Subjects with historical or current evidence of clinically significant cardiovascular,
neurological, psychiatric, renal, hepatic, immunological, gastrointestinal,
urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including
uncontrolled diabetes or thyroid disease) or hematological abnormalities that are
uncontrolled. Significant is defined as any disease that, in the opinion of the
Investigator, would put the safety of the subject at risk through participation, or
which would affect the efficacy or safety analysis if the disease/condition
exacerbated during the study.

- Unstable liver disease: alanine transaminase (ALT) >2 times Upper Limit of Normal
(ULN); and bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable
if bilirubin is fractionated and direct bilirubin <35 %). Current active liver or
biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones
or otherwise stable chronic liver disease per investigator assessment).

- Subjects with any of the following at Screening (Visit 1) would be excluded:
Myocardial infarction or unstable angina in the last 6 months; Unstable or life
threatening cardiac arrhythmia requiring intervention in the last 3 months; New York
Heart Association (NYHA) Class IV Heart failure.

- Abnormal and clinically significant 12-lead electrocardiogram (ECG) finding at Visit
1. The Investigator will determine the clinical significance of each abnormal ECG
finding in relation to the subject's medical history and exclude subjects who would be
at undue risk by participating in the trial. An abnormal and clinically significant
finding that would preclude a subject from entering the trial is defined as a 12-lead
ECG tracing that is interpreted at, but not limited to, any of the following: i)
Atrial Fibrillation (AF) with rapid ventricular rate >120 beats per minute (BPM); ii)
Sustained and non-sustained Ventricular tachycardia (VT); iii). Second degree heart
block Mobitz type II and third degree heart block (unless pacemaker or defibrillator
had been inserted); iv) QT interval corrected for heart rate by Fridericia's formula
(QTcF) >=500 milliseconds (msec) in subjects with QRS <120 msec and QTcF >=530 msec in
subjects with QRS >=120 msec.

- A history of allergy or hypersensitivity to any corticosteroid,
anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or
magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic
hypertrophy or bladder neck obstruction that, in the opinion of the Investigator,
contraindicates study participation.

- Subjects with carcinoma that has not been in complete remission for at least 3 years.
Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and
basal cell carcinoma of the skin would not be excluded based on the 3 year waiting
period if the subject has been considered cured by treatment.

- Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy >3 liters
per minute (L/min) at screening (Oxygen use <=3 L/min flow is not exclusionary)

- Subjects who are medically unable to withhold their albuterol/salbutamol for the
4-hour period required prior to spirometry testing at each study visit

- Subjects who have participated in the acute phase of a Pulmonary Rehabilitation
Programme within 4 weeks prior to screening or subjects who plan to enter the acute
phase of a Pulmonary Rehabilitation Program during the study. Subjects who are in the
maintenance phase of a Pulmonary Rehabilitation Program are not excluded.

- Subjects with a known or suspected history of alcohol or drug abuse within the last 2
years

- Subjects at risk of non-compliance, or unable to comply with the study procedures. Any
infirmity, disability, or geographic location that would limit compliance for
scheduled visits

- Subjects with a history of psychiatric disease, intellectual deficiency, poor
motivation or other conditions that will limit the validity of informed consent to
participate in the study

- Study Investigators, sub-Investigators, coordinators, employees of a participating
Investigator or study site, or immediate family members of the aforementioned that is
involved with this study

- In the opinion of the Investigator, any subject who is unable to read and/or would not
be able to complete study related materials

- Use of various medication prior to screening.
We found this trial at
38
sites
Saint Louis, Missouri 63110
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Bakersfield, California 93309
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Boerne, Texas 78006
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Breclav, 69002
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Celebration, Florida 34747
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Charlotte, North Carolina 28203
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Cincinnati, Ohio 45229
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Clearwater, Florida 33759
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Clinton, South Carolina 29325
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Doral, Florida 33172
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Duluth, Georgia 30096
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Evanston, Illinois 60201
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Evansville, Indiana 47714
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Farmington Hills, Michigan 48334
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Greenville, South Carolina 29615
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Hialeah, Florida 33013
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Jefferson Hills, Pennsylvania 15025
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Leesburg, Florida 34748
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Longwood, Florida 32779
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McKinney, Texas 75071
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Miami, Florida 33136
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Mobile, Alabama 36617
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Mount Pleasant, South Carolina 29464
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Richmond, Virginia 23298
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Rincon, Georgia 31326
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Rochester, Michigan 48307
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Sacramento, California 95815
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San Antonio, Texas 78258
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San Diego, California 92111
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Sebring, Florida 33870
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Spartanburg, South Carolina 29303
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Tacoma, Washington 98405
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Tullahoma, Tennessee 37388
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Union, South Carolina 29379
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Westminster, California 92683
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Winter Park, Florida 32789
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