Efficacy and Safety of the Addition of Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide Inhalation Powder (62.5 or 125mcg) Once-daily Over 12 Weeks.



Status:Completed
Conditions:Chronic Obstructive Pulmonary Disease, Pulmonary
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:40 - Any
Updated:4/21/2016
Start Date:January 2013
End Date:August 2013

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A Multicenter, Randomized, Double-blind, Parallelgroup Study to Evaluate the Efficacy and Safety of the Addition of Umeclidinium Bromide Inhalation Powder (62.5mcg) Once-daily to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily, Umeclidinium Bromide Inhalation Powder (125mcg) Once-daily to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily Versus Placebo to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily Over 12 Weeks in Subjects With COPD.

The purpose of this 12 week study is to evaluate the effects of the addition of umeclidinium
bromide (62.5mcg) once-daily to fluticasone propionate (250/50mcg) twice-daily and
umeclidinium bromide (125mcg) once-daily to fluticasone propionate (250/50mcg) twice-daily
with placebo when added to fluticasone propionate (250/50mcg) twice-daily on lung function,
COPD-related health status assessments and safety in COPD subjects.

This is a multicenter, randomized, double-blind, parallel-group study. Subjects who meet the
eligibility criteria at screening and meet the randomization criteria at the end of a 4 week
run-in period will enter a 12 week treatment period. There will be a 7 day follow-up period
after the treatment period.

Inclusion Criteria:

- Type of subject: Outpatient.

- Informed Consent: A signed and dated written informed consent prior to study
participation.

- Age: Subjects 40 years of age or older at Visit 1.

- Gender: Male or female subjects. A female is eligible to enter and participate if of
non-child-bearing potential, or if of child bearing potential, has a megative serum
pregnancy test at screening, and agrees to one of the acceptable contraceptive
methods listed in the protocol, used consistently and correctly.

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

- Smoking History: Current or former cigarette smokers with a history of cigarette
smoking of ≥10 pack-years [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)]. Former smokers are defined as those who have stopped smoking
for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to
calculate pack year history.

- Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and
a pre and post-albuterol/salbutamol FEV1 of ≤70% of predicted normal values at Visit
1 (Screening) calculated using Nutrition Health and Examination Survey (NHANES) III
reference equations.

- Dyspnea: A score of ≥2 on the mMRC Dyspnea Scale at Visit 1.

Exclusion Criteria:

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

- Asthma: A current diagnosis of asthma.

- Other Respiratory Disorders: Known α-1 antitrypsin deficiency, active lung infections
(such as tuberculosis), and lung cancer are absolute exclusionary conditions. A
subject who, in the opinion of the investigator, has any other significant
respiratory conditions in addition to COPD should be excluded. Examples may include
clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or
interstitial lung disease.

- Other Diseases/Abnormalities: Subjects with historical or current evidence of
clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
immunological, endocrine (including uncontrolled diabetes or thyroid disease) or
hematological abnormalities that are uncontrolled and/or a previous history of cancer
in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has
been resected for cure is not exclusionary). 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.

- Contraindications: Any history of allergy or hypersensitivity to any
anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic,
corticosteroid (intranasal, inhaled or systemic) 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 study physician
contraindicates study participation or use of an inhaled anticholingeric.

- Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit
1.

- Lung Resection: Subjects with lung volume reduction surgery within the 12 months
prior to Visit 1.

- 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted
at Visit 1. Investigators will be provided with ECG reviews conducted by a
centralized independent cardiologist to assist in evaluation of subject eligibility.
Specific ECG findings that preclude subject eligibility are listed in Appendix 4. The
study investigator will determine the medical significance of any ECG abnormalities
not listed in Appendix 4.

- Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4
hour period required prior to spirometry testing at each study visit.

- Medications Prior to Screening: use of certain medications for the protocol-specific
times prior to Visit 1.

Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for
greater than 12 hours a day. As-needed oxygen use (i.e., ≤12 hours per day) is not
exclusionary.

- Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use)
of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.

- Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary
rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the
maintenance phase of a pulmonary rehabilitation program are not excluded.

- Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2
years prior to Visit 1.

- Affiliation with Investigator Site: A subject will not be eligible for this study if
he/she is an immediate family member of the participating investigator,
subinvestigator, study coordinator, or employee of the participating investigator.

- Inability to read: In the opinion of the investigator, any subject who is unable to
read and/or would not be able to complete a questionnaire.
We found this trial at
17
sites
Charlotte, North Carolina 28203
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Cincinnati, Ohio 45229
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Coeur d'Alene, Idaho 83814
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Concepción, Región Del Biobio 40700
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DeLand, Florida 32720
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Huntington Beach, California 92647
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Mobile, Alabama 36617
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Mobile, AL
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Newport News, Virginia 23606
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Newport News, VA
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Orlando, Florida 32806
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Phoenix, Arizona 85012
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Richmond, Virginia 23298
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Rock Hill, South Carolina 29732
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Seneca, South Carolina 29678
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Seneca, SC
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Spartanburg, South Carolina 29303
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St. Charles, Missouri 63301
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Sunset, Louisiana 70584
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Sunset, LA
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Tampa, Florida 33612
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Tampa, FL
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