Efficacy and Safety of the Addition of Fluticanse Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide (62.5 or 125mcg) Once-daily Over 12 Weeks
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: Umeclidinium bromide 62.5mcg; Umeclidinium bromide 125mcg; Fluticasone propionate 250mcg/Salmeterol 50mcg; Placebo
Intervention description: Inhalation Powder, LAMA 62.5mcg; Inhalation Powder, LAMA 125mcg; Inhalation Powder, ICS/LABA; Inhalation Powder, Placebo
Intervention MeSH terms: Fluticasone; Xhance; Bromides; Salmeterol Xinafoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 617.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        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-childbearing potential, or if of child bearing potential, has a negative serum
             pregnancy test at screening, and agrees to one of the acceptable contraceptive methods
             listed in the protocol, used consistenty 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 the medications listed in the protocol
             according to protocol-specific times prio 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.