A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol With Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: UMEC/VI Inhalation Powder 62.5/25 mcg via NDPI; FSC Inhalation Powder 250/50 mcg via ACCUHALER/DISKUS; Placebo DISKUS; Placebo NDPI
Intervention description: The drug is administered via NDPI as one inhalation once daily in the morning. NDPI has two strips, each containing 30 blisters of medication. The first strip has UMEC blended with lactose and magnesium stearate in the form of dry white powder with a dosage of 62.5 mcg per blister and the second strip has VI blended with lactose and magnesium stearate in the form of dry white powder with a dosage of 25 mcg per blister.; The drug is administered via ACCUHALER/DISKUS inhaler as one inhalation each morning and evening. The inhaler contains a single strip with 60 blisters of medication. The strip has 250 mcg of fluticasone propionate and 50 mcg of salmeterol per blister in the form of dry white powder.; Placebo is administered via ACCUHALER/DISKUS inhaler as one inhalation each morning and evening. The inhaler contains 1 strip with 60 blisters of placebo in the form of dry white powder.; Placebo is administered via NDPI as one inhalation once daily in the morning. The inhaler contains 2 strips with 30 blisters of placebo per strip in the form of dry white powder.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 700.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: GSK573719; lung function; salmeterol (SAL); umeclidinium bromide (UMEC); GW642444; Chronic obstructive pulmonary disease; Novel Dry Powder Inhaler (NDPI); fluticasone propionate (FP); vilanterol (VI)

Summary:

      Umeclidinium/vilanterol (UMEC/VI) is a combination product under development that is used for
      the treatment of airflow obstruction in patients with COPD. Fluticasone propionate/salmeterol
      (FSC) is an approved drug that is already in use for the treatment of COPD. This is a
      multicenter, randomized, double-blind, double-dummy, parallel group study to evaluate the
      efficacy and safety of UMEC/VI 62.5/25 microgram [mcg] once daily administered via Novel Dry
      Powder Inhaler (NDPI) compared with fluticasone propionate /salmeterol (FSC) 250/50 mcg
      twice-daily when administered via ACCUHALER/DISKUS inhaler over a treatment period of 12
      weeks in subjects with COPD. Eligible subjects will be equally randomized to UMEC/VI 62.5/25
      mcg or FSC 250/50 mcg for 12 weeks. A safety follow-up assessment will be conducted
      approximately 7 days after the end of the study treatment.
    

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 in the
             study if she is of: Non-child bearing potential (i.e. physiologically incapable of
             becoming pregnant, including any female who is post-menopausal or surgically sterile).
             Or if of child bearing potential, has a negative pregnancy test at screening, and
             agrees to one of the acceptable contraceptive methods mentioned 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 as follows: COPD is a
             preventable and treatable disease state characterized by airflow limitation that is
             not fully reversible. The airflow limitation is usually progressive and is associated
             with an abnormal inflammatory response of the lungs to noxious particles or gases,
             primarily caused by cigarette smoking. Although COPD affects the lungs, it also
             produces significant systemic consequences.

          -  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)]. Previous 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-salbutamol FEV1/FVC ratio of <0.70 and a
             post-salbutamol FEV1 of >=30% and <=70% of predicted normal values calculated using
             National Health and Nutrition Examination Survey (NHANES) III reference equations at
             Visit 1.

          -  Dyspnea: A score of >=2 on the Modified Medical Research Council Dyspnea Scale (mMRC)
             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 alpha-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 condition in addition to COPD should be excluded. Examples may
             include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or
             interstitial lung disease. Inactive tuberculosis in more than one lobe is
             exclusionary. Allergic rhinitis is not exclusionary.

          -  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: A history of allergy or hypersensitivity to any
             anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid,
             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
             anticholinergic.

          -  Hospitalization: Hospitalization for pneumonia within 12 weeks prior to Visit 1.

          -  History of COPD Exacerbation: A documented history of at least one COPD exacerbation
             in the 12 months prior to Visit 1 that required either oral corticosteroids,
             antibiotics, and/or hospitalization. Prior use of antibiotics alone does not qualify
             as an exacerbation history unless the use was associated with treatment of worsening
             symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence.

          -  Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior
             to Screening (Visit 1).

          -  12-Lead electrocardiogram (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.

          -  Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period
             required prior to spirometry testing at each study visit.

          -  Medications Prior to Screening: Use of the following medications according to the
             following defined time intervals prior to Visit 1: Depot corticosteroids - 12 weeks,
             Systemic, oral or parenteral corticosteroids - 6 weeks, Antibiotics (for lower
             respiratory tract infection) - 6 weeks, Cytochrome P450 3A4 strong inhibitors - 6
             weeks, Herbal medications potentially containing oral or systemic steroids - 6 weeks,
             Inhaled corticosteroids (ICS) - 30 days, Long-acting beta2-agonist (LABA)/ICS
             combination products - 30 days, Phosphodiesterase 4 (PDE4) inhibitors (e.g.,
             roflumilast) - 14 days, Inhaled long-acting anticholinergics - 7 days, Olodaterol and
             Indacaterol - 10days, Theophyllines - 48 hours, Oral leukotriene inhibitors
             (zafirlukast, montelukast, zileuton) - 48 hours, Oral beta2-agonists Long-acting-48
             hours/Short-acting - 12 hours, Inhaled long acting beta2-agonists (LABA, e.g.,
             salmeterol, formoterol, indacaterol) - 48 hours, Inhaled sodium cromoglycate or
             nedocromil sodium - 24 hours, Inhaled short acting beta2-agonists - 4 hours, Inhaled
             short-acting anticholinergics - 4 hours, Inhaled short-acting
             anticholinergic/short-acting beta2-agonist combination products - 4 hours, Any other
             investigational medication - 30 days or within 5 drug half-lives (whichever is
             longer).

          -  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 ex-clusionary.

          -  Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use)
             of short-acting bronchodilators (e.g., 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,
             sub-investigator, study coordinator, or employee of the participating investigator.

          -  Inability to read: A subject will not be eligible for the study if in the opinion of
             the investigator the subject cannot read.