An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444.Study B
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: GSK573719/GW642444 125/25; GSK573719/GW642444 62.5/25; GSK573719 125; GSK573719 62.5; GW642444 25; placebo
Intervention description: 125mcg/ 25mcg QID (Once daily , inhaled); 62.5mcg/25mcg QID; 125mcg QID; 62.5mcg QID; 25mcg QID; Comparator QID
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 307.0
Sex: Male
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      This is a phase III multicenter, randomized, double-blind, placebo-controlled, combination
      and component, two-period, incomplete block design cross-over study using GSK573719/GW642444.
      The primary objective is to evaluate lung function and exercise endurance time after 12 weeks
      of once-daily administration of GSK573719/GW642444 Inhalation Powder (125/25mcg and
      62.5/25mcg), GSK573719 Inhalation Powder (125mcg and 62.5mcg), GW642444 Inhalation Powder 25
      mcg and placebo delivered by a Novel dry powder inhaler (Novel DPI).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type of subject: Outpatient.

          -  Informed Consent: A signed and dated written informed consent prior to study
             participation.

          -  Age: 40 years of age or older at Visit 1.

          -  Gender: Male or female subjects.

          -  Diagnosis: An established clinical history of COPD in accordance with the definition
             by the American Thoracic Society/European Respiratory Society [Celli, 2004]

          -  Smoking History: Current or former cigarette smokers with a history of cigarette
             smoking of ≥ 10 pack-years

          -  Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of 0.70 and a
             post-albuterol/salbutamol FEV1 of >35% and <70% of predicted normal

          -  Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC)
             at Visit 1

          -  Resting Lung Volumes: A resting FRC of ≥120% of predicted normal FRC 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 respiratory disorders other than COPD including but
             not limited to alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis,
             sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease.
             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
             haematological 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. Any physical or mental abnormality
             which would affect the patient carrying out exercise tests including peripheral
             vascular disease should be excluded at the investigators discretion.

          -  Chest X-Ray: A chest X-ray or computed tomography (CT) scan that reveals evidence of
             clinically significant abnormalities not believed to be due to the presence of COPD. A
             chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available
             within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT
             scan) is not available in the 6 months prior to Visit 1 the subject will not be
             eligible for the study.

          -  Contraindications: A history of allergy or hypersensitivity to any
             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 study physician
             contraindicates study participation or use of an inhaled anticholinergic.

          -  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 Screening (Visit 1).

          -  12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at
             Visit 1, including the presence of a paced rhythm on a 12-lead electrocardiogram (ECG)
             which causes the underlying rhythm and ECG to be obscured. Investigators will be
             provided with ECG reviews conducted by a centralized independent cardiologist to
             assist in evaluation of subject eligibility.

          -  Screening Labs: Significantly abnormal finding from clinical chemistry and hematology
             tests at Visit 1.

          -  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, including depot,oral corticosteroids, combinations of
             LABA/ICS, LABA, PDE4 inhibitors.

          -  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: Is an investigator, sub-investigator, study
             coordinator, employee of a participating investigator or study site, or immediate
             family member of the aforementioned that is involved in this study