A Randomized, Double Blind, Placebo Controlled, Incomplete Block, Crossover, Dose Ranging Study to Evaluate the Dose Response of GSK573719 Administered Once or Twice Daily Over 7 Days in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: GSK573719; GSK573719; GSK573719; GSK573719; GSK573719; GSK573719; Tiotropium; Placebo
Intervention description: 125 mcg once daily; 62.5 mcg once daily; 31.25 mcg once daily; 15.6 mcg once daily; 31.25 mcg twice daily; 15.6 mcg twice daily; 18 mcg once daily; once or twice daily
Intervention MeSH terms: Tiotropium Bromide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 163.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Long acting muscarinic antagonist; Tiotropium; Chronic Bronchitis; Emphysema; Chronic Obstructive Pulmonary Disease

Summary:

      The purpose of this study is to further characterize the dose response of GSK573719 at doses
      of 15.6 micrograms (mcg) to 125 mcg once daily in patients with chronic obstructive pulmonary
      disease (COPD). Treatment with doses of GSK573719 dosed twice daily will also be included to
      further evaluate dosing frequency. Treatment with tiotropium (18 mcg) once daily via the
      Handihaler will be included as an active control. A placebo treatment will be included in
      order to evaluate absolute treatment effect of the different doses of GSK573719.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Outpatient

          -  A signed and dated written informed consent prior to study participation.

          -  Male or female adults.

          -  40 to 80 years of age at Visit 1

          -  Diagnosis of COPD

          -  Current or former cigarette smokers with a history of cigarette smoking of greater
             than or equal to 10 pack-years

          -  Post-albuterol forced expiratory volume in 1 second (FEV1)/ forced vital capacity
             (FVC)<0.70 and post albuterol FEV1 of greater than or equal to 35% and less than or
             equal to 70% of predicted normal values

        Exclusion Criteria:

          -  Women who are pregnant or lactating or are planning on becoming pregnant during the
             study.

          -  A current diagnosis of asthma

          -  Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis),
             and lung cancer

          -  Other significant respiratory conditions in addition to COPD

          -  Other diseases that are uncontrolled including cancer in remission for less than 5
             years

          -  Chest x-ray or CT scan with clinically significant abnormalities not believed to be
             due to the presence of COPD

          -  Hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist,
             lactose/milk protein or magnesium stearate

          -  A medical condition that contraindicates study participation or use of an inhaled
             anticholinergic

          -  Hospitalization for COPD or pneumonia within 12 weeks of Visit 1

          -  Any previous lung resection surgery

          -  A body mass index (BMI) value of >35 kilogram (kg)/meter squared (m2)

          -  An abnormal and significant electrocardiogram finding at Visit 1

          -  Significantly abnormal finding from clinical chemistry or haematology tests at Visit
             1.

          -  A positive Hepatitis B surface antigen or positive Hepatitis C antibody

          -  Medically unable to withhold albuterol (salbutamol) for the 6 hour period prior to
             study visits

          -  Use of depot corticosteroids within 12 weeks of Visit 1

          -  Use of oral or parenteral corticosteroids or antibiotics for lower respiratory tract
             infection within 6 weeks of Visit 1

          -  Use of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) product if
             LABA/ICS therapy is discontinued within 30 days of Visit 1

          -  Use of ICS at a dose of >1000mcg/day of fluticasone propionate or equivalent within 30
             days of Visit 1

          -  Initiation or discontinuation of ICS within 30 days of Visit 1

          -  Use of tiotropium or phosphodiesterase 4 inhibitors within 14 days of Visit 1

          -  Use of theophyllines, oral leukotriene inhibitors, long-acting oral beta-agonists, or
             inhaled long-acting beta-agonists within 48 hours of Visit 1

          -  Short-acting oral beta-agonists within 12 hours of Visit 1

          -  Use of LABA/ICS combination products only if discontinuing LABA therapy and switching
             to ICS monotherapy within 48 hours of Visit 1 for the LABA component

          -  Use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1

          -  Use of inhaled short-acting beta-agonists, inhaled short-acting anticholinergics, or
             inhaled short-acting anticholinergic/short-acting beta-agonist combination products
             within 6 hours of Visit 1

          -  Use of any other investigational medication within 30 days or 5 drug half-lives
             (whichever is longer)

          -  Oxygen therapy prescribed for greater than 12 hours a day

          -  Regular use (prescribed for use every day, not for as-needed use) of short-acting
             bronchodilators

          -  Use of continuous positive airway pressure (CPAP), nocturnal positive pressure or
             non-invasive positive pressure ventilation (NIPPV), including use for sleep apnea.

          -  Acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1

          -  A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1

          -  Anyone affiliated with investigator site

          -  Previous use of GSK573719 or GSK53719/GW642444