Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: GSK233705 12.5mcg; GSK233705 25mcg; GSK233705 50mcg; GSK233705 100mcg; GSK233705 200mcg; Placebo
Intervention description: Once daily via dry powder inhaler; once daily via dry powder inhaler; Once daily via dry powder inhaler; Once daily via dry powder inhaler; Once daily via dry powder inhaler; Once daily via dry powder imhaler
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 576.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COPD; Multicenter; GSK233705B; double-blind; Chronic Obstructive Pulmonary Disease (COPD); randomized

Summary:

      The purpose of this study is to evaluate the efficacy and safety of GSK233705B compared with
      placebo in subjects with COPD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A signed and dated written informed consent prior to study participation.

          -  Male or female adults.

        A female is eligible to enter and participate in this study if she is of:

        non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
        including any female who is post-menopausal; or child-bearing potential, has a negative
        pregnancy test at Visit 1/Visit 1A, and agrees to one of the protocol-specified acceptable
        contraceptive methods used consistently and correctly (i.e. according to the approved
        product label and the instructions of the physician for the duration of the study -
        Screening through follow-up contact)

          -  40 to 80 years of age at Visit 1

          -  An established clinical history of COPD

          -  Current or previous cigarette smokers with a history of cigarette smoking of ≥ 10
             pack-years 1.

          -  A post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 and a post-albuterol/salbutamol
             FEV1 of ≥35 and ≤70% of predicted normal values

        Exclusion Criteria:

        Subjects meeting any of the following criteria must not be enrolled in the study:

          -  Women who are pregnant or lactating.

          -  A current diagnosis of asthma.

          -  Known respiratory disorders other than COPD including but not limited to α-1
             antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung
             cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and
             interstitial lung disease.

          -  Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy)

          -  Clinically significant Chest X-ray or computed tomography (CT) scan abnormalities
             within 6 months prior to Visit 1 that are not believed to be due to COPD.

          -  Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1.

          -  Hospitalization for COPD or pneumonia within 3 months prior to Visit 1.

          -  Use of antibiotics for a lower respiratory tract infection within 30 days prior to
             Visit 1.

          -  Clinically significant and uncontrolled cardiovascular, neurological, psychiatric,
             renal, gastro-intestinal, immunological, endocrine (including uncontrolled diabetes or
             thyroid disease) or hematological abnormalities.

          -  An abnormal and clinically significant 12-lead electrocardiogram (ECG) that results in
             active medical problem.

          -  Positive for Hepatitis B or Hepatitis C at Visit 1.

          -  A current malignancy or previous history of cancer in remission for <5 years prior to
             Visit 1

          -  A history of allergy or hypersensitivity to ipratropium, tiotropium, or atropine and
             any of their derivatives, lactose/milk protein or magnesium stearate.

          -  Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck
             obstruction that in the opinion of the study investigator would prevent use of an
             inhaled anticholingeric.

          -  Medically unable to withhold albuterol/salbutamol for 6 hours prior to spirometry
             testing at each study visit or to withhold ipratropium (if applicable) for the 6-hour
             period prior to the first 3 study visits (ipratropium cannot be used after Visit 3).

          -  Additional Medications: Unable to stop using certain medications such as
             bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1
             (the Investigator will discuss the specific medications)

          -  Use of inhaled corticosteroids at a dose greater than 1000 mcg/day of fluticasone
             propionate or equivalent within 30 days prior to Visit 1.

          -  Use of long-term oxygen therapy (LTOT) or supplemental oxygen required for greater
             than 12 hours a day. Oxygen use as needed is not exclusionary.

          -  Clinically significant sleep apnea that requires continuous positive airway pressure
             (CPAP)

          -  Use of regular nebulized therapy

          -  Use of nocturnal positive pressure or non-invasive positive pressure ventilation
             (NIPPV)

          -  Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks
             prior to Visit 1.

          -  An investigator, sub-investigator, study coordinator, employee of a participating
             investigator or study site, or immediate family member of the above who is involved in
             this study

          -  History of psychiatric disease, intellectual deficiency, poor motivation, substance
             abuse in the two years prior to Visit 1 (including drug and alcohol), or other
             conditions, which will limit the validity of informed consent to participate in the
             study.

          -  Use of GSK233705B in previous studies.