Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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