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 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.