Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
The purpose of this study is to evaluate the efficacy and safety of GSK233705B compared with
 placebo in subjects with 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.