To Evaluate the Long-term Safety of (R,R)-Formoterol in Subjects With COPD

INCLUSION CRITERIA: In order to qualify for participation, subjects must meet the following criteria:

• Must give written informed consent prior to participation. Women of childbearing potential must also sign the Women of Childbearing Potential Addendum.
• Must be willing to comply with study procedures and visit schedule
• Male or female >35 years of age
• Female subjects <65 years of age must have a serum pregnancy test conducted at Visit 1 and confirmed negative prior to randomization. Subjects of childbearing potential must be using an acceptable method of birth control.
• Female subjects who are considered not of childbearing potential must be: (1) documented surgically sterile, OR (2) postmenopausal
• Have a primary diagnosis of COPD, which may include components of chronic bronchitis and/or emphysema. Diagnosis can be made during the screening process.
• Have a minimum smoking history of 15 pack-years (pack-years = the number of cigarette packs per day times the number of years)
• Medical Research Council (MRC) Dyspnea Scale Score >2
• Have a baseline FEV1 <65% of predicted normal value and >0.70 L documented prior to randomization
• Have an FEV1/FVC ratio <70% documented prior to randomization.
• Have a chest x-ray that is consistent with the diagnosis of COPD and taken <3 months prior to Visit 1. If there is no chest x-ray taken 3 months prior to Visit 1, a chest x-ray will be performed prior to Visit 2.
• Be able to complete all study questionnaires and logs reliably

EXCLUSION CRITERIA: In order to qualify for participation, subjects must not meet any of the following criteria:

• Currently using disallowed medications or will be unable to complete the medication washout periods
• Female subject who is pregnant or lactating
• Have participated in an investigational drug study within 30 days prior to Visit 1 or who is currently participating in another investigational drug study
• Subject whose schedule or travel prevents the completion of all required visits
• Subject who is scheduled for in-patient hospitalization, including elective surgery (in-patient or out-patient) during the trial.
• Subject with life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to Visit 1
• Known history of asthma or any chronic respiratory disease (including a current history of sleep apnea) other than COPD (chronic bronchitis and/or emphysema).
• Subject with a blood eosinophil count >5%
• Subject with clinically significant cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol
• History of cancer except non-melanomatous skin cancer
• History of lung resection of more than one full lobe
• Subject who requires continuous supplemental oxygen therapy. The use of supplemental oxygen, not to exceed 2 L/minute, at nighttime only and/or only during exercise is allowed.
• Have had a change in dose or type of any medications for COPD within 14 days prior to the screening visit
• Have a known sensitivity to (R,R)-formoterol, ipratropium, salmeterol or albuterol or any of the excipients contained in any of these formulations
• Have clinically significant abnormalities that may interfere with the metabolism or excretion of the study drug
• Have a history of substance abuse or drug abuse within 12 months of Visit 1 or with a positive urine drug screen at the screening visit
• Subject with clinically significant abnormal laboratory values
• Subject with clinically significant abnormal 12-lead ECG that may jeopardize the subject's ability to complete the study
• Subject using any prescription drug for which concomitant beta-agonist administration is contraindicated