Determine the Safety and Efficacy of (R,R)-Formoterol in the Treatment of Subjects With COPD

• time-normalized area under the percent change from visit predose curve for FEV1 over 12 hours (nAUC0-12-P) [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• Peak percent of predicted FEV1 [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• time-normalized area under the percent change in FEV1 from study baseline over 12 hours (nAUC0-12-B) [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• time-normalized area under the percent change from visit predose curve for FEV1 over 24 hours (nAUC0-24-P) [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• time-normalized area under the percent change in FEV1 from study baseline curve over 24 hours (nAUC0-24-B) [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• peak percent change in FEV1 from visit predose and study baseline [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• time point changes in FEV1; time to onset of response [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• time to peak change in FEV1 [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• at-home and in-clinic peak expiratory flow rate (PEFR) [ Time Frame: Weeks -2, 0, 3, 6, 9, 12 ]
• relationship between the plasma concentration values and selected pharmacodynamic parameters [ Time Frame: Weeks -2, 0, 3, 6, 9, 12, 13 ]
• Supplemental ipratropium bromide MDI and racemic albuterol MDI use [ Time Frame: Weeks 0-13 ]
• COPD exacerbations and COPD symptom ratings [ Time Frame: Weeks 0-13 ]
• St. George's Hospital Respiratory Questionnaire [ Time Frame: Weeks 0, 6, 13 ]
• Investigator and Subject Global Evaluations [ Time Frame: Weeks -2, 12, 13 ]
• Baseline and Transitional Dyspnea Index [ Time Frame: Weeks -2, 6, 12 ]
• distance walked in six minutes [ Time Frame: Weeks -2, 3, 9 ]

• Chronic Obstructive Pulmonary Disease
• Chronic Bronchitis
• Emphysema

• Drug: arformoterol tartrate inhalation solution
  arformoterol 50 mcg QD
  Other Name: (R,R)-formoterol
• Drug: arformoterol tartrate inhalation solution
  arformoterol 25 mcg BID
  Other Name: (R,R)-formoterol
• Drug: arformoterol tartrate inhalation solution
  arformoterol 15 mcg BID
  Other Names:

  • (R,R)-formoterol
  • Brovana
• Drug: Salmeterol
  Salmeterol MDI 42 mcg BID
  Other Name: Serevent MDI
• Drug: Placebo
  Placebo BID

• Experimental: 1
  Arformoterol 50 mcg QD and placebo MDI
  Intervention: Drug: arformoterol tartrate inhalation solution
• Experimental: 2
  Arformoterol 25 mcg BID and Placebo MDI
  Intervention: Drug: arformoterol tartrate inhalation solution
• Experimental: 3
  Arformoterol 15 mcg BID and placebo MDI
  Intervention: Drug: arformoterol tartrate inhalation solution
• Active Comparator: 4
  Salmeterol MDI 42 mcg BID and placebo inhalation solution
  Intervention: Drug: Salmeterol
• Placebo Comparator: 5
  Placebo MDI and placebo inhalation solution
  Intervention: Drug: Placebo

Inclusion Criteria:

• Be willing to comply with study procedures and visit schedule
• Are at least 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: documented surgically sterile, OR postmenopausal.
• Have a primary diagnosis of COPD. 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).
• Have a chest x-ray that is consistent with the diagnosis of COPD and taken <3 months prior to study start
• Able to complete all study questionnaires and logs reliably

Exclusion Criteria:

• Female subject who is pregnant or lactating
• Have participated in an investigational drug study within 30 days prior to study start, or who is currently participating in another investigational drug study
• Subject whose schedule or travel prevents the completion of all required visits
• Are scheduled for in-patient hospitalization, including elective surgery during the trial
• Have life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days
• History of asthma or any chronic respiratory disease other than COPD (chronic bronchitis and/or emphysema)
• Have clinically significant cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol
• Have a history of cancer except non-melanomatous skin cancer
• Have a history of lung resection of more than one full lobe
• Requires continuous supplemental oxygen therapy.
• Has 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 arformoterol, ipratropium, salmeterol or albuterol or any of the excipients contained in any of these formulations
• Have a history of substance abuse or drug abuse within 12 months, or with a positive urine drug screen
• Are using any prescription drug for which concomitant beta-agonist administration is contraindicated (e.g., beta-blockers)