Official Title: “A Double-Blind, Double-Dummy, Randomized, Placebo- and Active-Controlled, Multicenter, Parallel-Group Study of (R,R)-Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease”

The purpose of this study is to assess the bronchodilator effect and safety of multiple daily doses of arformoterol administered for 12 weeks as maintenance treatment in patients with COPD

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: March 2004

This was a double-blind, double-dummy, randomized, placebo- and active-controlled, multicenter, parallel-group study of adult subjects with COPD. The study was double blinded through the use of both unit dose vial (UDV) and metered-dose inhaler (MDI) placebos, as appropriate. The primary efficacy analysis utilized the placebo control. Secondary analyses of the primary efficacy endpoint utilized the active control, and included comparisons between the placebo and active control.

Intervention(s) in this Clinical Trial

• Drug: arformoterol tartrate inhalation solution
  • arformoterol 50 mcg QD
• Drug: arformoterol tartrate inhalation solution
  • arformoterol 25 mcg BID
• Drug: arformoterol tartrate inhalation solution
  • arformoterol 15 mcg BID
• Drug: Salmeterol
  • Salmeterol MDI 42 mcg BID
• Drug: Placebo
  • Placebo BID

Arms, Groups and Cohorts in this Clinical Trial

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

Primary Measures

• percent change in trough FEV1 from study baseline to the end of the dosing interval (12 hours post-second dose for the BID treatment arms and 24 hours postdose for the QD treatment arm) over the double-blind period.
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No

Secondary Measures

• 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
    Safety Issue?: No
• Peak percent of predicted FEV1
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• peak percent change in FEV1 from visit predose and study baseline
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• time point changes in FEV1; time to onset of response
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• time to peak change in FEV1
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• at-home and in-clinic peak expiratory flow rate (PEFR)
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• relationship between the plasma concentration values and selected pharmacodynamic parameters
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12, 13
    Safety Issue?: No
• Supplemental ipratropium bromide MDI and racemic albuterol MDI use
  • Time Frame: Weeks 0-13
    Safety Issue?: No
• COPD exacerbations and COPD symptom ratings
  • Time Frame: Weeks 0-13
    Safety Issue?: Yes
• St. George's Hospital Respiratory Questionnaire
  • Time Frame: Weeks 0, 6, 13
    Safety Issue?: Yes
• Investigator and Subject Global Evaluations
  • Time Frame: Weeks -2, 12, 13
    Safety Issue?: Yes
• Baseline and Transitional Dyspnea Index
  • Time Frame: Weeks -2, 6, 12
    Safety Issue?: Yes
• distance walked in six minutes
  • Time Frame: Weeks -2, 3, 9
    Safety Issue?: Yes

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sepracor, Inc.

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00064402

Study ID Number: 091-051

ClinicalTrials.gov Identifier: NCT00064402

Health Authority: United States: Food and Drug Administration