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”

A 12 week study to investigate the safety and effectiveness of arformoterol given twice daily compared to placebo in subjects with COPD.

Study Type: Interventional

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

Study Primary Completion Date: June 2003

This study is a double-blind, double-dummy, randomized, placebo- and active-controlled, multicenter, parallel-group study of adult subjects with a primary clinical diagnosis of COPD. Approximately 800 subjects were to be randomized in this study. Study participation consisted of a total of eight (8) study visits over approximately four (4) months for each subject.

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 MDI
  • Salmeterol MDI 42 mcg BID
• Drug: Placebo
  • Placebo BID MDI

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Arformoterol 50 mcg QD and placebo MDI
• Experimental: B
  • Arformoterol 25 mcg BID and placebo MDI
• Experimental: C
  • Arformoterol 15 mcg BID and placebo MDI
• Active Comparator: D
  • Salmeterol MDI 42 mcg BID and placebo inhalation solution
• Placebo Comparator: E
  • Placebo BID MDI and inhalation solution

Primary Measures

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

Secondary Measures

• Time-normalized area under the percent change from visit pre-dose curve for FEV1 over 12 hours (nAUC0-12)
  • 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 from study baseline curve for FEV1 over 12 hours (nAUC0-12)
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: Yes
• Time-normalized area under the percent change from study baseline curve for FEV1 over 24 hours (nAUC0-24)
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• Timepoint changes in FEV1
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No
• 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, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    Safety Issue?: No
• Ipratropium bromide MDI use
  • Time Frame: Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    Safety Issue?: Yes
• Racemic albuterol MDI use
  • Time Frame: Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    Safety Issue?: Yes
• Exacerbations of COPD
  • Time Frame: Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    Safety Issue?: Yes
• COPD symptom ratings (over 12 weeks of treatment)
  • Time Frame: Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    Safety Issue?: No
• Relationship between plasma concentrations of (R,R) formoterol and selected pharmacodynamic parameters
  • Time Frame: Weeks -2, 0, 3, 6, 9, 12
    Safety Issue?: No

Inclusion Criteria

• Subject may be male or female and must be aged less than or equal to 35 years on the day the informed consent is signed.
• Female subjects greater than or equal to 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 (defined as status post-hysterectomy or bilateral tubal ligation) OR
• postmenopausal
• Subject must have a primary diagnosis of COPD, which may include components of chronic bronchitis and/or emphysema. Diagnosis can be made during the screening process.
• Subject must have a minimum smoking history of 15 pack-years (pack-years = the number of cigarette packs per day times the number of years).
• Subject must have a chest x-ray that is consistent with the diagnosis of COPD (e.g., not diagnostic of pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions) and taken less than or equal to 3 months prior to study start. If there is no chest x-ray taken less than or equal to 3 months prior to study start, or if recent results are unavailable for review, a chest x-ray will be performed.
• Subject must be able to complete all study questionnaires and logs reliably. Exclusion
• Criteria
• Female subject who is pregnant or lactating.
• Subject who has 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.
• 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 study start.
• Subject with a 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 history of cancer except non-melanomatous skin cancer. Subjects with a history of cancer that is considered surgically cured and without a recurrence within the past 10 years may participate in the study. History of hematologic/lymphatic malignancy treated with chemotherapy or radiation is not allowed.
• Subject with a history of lung resection of more than one full lobe.
• Subject who requires continuous supplemental oxygen therapy (unless subject resides at elevation greater than or equal to 4,000 feet).
• Subject who has had a change in dose or type of any medications for COPD within 14 days prior to the screening visit.
• Subject with a known sensitivity to (R,R)-formoterol, ipratropium, salmeterol or albuterol or any of the excipients contained in any of these formulations.
• Subject with a history of substance abuse or drug abuse within 12 months of study start, or with a positive urine drug screen at study start.
• Subject 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 August 21, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00685841

Study ID Number: 091-050

ClinicalTrials.gov Identifier: NCT00685841

Health Authority: United States: Food and Drug Administration