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

Study Overview
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Brief Summary
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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

Detailed Description
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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. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Official Title
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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

Conditions
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Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, Emphysema

Intervention / Treatment
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* Drug: arformoterol tartrate inhalation solution
* Drug: arformoterol tartrate inhalation solution
* Drug: arformoterol tartrate inhalation solution
* Drug: Salmeterol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Arformoterol 50 mcg QD and placebo MDI | Drug: arformoterol tartrate inhalation solution<br>* arformoterol 50 mcg QD<br>* Other names: (R,R)-formoterol;|
| Experimental: 2<br>Arformoterol 25 mcg BID and Placebo MDI | Drug: arformoterol tartrate inhalation solution<br>* arformoterol 25 mcg BID<br>* Other names: (R,R)-formoterol;|
| Experimental: 3<br>Arformoterol 15 mcg BID and placebo MDI | Drug: arformoterol tartrate inhalation solution<br>* arformoterol 15 mcg BID<br>* Other names: Brovana;|
| Active Comparator: 4<br>Salmeterol MDI 42 mcg BID and placebo inhalation solution | Drug: Salmeterol<br>* Salmeterol MDI 42 mcg BID<br>* Other names: Serevent MDI;|
| Placebo Comparator: 5<br>Placebo MDI and placebo inhalation solution | Drug: Placebo<br>* Placebo BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Weeks -2, 0, 3, 6, 9, 12 | 

Secondary Outcome Measures

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