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

Study Overview
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Brief Summary
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The purpose of this study is to determine the long-term safety of arformoterol over a period of 12 months in subjects with COPD

Detailed Description
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This was a multicenter, open-label, randomized, active controlled, parallel group chronic safety study of arformoterol 50 mcg once daily over a period of 12 months in subjects with COPD. 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 Multicenter, Open-Label, Randomized, Active-Controlled, Parallel Group Chronic Safety 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
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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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

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Arformoterol tartrate 50 mcg QD | Drug: arformoterol<br>* Arformoterol inhalation solution, 50 mcg QD<br>* Other names: (R,R)-Formoterol;|
| Active Comparator: 2<br>Salmeterol 42 mcg BID | Drug: Salmeterol<br>* Salmeterol MDI, 42 mcg BID<br>* Other names: racemic formoterol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall occurrence of adverse events |  | Weeks -1, 0, 3, 6, 9, 13, 26, 39, 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory parameters |  | Weeks -1, 0, 3, 6, 9, 13, 26, 39, 52 | 
| ECG parameters |  | Weeks -1, 0, 3, 6, 9, 13, 26, 39, 52 | 
| 24-hour holter monitoring parameters |  | Weeks -1, 0, 13, 26, 39, 52 | 
| Vital signs |  | Weeks -1, 0, 3, 6, 9, 13, 26, 39, 52 | 
| Plasma arformoterol concentrations |  | Weeks -1, 0, 3, 6, 9, 13, 26, 39, 52 | 
| Physical examination findings |  | Weeks -1, 53 |