Safety and Efficacy of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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To evaluate the long-term safety and monitor the long-term efficacy of arformoterol over a period of 6 months in subjects with chronic obstructive pulmonary disease (COPD).

Detailed Description
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This is a double-blind, double-dummy, multicenter, randomized, active-controlled, parallel group, outpatient, safety study to evaluate the long term safety of arformoterol in the treatment of subjects with COPD. Study participation will be over approximately 6 months. 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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Multicenter, Double-Blind, Double-Dummy, Randomized, Active-Controlled, Parallel Group Long-Term Safety Study of 15 μg and 25 μg Arformoterol Tartrate Inhalation Solution BID in Subjects With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease, Bronchitis, Emphysema

Intervention / Treatment
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* Drug: Arformoterol tartrate inhalation solution
* Drug: Arformoterol 25 ųg BID
* Drug: Formoterol 12 ųg BID
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female subjects must be at least 35 years old at the time of consent Subjects must have a pre-established, documented primary clinical diagnosis of non-asthmatic COPD or are referred for diagnosis of non-asthmatic COPD Subjects must have a >=15 pack-year smoking history and a baseline breathlessness severity grade of >=2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visits 1 and 2 Female subjects <=65 years of age must have a negative serum pregnancy test, females of childbearing potential must be using an acceptable method of birth control Subjects must be in general good health. Key Exclusion criteria: Subjects with a history of asthma, with the exception of asthma diagnosed in childhood Subjects with a blood eosinophil count >5% of total white blood cell count Subjects have had a febrile illness within 72 hours (3 days) before Screening Visit 1 Subjects with a chest x-ray that suggests a diagnosis other than COPD (e.g., diagnostic of pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions)

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 |
| --- | --- |
| Active Comparator: Formoterol 12 ųg 2x/day<br> | Drug: Formoterol 12 ųg BID<br>* Formoterol fumarate 12 ųg BID via aerolizer/DPI<br>* Other names: R,S-formoterol;Drug: Placebo<br>* Placebo nebule or placebo aerolizer<br>|
| Experimental: Arformoterol 15 ųg 2x/day<br> | Drug: Arformoterol tartrate inhalation solution<br>* Arformoterol 15 ųg BID by nebulization<br>* Other names: Brovana®;Drug: Placebo<br>* Placebo nebule or placebo aerolizer<br>|
| Experimental: Arformoterol 25 ųg 2x/day<br> | Drug: Arformoterol 25 ųg BID<br>* Arformoterol 25 ųg BID by nebulization<br>* Other names: R,R formoterol;Drug: Placebo<br>* Placebo nebule or placebo aerolizer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations | Percent of participants with the adverse event specified. SOC = system organ class. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With New 24-Hour Holter Monitoring Alerts | New holter monitoring alerts are defined as those alerts that occurred post-randomization and were not present at baseline. | Visit 6 (week 27) | 
| Number of Participants With Potentially Clinically Significant Glucose Evaluations | Patients with glucose values that met low (<=40 mg/dL) or high (>=175 mg/dL) criteria were considered potentially clinically significant. | visit 6 (week 27) | 
| Number of Participants With Potentially Clinically Significant Potassium Evaluations | Patients with potassium values that met low (<=3 mEq/L) or high (>=6 mEq/L) criteria were considered potentially clinically significant. | visit 6 (week 27) | 
| Number of Participants With New 12-Lead Electrocardiogram (ECG) Alerts | New Electrocardiogram (ECG) alerts are defined as those alerts that occurred post-treatment and were not present at baseline. | visit 6 (week 27) | 
| Inspiratory Capacity Changes From Baseline | Mean Change in Inspiratory Capacity values from baseline (baseline assessment obtained at Visit 2, pre-dose). Spirometry measurements collected within 6 hours following in-clinic rescue/supplemental medications use were excluded from analysis. | weeks 0,3,13,26 | 
| 6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) | The 6 hour peak change from baseline is the maximum of the post-dose change values through 6 hours at each visit. | weeks 0,3,13,26 | 
| Number of Participants With Potentially Clinically Significant Heart Rate | Number of subjects with a heart rate that was lower/higher than a set limit and increased/decreased from set baseline limit in beats per minute (bpm) | visit 6 (week 27) | 
| Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Days Used Per Week | Supplemental medication usage is recorded throughout the study. MDI stands for metered dose inhaler. | Screening (day-14 to 0) and Treatment (week 0 - 26) | 
| Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day | Supplemental medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication. | Screening (day-14 to 0) and Treatment (week 0 - 26) | 
| Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Days Used Per Week | Rescue medication usage during the study. MDI stands for metered dose inhaler. | Screening (day-14 to 0) and Treatment (week 0 - 26) | 
| Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day | Rescue medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication. | Screening (day-14 to 0) and Treatment (week 0 - 26) | 
| Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline | Area under the change from baseline curve from 0 to 6 hours. Time-normalized AUC (0-6 hrs) was derived using the linear trapezoidal method. | weeks 0,3,13,26 | 
| Transitional (Relative Change in) Dyspnea Index | The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A Transitional Dyspnea Index score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests. | weeks 13, 26 | 
| Number of Participants With an Improved Transitional Dyspnea Index | The number of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score compares current health against baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement. | weeks 13, 26 | 
| Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) | The 24 hour trough is the FEV1 value obtained 24 hours post first dose. This value is compared to the baseline FEV1 value. | weeks 0,3,13,26 | 
| Subject Global Evaluations Change From Baseline | The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1=much better and 7=much worse. Ratings were assessed relative to the subject's initial entry into the study. | weeks 13, 26 | 
| Investigator Global Evaluations Change From Baseline | The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. Ratings were assessed relative to the subject's initial entry into the study. | weeks 13, 26 | 
| BODE Index | The BODE index (0=relative health and 10=severe chronic obstructive pulmonary disease) is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the 6-minute walk test. Scores were derived using pre-dose assessments from each visit. | Baseline (visit 2), weeks 13, 26 | 
| 6-Minute Walk: Change From Baseline in the Distance Walked in 6 Minutes | Mean change from baseline in distance walked (meters) | Post-Dose weeks 0, 13, 26 | 
| Mean Change From Baseline in St. George's Respiratory Questionnaire | Scores are expressed as a mean change from baseline of overall impairment (total score). The questionnaire has a scale of 100 which represents worst possible health status to 0 which indicates best possible health status. | weeks 13, 26 | 
| Number of Participants With a >=4 Unit Improvement on the St. George's Respiratory Questionnaire | Scores are expressed as the number of participants with >= 4 unit improvement in overall impairment (total score), where 100 represents worst possible health status and 0 indicates best possible health status. | Visit 4 (week 13) , Visit 5 (week 26) | 
| Modified Medical Research Council Dyspnea Questionaire | Scores range from 0 to 4, with a score of 4 indicating that a subject is too breathless to leave the house or becomes breathless when dressing or undressing. The highest numbered question to which the subject answered 'Yes' is the Dyspnea Scale Score. | Baseline (visit 2), weeks 13, 26 | 
| Percent (%) of Participants With an Improved Transitional Dyspnea Index | The percentage of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score is the sum of the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement. | visits 4 (week 13), visit 5 (week 26) | 
| Percent (%) of Participants With a >=4 Unit Improvement in the St. George's Respiratory Questionaire | Percent of participants with a >=4 unit improvement in the overall impairment (total score) of the St. George's Respiratory Questionaire. This questionaire uses a 100 - 0 scale, where 100 represents the worst possible health status and 0 indicates the best possible health status. | visit 4 (week 13), visit 5 (week 26) | 
| Mean Values for the 6-Minute Walk Test: Distance Walked in Meters | This test measures the participants' level of fitness. It is a measure of the distance the participant can walk in 6 minutes. | Baseline (Visit 2), week 13, week 26 | 
| Mean Values for Investigator Global Evaluations | The investigator global evaluation is reported by the study investigator. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. | Baseline (Visit 2), Weeks 13, 26 | 
| Mean Values for St. George's Respiratory Questionnaire | A questionnaire to assess respiratory health. Scores are expressed as a percentage of overall impairment (total score), where 100 represents the worst possible health status and 0 indicates best possible health status. | Baseline (Visit 2), weeks 13, 26 | 
| Mean Values for Subject Global Evaluations | The subject global evaluation is reported by study subjects/participants. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. | Baseline (Visit 2), weeks 13, 26 | 
| Mean Values for Inspiratory Capacity | Inspiratory capacity is the maximum volume that can be inhaled. | Baseline (Visit 2), Weeks 3, 13, 26 | 
| Mean Values for Forced Expiratory Volume in One Second (FEV1) | Forced Expiratory Volume in one second | Baseline (Visit 2), weeks 3, 13, 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, chronic bronchitis, emphysema