Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate and compare the efficacy of arformoterol twice a day and tiotropium once a day (dosed sequentially) versus tiotropium once a day alone in subjects with Chronic Obstructive Pulmonary Disease (COPD).

Detailed Description
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This study is a multicenter, randomized, modified-blind, double-dummy two-week parallel-group efficacy and safety study of arformoterol tartrate inhalation solution twice daily, tiotropium inhalation powder once daily and arformoterol tartrate inhalation solution twice daily and tiotropium inhalation powder once daily (dosed sequentially) 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 Two-Week, Randomized, Modified-Blind, Double-Dummy, Parallel-Group Efficacy and Safety Study of Arformoterol Tartrate Inhalation Solution Twice-Daily, Tiotropium Once-Daily, and Arformoterol Tartrate Inhalation Solution Twice-Daily and Tiotropium Once Daily 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: Tiotropium
* Drug: Arformoterol and Tiotropium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects must be at least 45 years old at the time of consent. Subjects must have a pre-established primary clinical diagnosis of COPD. Subjects must have a baseline FEV1 of ≤65% of predicted normal value at Visit 1. Subjects must have a FEV1 ≥ 0.70L at Visit 1. Exclusion Criteria: Subjects who do not have a FEV1/forced vital capacity (FVC) ratio of ≤70% at Visit 1. Subjects who do not have a ³15 pack-year smoking history and a baseline breathlessness severity grade of ³2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visit 1.

Ages Eligible for Study
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Minimum Age: 45 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: Arformoterol 15 mcg twice daily<br>Arformoterol 15 mcg twice daily/Placebo Inhalation Powder | Drug: Arformoterol Tartrate Inhalation Solution<br>* Arformoterol tartrate inhalation solution 15 mcg twice daily and placebo inhalation powder once daily.<br>* Other names: Brovana®;Drug: Placebo<br>* Placebo inhalation solution and placebo inhalation powder<br>|
| Active Comparator: Tiotropium 18 mcg once daily<br>Tiotropium 18 mcg once daily/Placebo Inhalation Solution | Drug: Tiotropium<br>* Placebo inhalation solution twice daily and tiotropium inhalation powder 18 mcg once daily.<br>* Other names: Spiriva;Drug: Placebo<br>* Placebo inhalation solution and placebo inhalation powder<br>|
| Experimental: Arformoterol /Tiotropium<br>Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily | Drug: Arformoterol and Tiotropium<br>* Arformoterol tartrate inhalation solution 15 mcg twice daily and Tiotropium inhalation powder 18 mcg once daily.<br>* Other names: Spiriva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B) |  | 24 hours following two weeks of dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B) |  | 0-12 hours following two weeks of dosing | 
| Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B) |  | Following 2 weeks of dosing | 
| Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough) | Trough FEV1 is defined as the measurement collected approximately 24 hours after the first in-clinic double-blind dose at Week 0. Change is calculated as Week 2 24 hour post first dose FEV1 - Week 0 pre-first dose FEV1. | Following 2 weeks of dosing | 
| Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Baseline is FEV1 measurement collected prior to the first double-blind dose at week 0. Change defined as Week 0 FEV1 - Week 2 pre first dose FEV1. | 2 weeks | 
| Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Baseline is FEV1 collected prior to first double-blind dose at week 0. Change is defined as Week 0 FEV1 percent predicted - Week 2 pre first dose FEV1 percent predicted. | 2 weeks | 
| Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | 12 hour peak change in FEV1 is defined as maximum of the post dose changes through the nominal 12 hour assessment. | 2 weeks | 
| Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks | Analyzed from end of dosing to 12 hours. | 2 weeks | 
| Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks | Analyzed from end of dosing to 12 hours. | 2 weeks | 
| Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing | Trough Inspiratory Capacity is defined as the measurement collected approximately 24 hours after the first in clinic double-blind treatment dose at week 0. Change is calculated as Week 2 24 hr post dose IC - Week 0 pre first dose IC. | 2 weeks | 
| Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint |  | 2 Weeks | 
| Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Overall: Average of the levalbuterol usage in days per week over the 2 week period. Mean number of days/week=number of days levalbuterol used during time period, divided by number of days in the period, multiplied by 7. An actuation is one puff of levalbuterol. | 2 weeks | 
| Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Overall: Average of the usage in number of actuations per day over the 2 week period. An actuation is one puff of levalbuterol. Mean number of actuations/day=number actuations used during time period, divided by number of days in time period. | 2 weeks | 
| Transition Dyspnea Index (TDI) Focal Score | TDI Focal score (range -9 to 9) is defined as the sum of function impairment, magnitude of task, and magnitude of effort (each on a -3 to 3 scale). A score of -9 is maximum worsening and 9 is maximum improvement. | 2 weeks | 
| Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score | A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. | 2 weeks | 
| Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score | A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. | 2 weeks | 

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