Efficacy Safety Study of Arformoterol QD Dosing Versus BID Dosing in COPD

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy and safety of arformoterol tartrate inhalation solution 30μg/4mL QD (two 15μg/2mL dosed in combination) over a 24-hour period compared to arformoterol tartrate inhalation solution 15μg/2 mL BID in subjects with COPD.

Detailed Description
-----------------
This is a modified blind, randomized, multicenter, single dose two-way crossover study to assess the efficacy and safety of arformoterol 15μg BID versus arformoterol 30μg QD in subjects with COPD. Subject participation will last approximately three weeks and will include a screening visit, two 24-hour visits, and a follow up telephone call. 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
-----------------
Modified-blind, Randomized, Multicenter, Single Dose, Two-way Crossover Study of Arformoterol Tartrate Inhalation Solution 15 Micrograms Twice A Day Versus 30 Micrograms Once A Day in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Arformoterol Tartrate Inhalation Solution
* Drug: Arformoterol Tartrate Inhalation Solution
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Subjects must have a FEV1/forced vital capacity (FVC) ratio of ≤ 70% at Visit 1. Exclusion Criteria: Subjects who do not have a 15 pack-year smoking history and a baseline breathlessness severity grade of 2 (as measured by the Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Screening. Subjects with life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to Visit

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15 mcg BID / 30 mcg QD<br>Arformoterol 15 microgram twice a day (BID) taken each morning and evening for one visit followed by Arformoterol 30 microgram once a day (QD) in the morning and placebo in the evening for the next visit. | Drug: Arformoterol Tartrate Inhalation Solution<br>* Nebulized arformoterol tartrate inhalation solution 15 microgram twice a day (BID)<br>* Other names: Brovana;Drug: Arformoterol Tartrate Inhalation Solution<br>* Nebulized arformoterol tartrate inhalation solution 30 microgram once a day (QD)<br>* Other names: Brovana;Drug: Placebo<br>* Placebo inhalation solution (citrate buffered 0.9% saline solution) once a day<br>|
| Experimental: 30 mcg QD / 15 mcg BID<br>Arformoterol 30 microgram once a day (QD) in the morning and placebo in the evening for one visit followed by Arformoterol 15 microgram twice a day (BID) in the morning and evening for the next visit. | Drug: Arformoterol Tartrate Inhalation Solution<br>* Nebulized arformoterol tartrate inhalation solution 15 microgram twice a day (BID)<br>* Other names: Brovana;Drug: Arformoterol Tartrate Inhalation Solution<br>* Nebulized arformoterol tartrate inhalation solution 30 microgram once a day (QD)<br>* Other names: Brovana;Drug: Placebo<br>* Placebo inhalation solution (citrate buffered 0.9% saline solution) once a day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 24 Hours | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken within 24 hours of dosing. | 0-24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 12 Hours | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken within 12 hours of dosing. | 0-12 hours | 
| Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Between 12-24 Hours | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken between 12 and 24 hours of dosing. | 12-24 hours | 
| Change in Forced Expiratory Volume in One Second From Pre-dose to the 24 Hour Time Point | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change in FEV1 from pre-dose to the readings taken 24 hours post-dose, which represents the trough in dose level. | pre-dose and 24 hours post-dose | 
| Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome offers the FEV1 readings taken pre-dose and at various time points within 24 hours post-dose. | pre-dose, immediately post-dose, 30 min, 1,2,4,6,8,10,12, 12.5,13,14,16,23,24 hours post first dose | 
| Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome offers the change in FEV1 readings between pre-dose and various time points within 24 hours post-dose. | Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose | 
| Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the percent of the estimated healthy lung function at specified time points. | Pre-dose, Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose | 
| Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the change in percent of the estimated healthy lung function at specified time points compared to the pre-dose value. | Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose | 
| Peak Percent of Predicted Forced Expiratory Volume at One Second (FEV1) Over 12 Hours Post-Dose. | Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the percent of the estimated healthy lung function and reports the highest percent found within 12 hours of dosing. | 12 hours | 
| Peak Change in Forced Expiratory Volume at One Second (FEV1) Within 12 Hours Post Dose Compared to Pre-dose | Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change in FEV1 from pre-dose to the readings taken 12 hours post-dose, and reports the largest change during that time. | 12 hours | 
| Time to Onset of 15 Percent Response Within 12 Hours of Dosing | Time to a 15 percent improvement in forced expiratory volume in one second (FEV1) within 12 hours of dosing. Only patients who achieved at least a 15 percent improvement are included. | 12 hours post first dose | 
| Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase Within 12 Hours of Dosing | Time to a 12 percent improvement in forced expiratory volume in one second (FEV1) AND a 200 milliliter increase in FEV1 within 12 hours of dosing. Only patients who met both conditions are included | up to 12 hours post dose | 
| Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase in Forced Expiratory Volume in One Second Within 12 Hours of Dosing | Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration. | pre-dose, immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose | 
| Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration. The measure compares the change from pre-dose reading to each post-dose time point. | immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, Chronic Bronchitis, Emphysema