Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Chronic Bronchitis, Emphysema
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.
Interventions
Nebulized arformoterol tartrate inhalation solution 15 microgram twice a day (BID)
DRUGPlacebo
Placebo inhalation solution (citrate buffered 0.9% saline solution) once a day
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 24 Hours | 0-24 hours 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 measures the change from pre-dose for a series of FEV1 readings taken within 24 hours of dosing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Between 12-24 Hours | 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. |
| Change in Forced Expiratory Volume in One Second From Pre-dose to the 24 Hour Time Point | pre-dose and 24 hours 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 measures the change in FEV1 from pre-dose to the readings taken 24 hours post-dose, which represents the trough in dose level. |
| Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point 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 | 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. |
| Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point 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 | 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. |
| Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 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 | 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. |
| Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to 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 | 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. |
| Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 12 Hours | 0-12 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. |
| Peak Change in Forced Expiratory Volume at One Second (FEV1) Within 12 Hours Post Dose Compared to Pre-dose | 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 in FEV1 from pre-dose to the readings taken 12 hours post-dose, and reports the largest change during that time. |
| Time to Onset of 15 Percent Response Within 12 Hours of Dosing | 12 hours post first dose | 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. |
| Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase Within 12 Hours of Dosing | up to 12 hours post dose | 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 |
| 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 | 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 | Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration. |
| Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed 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 | 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. |
| Peak Percent of Predicted Forced Expiratory Volume at One Second (FEV1) Over 12 Hours Post-Dose. | 12 hours | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 15 Mcg BID / 30 Mcg QD Arformoterol 15 mcg twice a day (morning and evening) for one visit followed by Arformoterol 30 mcg once a day (morning) and placebo (evening) for the next visit. | 15 |
| 30 Mcg QD / 15 Mcg BID Arformoterol 30 mcg once a day (morning) and placebo (evening) for one visit followed by Arformoterol 15 mcg twice a day (morning and evening) for the next visit. | 18 |
| Total | 33 |
Baseline characteristics
| Characteristic | 15 Mcg BID / 30 Mcg QD | 30 Mcg QD / 15 Mcg BID | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 8 Participants | 11 Participants | 19.0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14.0 Participants |
| Age Continuous | 63.9 Years STANDARD_DEVIATION 9.3 | 64.9 Years STANDARD_DEVIATION 8.7 | 64.5 Years STANDARD_DEVIATION 8.8 |
| Inhaled Corticosteroid Use at Baseline No | 14 participants | 14 participants | 28.0 participants |
| Inhaled Corticosteroid Use at Baseline Yes | 1 participants | 4 participants | 5.0 participants |
| Participants Categorized by the Number of Packs Currently Smoked per Day >0 -1 pack | 5 participants | 4 participants | 9.0 participants |
| Participants Categorized by the Number of Packs Currently Smoked per Day >1 -2 packs | 3 participants | 3 participants | 6.0 participants |
| Participants Categorized by the Number of Packs Currently Smoked per Day >2 - 4 packs | 0 participants | 0 participants | 0.0 participants |
| Participants Categorized by the Number of Packs Currently Smoked per Day > 4 packs | 0 participants | 0 participants | 0.0 participants |
| Participants Categorized by the Number of Packs Currently Smoked per Day Currently does not smoke | 7 participants | 11 participants | 18.0 participants |
| Participants Categorized by the Number of Pack Years Smoked >=15 years - <25 years | 1 participants | 2 participants | 3.0 participants |
| Participants Categorized by the Number of Pack Years Smoked >=25 years - < 30 years | 0 participants | 3 participants | 3.0 participants |
| Participants Categorized by the Number of Pack Years Smoked >=30 years | 14 participants | 13 participants | 27.0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0.0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0.0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4.0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0.0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0.0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0.0 Participants |
| Race (NIH/OMB) White | 13 Participants | 16 Participants | 29.0 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13.0 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 33 | 3 / 33 |
| serious Total, serious adverse events | 0 / 33 | 0 / 33 |
Outcome results
Primary
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.
Time frame: 0-24 hours post dose
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 Mcg BID | Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 24 Hours | 0.156 liters | Standard Deviation 0.156 |
| 30 Mcg QD | Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 24 Hours | 0.173 liters | Standard Deviation 0.183 |
90% CI: [-0.015, 0.037]Mixed Models Analysis
Secondary
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.
Time frame: Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
Population: Intent to treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 4 hours post first dose (n=32,32) | 0.161 liters | Standard Deviation 0.155 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 12 hours post first dose (n=30,32) | 0.105 liters | Standard Deviation 0.167 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 30 minutes post first dose (n=32,32) | 0.168 liters | Standard Deviation 0.128 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 12.5 hours post first dose (n=30,32) | 0.193 liters | Standard Deviation 0.152 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 6 hours post first dose (n=32,30) | 0.175 liters | Standard Deviation 0.182 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 13 hours post first dose (n=30,32) | 0.223 liters | Standard Deviation 0.148 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 2 hours post first dose (n=32,32) | 0.193 liters | Standard Deviation 0.141 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 14 hours post first dose (n=30,32) | 0.232 liters | Standard Deviation 0.175 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 8 hours post first dose (n=32,30) | 0.119 liters | Standard Deviation 0.199 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 16 hours post first dose (32,32) | 0.184 liters | Standard Deviation 0.178 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 1 hour post first dose (n=32,32) | 0.179 liters | Standard Deviation 0.131 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 23 hours post first dose (n=30,31) | 0.132 liters | Standard Deviation 0.189 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 10 hours post first dose (n=30,30) | 0.145 liters | Standard Deviation 0.165 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 24 hours post first dose (n=31,31) | 0.144 liters | Standard Deviation 0.161 |
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | Immediately post first dose (n=32,32) | 0.148 liters | Standard Deviation 0.109 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 24 hours post first dose (n=31,31) | 0.120 liters | Standard Deviation 0.195 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | Immediately post first dose (n=32,32) | 0.187 liters | Standard Deviation 0.137 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 30 minutes post first dose (n=32,32) | 0.211 liters | Standard Deviation 0.157 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 1 hour post first dose (n=32,32) | 0.229 liters | Standard Deviation 0.156 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 2 hours post first dose (n=32,32) | 0.243 liters | Standard Deviation 0.16 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 4 hours post first dose (n=32,32) | 0.248 liters | Standard Deviation 0.172 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 6 hours post first dose (n=32,30) | 0.243 liters | Standard Deviation 0.181 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 8 hours post first dose (n=32,30) | 0.202 liters | Standard Deviation 0.191 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 10 hours post first dose (n=30,30) | 0.200 liters | Standard Deviation 0.203 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 12 hours post first dose (n=30,32) | 0.148 liters | Standard Deviation 0.197 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 12.5 hours post first dose (n=30,32) | 0.153 liters | Standard Deviation 0.211 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 13 hours post first dose (n=30,32) | 0.151 liters | Standard Deviation 0.198 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 14 hours post first dose (n=30,32) | 0.158 liters | Standard Deviation 0.229 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 16 hours post first dose (32,32) | 0.163 liters | Standard Deviation 0.237 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose To Each Assessed Time Point Post-Dose | 23 hours post first dose (n=30,31) | 0.088 liters | Standard Deviation 0.211 |
Secondary
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.
Time frame: pre-dose and 24 hours post-dose
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 Mcg BID | Change in Forced Expiratory Volume in One Second From Pre-dose to the 24 Hour Time Point | 0.144 liters | Standard Deviation 0.161 |
| 30 Mcg QD | Change in Forced Expiratory Volume in One Second From Pre-dose to the 24 Hour Time Point | 0.120 liters | Standard Deviation 0.195 |
90% CI: [-0.086, 0.026]Mixed Models Analysis
Secondary
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.
Time frame: immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose
Population: Intent to treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 4 hours post first dose (n=32,32) | 0.296 liters | Standard Deviation 0.308 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 12 hours post first dose (n=30,32) | 0.175 liters | Standard Deviation 0.319 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 30 minutes post first dose (n=32,32) | 0.334 liters | Standard Deviation 0.264 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 12.5 hours post first dose (n=30,32) | 0.325 liters | Standard Deviation 0.348 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 6 hours post first dose (n=32,30) | 0.304 liters | Standard Deviation 0.331 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 13 hours post first dose (n=30,32) | 0.378 liters | Standard Deviation 0.326 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 2 hours post first dose (n=32,32) | 0.355 liters | Standard Deviation 0.277 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 14 hours post first dose (n=30,32) | 0.351 liters | Standard Deviation 0.374 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 8 hours post first dose (n=32,30) | 0.231 liters | Standard Deviation 0.352 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 16 hours post first dose (n=32,32) | 0.308 liters | Standard Deviation 0.378 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 1 hour post first dose (n=32,32) | 0.352 liters | Standard Deviation 0.27 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 23 hours post first dose (n=30,31) | 0.206 liters | Standard Deviation 0.348 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 10 hours post first dose (n=30,30) | 0.246 liters | Standard Deviation 0.345 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 24 hours post first dose (n=31,31) | 0.257 liters | Standard Deviation 0.337 |
| 15 Mcg BID | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | Immediately post first dose (n=32,32) | 0.293 liters | Standard Deviation 0.24 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 24 hours post first dose (n=31,31) | 0.148 liters | Standard Deviation 0.344 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | Immediately post first dose (n=32,32) | 0.290 liters | Standard Deviation 0.274 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 30 minutes post first dose (n=32,32) | 0.340 liters | Standard Deviation 0.274 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 1 hour post first dose (n=32,32) | 0.390 liters | Standard Deviation 0.31 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 2 hours post first dose (n=32,32) | 0.411 liters | Standard Deviation 0.335 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 4 hours post first dose (n=32,32) | 0.398 liters | Standard Deviation 0.369 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 6 hours post first dose (n=32,30) | 0.384 liters | Standard Deviation 0.364 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 8 hours post first dose (n=32,30) | 0.331 liters | Standard Deviation 0.393 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 10 hours post first dose (n=30,30) | 0.297 liters | Standard Deviation 0.386 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 12 hours post first dose (n=30,32) | 0.196 liters | Standard Deviation 0.359 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 12.5 hours post first dose (n=30,32) | 0.195 liters | Standard Deviation 0.355 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 13 hours post first dose (n=30,32) | 0.214 liters | Standard Deviation 0.359 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 14 hours post first dose (n=30,32) | 0.213 liters | Standard Deviation 0.383 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 16 hours post first dose (n=32,32) | 0.183 liters | Standard Deviation 0.414 |
| 30 Mcg QD | Change in Forced Vital Capacity From Pre-dose to Each Post-Dose Assessed Time Point | 23 hours post first dose (n=30,31) | 0.088 liters | Standard Deviation 0.38 |
Secondary
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.
Time frame: Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
Population: Intent to treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 6 hours post first dose (n=32,30) | 5.576 percent of predicted FEV1 | Standard Deviation 5.237 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 12 hours post first dose (n=30,32) | 3.507 percent of predicted FEV1 | Standard Deviation 5.382 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 1 hour post first dose (n=32,32) | 5.980 percent of predicted FEV1 | Standard Deviation 4.124 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 12.5 hours post first dose (n=30,32) | 6.557 percent of predicted FEV1 | Standard Deviation 5.216 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | Immediately post first dose (n=32,32) | 4.787 percent of predicted FEV1 | Standard Deviation 3.274 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 13 hours post first dose (n=30,32) | 7.470 percent of predicted FEV1 | Standard Deviation 4.903 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 4 hours post first dose (n=32,32) | 5.399 percent of predicted FEV1 | Standard Deviation 4.82 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 14 hours post first dose (n=30,32) | 7.672 percent of predicted FEV1 | Standard Deviation 5.398 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 8 hours post first dose (n=32,30) | 3.816 percent of predicted FEV1 | Standard Deviation 6.276 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 16 hours post first dose (n=32,32) | 6.259 percent of predicted FEV1 | Standard Deviation 5.767 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 2 hours post first dose (n=32,32) | 6.570 percent of predicted FEV1 | Standard Deviation 4.607 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 23 hours post first dose (n=30,31) | 4.498 percent of predicted FEV1 | Standard Deviation 6.276 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 10 hours post first dose (n=30,30) | 4.810 percent of predicted FEV1 | Standard Deviation 5.71 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 24 hours post first dose (n=31,31) | 4.875 percent of predicted FEV1 | Standard Deviation 4.925 |
| 15 Mcg BID | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 30 minutes post first dose (n=32,32) | 5.574 percent of predicted FEV1 | Standard Deviation 3.88 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 24 hours post first dose (n=31,31) | 3.528 percent of predicted FEV1 | Standard Deviation 6.54 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 30 minutes post first dose (n=32,32) | 6.917 percent of predicted FEV1 | Standard Deviation 4.911 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 1 hour post first dose (n=32,32) | 7.437 percent of predicted FEV1 | Standard Deviation 4.578 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 2 hours post first dose (n=32,32) | 8.055 percent of predicted FEV1 | Standard Deviation 4.761 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 4 hours post first dose (n=32,32) | 8.189 percent of predicted FEV1 | Standard Deviation 5.103 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 6 hours post first dose (n=32,30) | 7.904 percent of predicted FEV1 | Standard Deviation 5.786 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | Immediately post first dose (n=32,32) | 6.028 percent of predicted FEV1 | Standard Deviation 4.296 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 8 hours post first dose (n=32,30) | 6.261 percent of predicted FEV1 | Standard Deviation 6.101 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 10 hours post first dose (n=30,30) | 6.130 percent of predicted FEV1 | Standard Deviation 6.679 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 12 hours post first dose (n=30,32) | 4.662 percent of predicted FEV1 | Standard Deviation 6.733 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 12.5 hours post first dose (n=30,32) | 4.776 percent of predicted FEV1 | Standard Deviation 7.496 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 13 hours post first dose (n=30,32) | 4.939 percent of predicted FEV1 | Standard Deviation 6.978 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 14 hours post first dose (n=30,32) | 4.927 percent of predicted FEV1 | Standard Deviation 7.734 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 16 hours post first dose (n=32,32) | 4.937 percent of predicted FEV1 | Standard Deviation 8.08 |
| 30 Mcg QD | Change in Percent of Predicted Forced Expiratory Volume at One Second (FEV1) at Each Assessed Time Point Post-Dose Compared to Pre-Dose | 23 hours post first dose (n=30,31) | 2.457 percent of predicted FEV1 | Standard Deviation 7.732 |
Secondary
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.
Time frame: 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
Population: Intent to treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 23 hours post first dose (n=30,32) | 1.297 liters | Standard Deviation 0.373 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 12.5 hours post first dose (n=30,32) | 1.359 liters | Standard Deviation 0.359 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 24 hours post first dose (n=31,32) | 1.296 liters | Standard Deviation 0.363 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 10 hours post first dose (n=31,30) | 1.308 liters | Standard Deviation 0.371 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | Pre-dose (n=32,32) | 1.184 liters | Standard Deviation 0.366 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 13 hours post first dose (n=30,32) | 1.389 liters | Standard Deviation 0.375 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | Immediately post first dose (n=32,33) | 1.332 liters | Standard Deviation 0.418 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 4 hours post first dose (n=33,33) | 1.342 liters | Standard Deviation 0.374 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 30 minutes (n=33,33) | 1.349 liters | Standard Deviation 0.392 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 14 hours post first dose (n=30,32) | 1.397 liters | Standard Deviation 0.389 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 1 hour post first dose (n=33,33) | 1.362 liters | Standard Deviation 0.387 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 12 hours post first dose (n=30,32) | 1.270 liters | Standard Deviation 0.365 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 2 hours post first dose (n=33,33) | 1.378 liters | Standard Deviation 0.375 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 16 hours post first dose (n=32,33) | 1.368 liters | Standard Deviation 0.357 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 8 hours post first dose (n=32,30) | 1.303 liters | Standard Deviation 0.402 |
| 15 Mcg BID | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 6 hours post first dose (n=32,30) | 1.359 liters | Standard Deviation 0.426 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 8 hours post first dose (n=32,30) | 1.373 liters | Standard Deviation 0.397 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 4 hours post first dose (n=33,33) | 1.429 liters | Standard Deviation 0.375 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 10 hours post first dose (n=31,30) | 1.371 liters | Standard Deviation 0.411 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 12 hours post first dose (n=30,32) | 1.327 liters | Standard Deviation 0.4 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 12.5 hours post first dose (n=30,32) | 1.332 liters | Standard Deviation 0.409 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 13 hours post first dose (n=30,32) | 1.330 liters | Standard Deviation 0.378 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 14 hours post first dose (n=30,32) | 1.337 liters | Standard Deviation 0.411 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 16 hours post first dose (n=32,33) | 1.344 liters | Standard Deviation 0.42 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 23 hours post first dose (n=30,32) | 1.252 liters | Standard Deviation 0.412 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 24 hours post first dose (n=31,32) | 1.279 liters | Standard Deviation 0.417 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | Pre-dose (n=32,32) | 1.179 liters | Standard Deviation 0.342 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | Immediately post first dose (n=32,33) | 1.358 liters | Standard Deviation 0.386 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 30 minutes (n=33,33) | 1.384 liters | Standard Deviation 0.374 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 1 hour post first dose (n=33,33) | 1.401 liters | Standard Deviation 0.394 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 6 hours post first dose (n=32,30) | 1.414 liters | Standard Deviation 0.384 |
| 30 Mcg QD | Forced Expiratory Volume in One Second Measurements Pre-dose and at Each Assessed Time Point Post-dose | 2 hours post first dose (n=33,33) | 1.419 liters | Standard Deviation 0.378 |
Secondary
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.
Time frame: 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 Mcg BID | Peak Change in Forced Expiratory Volume at One Second (FEV1) Within 12 Hours Post Dose Compared to Pre-dose | 0.269 liters | Standard Deviation 0.154 |
| 30 Mcg QD | Peak Change in Forced Expiratory Volume at One Second (FEV1) Within 12 Hours Post Dose Compared to Pre-dose | 0.324 liters | Standard Deviation 0.166 |
90% CI: [0.015, 0.09]Mixed Models Analysis
Secondary
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.
Time frame: 12 hours
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 Mcg BID | Peak Percent of Predicted Forced Expiratory Volume at One Second (FEV1) Over 12 Hours Post-Dose. | 49.399 percent of predicted FEV1 | Standard Deviation 10.738 |
| 30 Mcg QD | Peak Percent of Predicted Forced Expiratory Volume at One Second (FEV1) Over 12 Hours Post-Dose. | 51.251 percent of predicted FEV1 | Standard Deviation 10.606 |
90% CI: [0.525, 2.862]Mixed Models Analysis
Secondary
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.
Time frame: 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
Population: Intent to treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | Pre-dose (n=32,32) | 40.717 Percent of Predicted FEV1 | Standard Deviation 10.522 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | Immediately post first dose (n=32,33) | 45.504 Percent of Predicted FEV1 | Standard Deviation 10.938 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 30 min post first dose (n=33,33) | 45.990 Percent of Predicted FEV1 | Standard Deviation 10.407 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 1 hour post first dose (n=33,33) | 46.456 Percent of Predicted FEV1 | Standard Deviation 10.638 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 2 hours post first dose (n=33,33) | 47.136 Percent of Predicted FEV1 | Standard Deviation 10.393 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 4 hours post first dose (n=33,33) | 45.839 Percent of Predicted FEV1 | Standard Deviation 10.366 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 6 hours post first dose (n=32,30) | 46.294 Percent of Predicted FEV1 | Standard Deviation 10.678 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 8 hours post first dose (n=32,30) | 44.534 Percent of Predicted FEV1 | Standard Deviation 10.892 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 10 hours post first dose (n=31,30) | 44.913 Percent of Predicted FEV1 | Standard Deviation 10.947 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 12 hours post first dose (n=30,32) | 43.885 Percent of Predicted FEV1 | Standard Deviation 10.726 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 12.5 hours post dose (n=30,32) | 46.935 Percent of Predicted FEV1 | Standard Deviation 10.728 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 13 hours post first dose (n=30,32) | 47.848 Percent of Predicted FEV1 | Standard Deviation 10.703 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 14 hours post first dose (n=30,32) | 48.051 Percent of Predicted FEV1 | Standard Deviation 10.73 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 16 hours post first dose (n=32,33) | 46.977 Percent of Predicted FEV1 | Standard Deviation 10.236 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 23 hours post first dose (n=30,32) | 44.876 Percent of Predicted FEV1 | Standard Deviation 11.561 |
| 15 Mcg BID | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 24 hours post first dose (n=31,32) | 44.844 Percent of Predicted FEV1 | Standard Deviation 10.73 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 24 hours post first dose (n=31,32) | 43.729 Percent of Predicted FEV1 | Standard Deviation 11.178 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | Pre-dose (n=32,32) | 40.784 Percent of Predicted FEV1 | Standard Deviation 10.554 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 10 hours post first dose (n=31,30) | 46.360 Percent of Predicted FEV1 | Standard Deviation 10.932 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | Immediately post first dose (n=32,33) | 46.396 Percent of Predicted FEV1 | Standard Deviation 10.617 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 14 hours post first dose (n=30,32) | 45.711 Percent of Predicted FEV1 | Standard Deviation 11.116 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 30 min post first dose (n=33,33) | 47.303 Percent of Predicted FEV1 | Standard Deviation 10.25 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 12 hours post first dose (n=30,32) | 45.446 Percent of Predicted FEV1 | Standard Deviation 10.821 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 1 hour post first dose (n=33,33) | 47.816 Percent of Predicted FEV1 | Standard Deviation 10.469 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 23 hours post first dose (n=30,32) | 42.793 Percent of Predicted FEV1 | Standard Deviation 11.537 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 2 hours post first dose (n=33,33) | 48.559 Percent of Predicted FEV1 | Standard Deviation 10.352 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 12.5 hours post dose (n=30,32) | 45.560 Percent of Predicted FEV1 | Standard Deviation 11.216 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 4 hours post first dose (n=33,33) | 48.832 Percent of Predicted FEV1 | Standard Deviation 9.868 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 16 hours post first dose (n=32,33) | 45.599 Percent of Predicted FEV1 | Standard Deviation 11.074 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 6 hours post first dose (n=32,30) | 48.133 Percent of Predicted FEV1 | Standard Deviation 10.958 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 13 hours post first dose (n=30,32) | 45.723 Percent of Predicted FEV1 | Standard Deviation 11.043 |
| 30 Mcg QD | Percent of Predicted Forced Expiratory Volume at One Second at Pre-dose and Each Assessed Time Point Post-Dose | 8 hours post first dose (n=32,30) | 46.491 Percent of Predicted FEV1 | Standard Deviation 10.507 |
Secondary
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.
Time frame: 12-24 hours
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 Mcg BID | Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Between 12-24 Hours | 0.179 liters | Standard Deviation 0.154 |
| 30 Mcg QD | Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Between 12-24 Hours | 0.132 liters | Standard Deviation 0.211 |
90% CI: [-0.079, 0.008]Mixed Models Analysis
Secondary
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.
Time frame: 0-12 hours
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 Mcg BID | Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 12 Hours | 0.148 liters | Standard Deviation 0.152 |
| 30 Mcg QD | Time-Normalized Area Under the Change From Pre-Dose Curve for Forced Expiratory Volume in One Second Measured Over 12 Hours | 0.214 liters | Standard Deviation 0.163 |
90% CI: [0.035, 0.09]Mixed Models Analysis
Secondary
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.
Time frame: 12 hours post first dose
Population: Intent to treat population. Limited to those patients who had a 15% response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 15 Mcg BID | Time to Onset of 15 Percent Response Within 12 Hours of Dosing | 7.75 minutes |
| 30 Mcg QD | Time to Onset of 15 Percent Response Within 12 Hours of Dosing | 2.43 minutes |
Secondary
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.
Time frame: 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
Population: Intent to treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 Mcg BID | 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 | Pre-dose (n=32,32) | 2.545 minutes | Standard Deviation 0.718 |
| 15 Mcg BID | 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 | Immediately post first dose (n=32,33) | 2.838 minutes | Standard Deviation 0.79 |
| 15 Mcg BID | 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 | 30 minutes post first dose (n=33,33) | 2.903 minutes | Standard Deviation 0.814 |
| 15 Mcg BID | 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 | 1 hour post first dose (n=33,33) | 2.918 minutes | Standard Deviation 0.771 |
| 15 Mcg BID | 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 | 2 hours post first dose (n=33,33) | 2.931 minutes | Standard Deviation 0.804 |
| 15 Mcg BID | 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 | 4 hours post first dose (n=33,33) | 2.871 minutes | Standard Deviation 0.783 |
| 15 Mcg BID | 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 | 6 hours post first dose (n=32,30) | 2.849 minutes | Standard Deviation 0.822 |
| 15 Mcg BID | 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 | 8 hours post first dose (n=32,30) | 2.776 minutes | Standard Deviation 0.828 |
| 15 Mcg BID | 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 | 10 hours post first dose (n=31,30) | 2.796 minutes | Standard Deviation 0.852 |
| 15 Mcg BID | 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 | 12 hours post first dose (n=30,32) | 2.702 minutes | Standard Deviation 0.832 |
| 15 Mcg BID | 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 | 12.5 hours post first dose (n=30,32) | 2.852 minutes | Standard Deviation 0.832 |
| 15 Mcg BID | 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 | 13 hours post first dose (n=30,32) | 2.905 minutes | Standard Deviation 0.876 |
| 15 Mcg BID | 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 | 14 hours post first dose (n=30,32) | 2.878 minutes | Standard Deviation 0.839 |
| 15 Mcg BID | 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 | 16 hours post first dose (n=32,33) | 2.854 minutes | Standard Deviation 0.824 |
| 15 Mcg BID | 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 | 23 hours post first dose (n=30,32) | 2.733 minutes | Standard Deviation 0.834 |
| 15 Mcg BID | 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 | 24 hours post first dose (n=31,32) | 2.774 minutes | Standard Deviation 0.809 |
| 30 Mcg QD | 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 | 24 hours post first dose (n=31,32) | 2.763 minutes | Standard Deviation 0.875 |
| 30 Mcg QD | 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 | Pre-dose (n=32,32) | 2.601 minutes | Standard Deviation 0.746 |
| 30 Mcg QD | 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 | 10 hours post first dose (n=31,30) | 2.906 minutes | Standard Deviation 0.91 |
| 30 Mcg QD | 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 | Immediately post first dose (n=32,33) | 2.905 minutes | Standard Deviation 0.796 |
| 30 Mcg QD | 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 | 14 hours post first dose (n=30,32) | 2.813 minutes | Standard Deviation 0.862 |
| 30 Mcg QD | 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 | 30 minutes post first dose (n=33,33) | 2.953 minutes | Standard Deviation 0.808 |
| 30 Mcg QD | 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 | 12 hours post first dose (n=30,32) | 2.797 minutes | Standard Deviation 0.862 |
| 30 Mcg QD | 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 | 1 hour post first dose (n=33,33) | 3.003 minutes | Standard Deviation 0.846 |
| 30 Mcg QD | 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 | 23 hours post first dose (n=30,32) | 2.700 minutes | Standard Deviation 0.866 |
| 30 Mcg QD | 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 | 2 hours post first dose (n=33,33) | 3.030 minutes | Standard Deviation 0.8 |
| 30 Mcg QD | 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 | 12.5 hours post first dose (n=30,32) | 2.796 minutes | Standard Deviation 0.852 |
| 30 Mcg QD | 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 | 4 hours post first dose (n=33,33) | 3.028 minutes | Standard Deviation 0.849 |
| 30 Mcg QD | 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 | 16 hours post first dose (n=32,33) | 2.812 minutes | Standard Deviation 0.869 |
| 30 Mcg QD | 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 | 6 hours post first dose (n=32,30) | 2.993 minutes | Standard Deviation 0.844 |
| 30 Mcg QD | 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 | 13 hours post first dose (n=30,32) | 2.815 minutes | Standard Deviation 0.829 |
| 30 Mcg QD | 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 | 8 hours post first dose (n=32,30) | 2.940 minutes | Standard Deviation 0.85 |
Secondary
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
Time frame: up to 12 hours post dose
Population: Intent to treat population. Limited to patients who met both criteria: a 12 percent increase in FEV1 and a 200 milliliter increase in FEV1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 15 Mcg BID | Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase Within 12 Hours of Dosing | 12.62 minutes |
| 30 Mcg QD | Time to Onset of Response of Both a 12 Percent Increase and 200 Milliliter Increase Within 12 Hours of Dosing | 2.86 minutes |