Bronchitis, Chronic Obstructive Pulmonary Disease, Emphysema
Conditions
Keywords
COPD including chronic bronchitis and emphysema
Brief summary
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
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.
Interventions
Arformoterol tartrate inhalation solution 15 mcg twice daily and placebo inhalation powder once daily.
DRUGTiotropium
Placebo inhalation solution twice daily and tiotropium inhalation powder 18 mcg once daily.
DRUGArformoterol and Tiotropium
Arformoterol tartrate inhalation solution 15 mcg twice daily and Tiotropium inhalation powder 18 mcg once daily.
DRUGPlacebo
Placebo inhalation solution and placebo inhalation powder
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
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.
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Following 2 weeks of dosing | 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. |
| Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | 2 weeks | 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. |
| Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | 2 weeks | 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. |
| Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | 2 weeks | 12 hour peak change in FEV1 is defined as maximum of the post dose changes through the nominal 12 hour assessment. |
| Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks | 2 weeks | Analyzed from end of dosing to 12 hours. |
| Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks | 2 weeks | Analyzed from end of dosing to 12 hours. |
| Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B) | 0-12 hours following two weeks of dosing | — |
| 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 | 2 weeks | 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. |
| Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | 2 weeks | 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. |
| Transition Dyspnea Index (TDI) Focal Score | 2 weeks | 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. |
| Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score | 2 weeks | A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. |
| Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score | 2 weeks | A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. |
| Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing | 2 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Multicenter (34 sites) study.
Pre-assignment details
Started: consists of all subjects who were randomized to treatment and received at least one dose of randomized study drug (Intent to treat population). One patient was randomized to the arformoterol/tiotropium group but discontinued before receiving any study medication and is therefore not included.
Participants by arm
| Arm | Count |
|---|---|
| Arformoterol 15 Mcg Twice Daily Arformoterol 15 mcg twice daily/Placebo Inhalation Powder | 76 |
| Tiotropium 18 Mcg Once Daily Tiotropium 18 mcg once daily/Placebo Inhalation Solution | 80 |
| Arformoterol /Tiotropium Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily | 78 |
| Total | 234 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | noncompliance with study requirements | 2 | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Arformoterol 15 Mcg Twice Daily | Tiotropium 18 Mcg Once Daily | Arformoterol /Tiotropium | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 30 Participants | 26 Participants | 85 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 50 Participants | 52 Participants | 149 Participants |
| Age Continuous | 61.6 years STANDARD_DEVIATION 8.4 | 61.2 years STANDARD_DEVIATION 9.5 | 62.2 years STANDARD_DEVIATION 7.6 | 61.7 years STANDARD_DEVIATION 8.5 |
| Baseline Dyspnea Index (BDI) Focal Score | 5.8 units on a scale STANDARD_DEVIATION 2 | 5.8 units on a scale STANDARD_DEVIATION 1.9 | 5.5 units on a scale STANDARD_DEVIATION 2.1 | 5.7 units on a scale STANDARD_DEVIATION 2 |
| Best Forced Expiratory Volume in one second (FEV1)/Best Forced Vital Capacity (FVC) ratio | 0.510 Liters STANDARD_DEVIATION 0.098 | 0.514 Liters STANDARD_DEVIATION 0.107 | 0.525 Liters STANDARD_DEVIATION 0.108 | 0.516 Liters STANDARD_DEVIATION 0.104 |
| FEV1 | 1.366 Liters STANDARD_DEVIATION 0.457 | 1.377 Liters STANDARD_DEVIATION 0.46 | 1.350 Liters STANDARD_DEVIATION 0.408 | 1.365 Liters STANDARD_DEVIATION 0.44 |
| FEV1 Percent Predicted | 45.4 percent predicted of FEV1 STANDARD_DEVIATION 11.9 | 45.7 percent predicted of FEV1 STANDARD_DEVIATION 11.5 | 44.9 percent predicted of FEV1 STANDARD_DEVIATION 12 | 45.4 percent predicted of FEV1 STANDARD_DEVIATION 11.8 |
| Inspiratory Capacity | 2.005 Liters STANDARD_DEVIATION 0.615 | 1.979 Liters STANDARD_DEVIATION 0.555 | 1.924 Liters STANDARD_DEVIATION 0.516 | 1.969 Liters STANDARD_DEVIATION 0.562 |
| Modified Medical Research Council Dyspnea Questionnaire | 2.7 units on a scale STANDARD_DEVIATION 0.6 | 2.9 units on a scale STANDARD_DEVIATION 0.7 | 2.9 units on a scale STANDARD_DEVIATION 0.6 | 2.8 units on a scale STANDARD_DEVIATION 0.6 |
| Number of Pack Years Smoked >=15 years to <25 years | 0 Participants | 1 Participants | 6 Participants | 7 Participants |
| Number of Pack Years Smoked >=25 years to <=30 years | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Number of Pack Years Smoked >=30 years | 72 Participants | 75 Participants | 68 Participants | 215 Participants |
| Packs per day currently smoked >0 to 1 pack | 24 Participants | 30 Participants | 22 Participants | 76 Participants |
| Packs per day currently smoked >1 to 2 packs | 22 Participants | 24 Participants | 16 Participants | 62 Participants |
| Packs per day currently smoked >2 to 4 packs | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Packs per day currently smoked >4 packs | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Packs per day currently smoked Currently does not smoke | 27 Participants | 26 Participants | 39 Participants | 92 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 6 Participants | 7 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 71 Participants | 74 Participants | 70 Participants | 215 Participants |
| Region of Enrollment United States | 76 participants | 80 participants | 78 participants | 234 participants |
| Sex: Female, Male Female | 37 Participants | 37 Participants | 36 Participants | 110 Participants |
| Sex: Female, Male Male | 39 Participants | 43 Participants | 42 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / — | 12 / — | 16 / — |
| serious Total, serious adverse events | 1 / — | 0 / — | 0 / — |
Outcome results
Primary
Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)
Time frame: 24 hours following two weeks of dosing.
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B) | 0.104 Liters |
| Tiotropium 18 Mcg Once Daily | Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B) | 0.080 Liters |
| Arformoterol /Tiotropium | Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B) | 0.221 Liters |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
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.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 30 minutes post first dose; N=70, 74, 74 | 0.188 Liters | Standard Deviation 0.222 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 14 hours post first dose; N=65, 71, 72 | 0.182 Liters | Standard Deviation 0.248 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 30 minutes post first dose; N=75, 78, 76 | 0.163 Liters | Standard Deviation 0.137 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 0.143 Liters | Standard Deviation 0.235 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 2 hours post first dose; N=76, 78, 77 | 0.193 Liters | Standard Deviation 0.156 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 6 hours post first dose; N=72, 74, 77 | 0.128 Liters | Standard Deviation 0.156 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 1 hour post first dose; N=75, 78, 77 | 0.182 Liters | Standard Deviation 0.15 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 16 hours post first dose; N=63, 70, 71 | 0.114 Liters | Standard Deviation 0.233 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: immediately post second dose; N=65, 67, 72 | 0.115 Liters | Standard Deviation 0.223 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 8 hours post first dose; N=70, 73, 77 | 0.102 Liters | Standard Deviation 0.183 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: immediately post first dose; N=71, 75, 74 | 0.154 Liters | Standard Deviation 0.207 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 8 hours post first dose; N=69, 70, 74 | 0.067 Liters | Standard Deviation 0.221 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 4 hours post first dose; N=75, 77, 77 | 0.155 Liters | Standard Deviation 0.169 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 1 hour post first dose; N=71, 75, 73 | 0.185 Liters | Standard Deviation 0.222 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 23 hours post first dose; N=70, 74, 74 | 0.040 Liters | Standard Deviation 0.236 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 10 hours post first dose; N=69, 71, 76 | 0.101 Liters | Standard Deviation 0.15 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 2 hours post first dose; N=71, 73, 74 | 0.213 Liters | Standard Deviation 0.226 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 6 hours post first dose; N=69, 72, 73 | 0.123 Liters | Standard Deviation 0.211 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 13 hours post first dose; N=63, 68, 72 | 0.159 Liters | Standard Deviation 0.234 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 4 hours post first dose; N=69, 72, 74 | 0.154 Liters | Standard Deviation 0.227 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 24 hours post first dose; N=69, 73, 74 | 0.086 Liters | Standard Deviation 0.229 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12 hours post first dose; N=63, 67, 71 | 0.035 Liters | Standard Deviation 0.211 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 12 hours post first dose; N=69, 71, 75 | 0.044 Liters | Standard Deviation 0.181 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 10 hours post first dose; N=69, 71, 71 | 0.054 Liters | Standard Deviation 0.224 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: immediately post first dose; N=76, 78, 78 | 0.132 Liters | Standard Deviation 0.155 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 10 hours post first dose; N=69, 71, 71 | 0.109 Liters | Standard Deviation 0.179 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12 hours post first dose; N=63, 67, 71 | 0.101 Liters | Standard Deviation 0.204 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 1 hour post first dose; N=75, 78, 77 | 0.106 Liters | Standard Deviation 0.141 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: immediately post second dose; N=65, 67, 72 | 0.040 Liters | Standard Deviation 0.215 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 0.063 Liters | Standard Deviation 0.213 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 13 hours post first dose; N=63, 68, 72 | 0.061 Liters | Standard Deviation 0.196 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 6 hours post first dose; N=69, 72, 73 | 0.143 Liters | Standard Deviation 0.226 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 14 hours post first dose; N=65, 71, 72 | 0.068 Liters | Standard Deviation 0.221 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 16 hours post first dose; N=63, 70, 71 | 0.048 Liters | Standard Deviation 0.239 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 23 hours post first dose; N=70, 74, 74 | -0.006 Liters | Standard Deviation 0.212 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 8 hours post first dose; N=69, 70, 74 | 0.138 Liters | Standard Deviation 0.233 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 24 hours post first dose; N=69, 73, 74 | 0.080 Liters | Standard Deviation 0.207 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: immediately post first dose; N=76, 78, 78 | -0.20 Liters | Standard Deviation 0.084 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 6 hours post first dose; N=72, 74, 77 | 0.125 Liters | Standard Deviation 0.188 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 30 minutes post first dose; N=75, 78, 76 | 0.056 Liters | Standard Deviation 0.093 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 2 hours post first dose; N=76, 78, 77 | 0.140 Liters | Standard Deviation 0.148 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 8 hours post first dose; N=70, 73, 77 | 0.109 Liters | Standard Deviation 0.208 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 12 hours post first dose; N=69, 71, 75 | 0.094 Liters | Standard Deviation 0.196 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 30 minutes post first dose; N=70, 74, 74 | 0.126 Liters | Standard Deviation 0.2 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 1 hour post first dose; N=71, 75, 73 | 0.163 Liters | Standard Deviation 0.251 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 2 hours post first dose; N=71, 73, 74 | 0.195 Liters | Standard Deviation 0.248 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 10 hours post first dose; N=69, 71, 76 | 0.111 Liters | Standard Deviation 0.184 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 4 hours post first dose; N=69, 72, 74 | 0.164 Liters | Standard Deviation 0.25 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 4 hours post first dose; N=75, 77, 77 | 0.120 Liters | Standard Deviation 0.169 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: immediately post first dose; N=71, 75, 74 | 0.066 Liters | Standard Deviation 0.184 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 24 hours post first dose; N=69, 73, 74 | 0.154 Liters | Standard Deviation 0.223 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 30 minutes post first dose; N=75, 78, 76 | 0.183 Liters | Standard Deviation 0.152 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 1 hour post first dose; N=75, 78, 77 | 0.189 Liters | Standard Deviation 0.161 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 4 hours post first dose; N=75, 77, 77 | 0.223 Liters | Standard Deviation 0.189 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 6 hours post first dose; N=72, 74, 77 | 0.214 Liters | Standard Deviation 0.184 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 8 hours post first dose; N=70, 73, 77 | 0.194 Liters | Standard Deviation 0.18 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 10 hours post first dose; N=69, 71, 76 | 0.190 Liters | Standard Deviation 0.176 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: immediately post first dose; N=71, 75, 74 | 0.240 Liters | Standard Deviation 0.206 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 6 hours post first dose; N=69, 72, 73 | 0.266 Liters | Standard Deviation 0.208 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: immediately post first dose; N=76, 78, 78 | 0.139 Liters | Standard Deviation 0.151 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 2 hours post first dose; N=76, 78, 77 | 0.239 Liters | Standard Deviation 0.17 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 12 hours post first dose; N=69, 71, 75 | 0.199 Liters | Standard Deviation 0.202 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 30 minutes post first dose; N=70, 74, 74 | 0.280 Liters | Standard Deviation 0.216 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 1 hour post first dose; N=71, 75, 73 | 0.308 Liters | Standard Deviation 0.232 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 2 hours post first dose; N=71, 73, 74 | 0.330 Liters | Standard Deviation 0.228 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 4 hours post first dose; N=69, 72, 74 | 0.279 Liters | Standard Deviation 0.239 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 8 hours post first dose; N=69, 70, 74 | 0.220 Liters | Standard Deviation 0.215 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 10 hours post first dose; N=69, 71, 71 | 0.205 Liters | Standard Deviation 0.211 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12 hours post first dose; N=63, 67, 71 | 0.189 Liters | Standard Deviation 0.21 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: immediately post second dose; N=65, 67, 72 | 0.235 Liters | Standard Deviation 0.202 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 0.270 Liters | Standard Deviation 0.214 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 13 hours post first dose; N=63, 68, 72 | 0.272 Liters | Standard Deviation 0.22 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 14 hours post first dose; N=65, 71, 72 | 0.292 Liters | Standard Deviation 0.234 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 16 hours post first dose; N=63, 70, 71 | 0.240 Liters | Standard Deviation 0.216 |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 23 hours post first dose; N=70, 74, 74 | 0.145 Liters | Standard Deviation 0.208 |
Secondary
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.
Time frame: Following 2 weeks of dosing
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough) | 0.086 Liters |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough) | 0.080 Liters |
| Arformoterol /Tiotropium | Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough) | 0.154 Liters |
p-value: 0.073ANCOVA
p-value: 0.05ANCOVA
Secondary
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.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 12 hours post first dose; N=69, 71, 75 | 1.6 Percent of predicted FEV1 | Standard Deviation 6 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 24 hours post first dose; N=69, 73, 74 | 2.8 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 10 hours post first dose; N=69, 71, 71 | 1.8 Percent of predicted FEV1 | Standard Deviation 7.2 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: Immediately post first dose; N=71, 75, 74 | 5.1 Percent of predicted FEV1 | Standard Deviation 6.4 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: Immediately post first dose; N=76, 78, 78 | 4.3 Percent of predicted FEV1 | Standard Deviation 4.6 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 8 hours post first dose; N=69, 70, 74 | 2.0 Percent of predicted FEV1 | Standard Deviation 7 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 30 minutes post first dose; N=70, 74, 74 | 6.2 Percent of predicted FEV1 | Standard Deviation 7 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 23 hours post first dose; N=70, 74, 74 | 1.3 Percent of predicted FEV1 | Standard Deviation 7 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 6 hours post first dose; N=69, 72, 73 | 4.0 Percent of predicted FEV1 | Standard Deviation 6.3 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 1 hour post first dose; N=71, 75, 73 | 6.2 Percent of predicted FEV1 | Standard Deviation 7.1 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 14 hours post first dose; N=65, 71, 72 | 6.0 Percent of predicted FEV1 | Standard Deviation 7.6 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 4 hours post first dose; N=69, 72, 74 | 5.1 Percent of predicted FEV1 | Standard Deviation 7.4 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 2 hours post first dose; N=71, 73, 74 | 7.1 Percent of predicted FEV1 | Standard Deviation 7.1 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 30 minutes post first dose; N=75, 78, 76 | 5.5 Percent of predicted FEV1 | Standard Deviation 4.4 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 1 hour post first dose; N-75, 78, 77 | 6.1 Percent of predicted FEV1 | Standard Deviation 4.8 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 6 hours post first dose; N=72, 74, 77 | 4.4 Percent of predicted FEV1 | Standard Deviation 5 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 13 hours post first dose; N=63, 68, 72 | 5.4 Percent of predicted FEV1 | Standard Deviation 7.3 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 2 hours post first dose; N=76, 78, 77 | 6.6 Percent of predicted FEV1 | Standard Deviation 5 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 10 hours post first dose; N=69, 71, 76 | 3.3 Percent of predicted FEV1 | Standard Deviation 4.6 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 4.9 Percent of predicted FEV1 | Standard Deviation 7.2 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 4 hours post first dose; N=75, 77, 77 | 5.3 Percent of predicted FEV1 | Standard Deviation 5.5 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: Immediately post second dose; N=65, 67, 72 | 3.8 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 8 hours post first dose; N=70, 73, 77 | 3.5 Percent of predicted FEV1 | Standard Deviation 5.5 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 16 hours post first dose; N=63, 70, 71 | 3.9 Percent of predicted FEV1 | Standard Deviation 7.1 |
| Arformoterol 15 Mcg Twice Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12 hours post first dose; N=63, 67, 71 | 1.3 Percent of predicted FEV1 | Standard Deviation 6.7 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 2 hours post first dose; N=76, 78, 77 | 4.7 Percent of predicted FEV1 | Standard Deviation 5.1 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 4 hours post first dose; N=75, 77, 77 | 4.0 Percent of predicted FEV1 | Standard Deviation 5.3 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 10 hours post first dose; N=69, 71, 76 | 3.7 Percent of predicted FEV1 | Standard Deviation 5.6 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 14 hours post first dose; N=65, 71, 72 | 2.0 Percent of predicted FEV1 | Standard Deviation 6.7 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: Immediately post first dose; N=76, 78, 78 | -0.6 Percent of predicted FEV1 | Standard Deviation 2.5 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 1 hour post first dose; N-75, 78, 77 | 3.5 Percent of predicted FEV1 | Standard Deviation 4.6 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 30 minutes post first dose; N=75, 78, 76 | 2.0 Percent of predicted FEV1 | Standard Deviation 3.2 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 6 hours post first dose; N=72, 74, 77 | 4.1 Percent of predicted FEV1 | Standard Deviation 5.9 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 8 hours post first dose; N=70, 73, 77 | 3.5 Percent of predicted FEV1 | Standard Deviation 6.5 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 12 hours post first dose; N=69, 71, 75 | 2.9 Percent of predicted FEV1 | Standard Deviation 6.1 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: Immediately post first dose; N=71, 75, 74 | 1.9 Percent of predicted FEV1 | Standard Deviation 5.9 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 30 minutes post first dose; N=70, 74, 74 | 4.0 Percent of predicted FEV1 | Standard Deviation 6.3 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 1 hour post first dose; N=71, 75, 73 | 5.2 Percent of predicted FEV1 | Standard Deviation 7.6 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 2 hours post first dose; N=71, 73, 74 | 6.3 Percent of predicted FEV1 | Standard Deviation 7.3 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 4 hours post first dose; N=69, 72, 74 | 5.1 Percent of predicted FEV1 | Standard Deviation 7.5 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 6 hours post first dose; N=69, 72, 73 | 4.7 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 8 hours post first dose; N=69, 70, 74 | 4.4 Percent of predicted FEV1 | Standard Deviation 7.1 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 10 hours post first dose; N=69, 71, 71 | 3.5 Percent of predicted FEV1 | Standard Deviation 5.7 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12 hours post first dose; N=63, 67, 71 | 3.4 Percent of predicted FEV1 | Standard Deviation 6.3 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: Immediately post second dose; N=65, 67, 72 | 1.1 Percent of predicted FEV1 | Standard Deviation 6.8 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 2.0 Percent of predicted FEV1 | Standard Deviation 6.5 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 13 hours post first dose; N=63, 68, 72 | 1.8 Percent of predicted FEV1 | Standard Deviation 6 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 16 hours post first dose; N=63, 70, 71 | 1.4 Percent of predicted FEV1 | Standard Deviation 7.3 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 23 hours post first dose; N=70, 74, 74 | -0.2 Percent of predicted FEV1 | Standard Deviation 6.5 |
| Tiotropium 18 Mcg Once Daily | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 24 hours post first dose; N=69, 73, 74 | 2.6 Percent of predicted FEV1 | Standard Deviation 6.6 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 30 minutes post first dose; N=75, 78, 76 | 6.1 Percent of predicted FEV1 | Standard Deviation 5.2 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 10 hours post first dose; N=69, 71, 71 | 6.8 Percent of predicted FEV1 | Standard Deviation 6.8 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 8 hours post first dose; N=70, 73, 77 | 6.6 Percent of predicted FEV1 | Standard Deviation 6.2 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 16 hours post first dose; N=63, 70, 71 | 8.0 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12 hours post first dose; N=63, 67, 71 | 6.3 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 6 hours post first dose; N=72, 74, 77 | 7.3 Percent of predicted FEV1 | Standard Deviation 6.3 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 4 hours post first dose; N=75, 77, 77 | 7.5 Percent of predicted FEV1 | Standard Deviation 6.3 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: Immediately post second dose; N=65, 67, 72 | 7.8 Percent of predicted FEV1 | Standard Deviation 6.6 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 2 hours post first dose; N=76, 78, 77 | 8.1 Percent of predicted FEV1 | Standard Deviation 5.7 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 24 hours post first dose; N=69, 73, 74 | 5.2 Percent of predicted FEV1 | Standard Deviation 7.2 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 9.0 Percent of predicted FEV1 | Standard Deviation 7 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 1 hour post first dose; N-75, 78, 77 | 6.3 Percent of predicted FEV1 | Standard Deviation 5.4 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 23 hours post first dose; N=70, 74, 74 | 4.8 Percent of predicted FEV1 | Standard Deviation 6.7 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 13 hours post first dose; N=63, 68, 72 | 9.1 Percent of predicted FEV1 | Standard Deviation 7.1 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 2 hours post first dose; N=71, 73, 74 | 11.0 Percent of predicted FEV1 | Standard Deviation 7.4 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 1 hour post first dose; N=71, 75, 73 | 10.2 Percent of predicted FEV1 | Standard Deviation 7.3 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: Immediately post first dose; N=76, 78, 78 | 4.7 Percent of predicted FEV1 | Standard Deviation 4.9 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 4 hours post first dose; N=69, 72, 74 | 9.2 Percent of predicted FEV1 | Standard Deviation 7.6 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 30 minutes post first dose; N=70, 74, 74 | 9.3 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 14 hours post first dose; N=65, 71, 72 | 9.8 Percent of predicted FEV1 | Standard Deviation 7.7 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 6 hours post first dose; N=69, 72, 73 | 8.8 Percent of predicted FEV1 | Standard Deviation 6.6 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: Immediately post first dose; N=71, 75, 74 | 8.0 Percent of predicted FEV1 | Standard Deviation 6.7 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 10 hours post first dose; N=69, 71, 76 | 6.5 Percent of predicted FEV1 | Standard Deviation 5.9 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 2: 8 hours post first dose; N=69, 70, 74 | 7.4 Percent of predicted FEV1 | Standard Deviation 6.9 |
| Arformoterol /Tiotropium | Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication | Week 0: 12 hours post first dose; N=69, 71, 75 | 6.7 Percent of predicted FEV1 | Standard Deviation 6.6 |
Secondary
Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint
Time frame: 2 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 6 hours post first dose; N=72, 74, 77 | 0.242 Liters | Standard Deviation 0.303 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 24 hours post first dose; N=69, 73, 74 | 0.138 Liters | Standard Deviation 0.365 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 6 hours post first dose; N=69, 72, 73 | 0.202 Liters | Standard Deviation 0.322 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 8 hours post first dose; N=70, 73, 77 | 0.207 Liters | Standard Deviation 0.334 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 14 hours post first dose; N=65, 71, 72 | 0.343 Liters | Standard Deviation 0.386 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 4 hours post first dose; N=69, 72, 74 | 0.265 Liters | Standard Deviation 0.342 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 10 hours post first dose; N=69, 71, 76 | 0.209 Liters | Standard Deviation 0.267 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 1 hour post first dose; N=71, 75, 73 | 0.350 Liters | Standard Deviation 0.397 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 2 hours post first dose; N=71, 73, 74 | 0.380 Liters | Standard Deviation 0.389 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 12 hours post first dose; N=69, 71, 75 | 0.131 Liters | Standard Deviation 0.299 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 13 hours post first dose; N=63, 68, 72 | 0.307 Liters | Standard Deviation 0.376 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 30 minutes post first dose; N=70, 74, 74 | 0.343 Liters | Standard Deviation 0.381 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: Immediately post first dose; N=71, 75, 74 | 0.293 Liters | Standard Deviation 0.368 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 30 minutes post first dose; N=75, 78, 76 | 0.312 Liters | Standard Deviation 0.267 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: Immediately post first dose; N=76, 78, 78 | 0.276 Liters | Standard Deviation 0.27 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 0.262 Liters | Standard Deviation 0.416 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 1 hour post first dose; N=75, 78, 77 | 0.344 Liters | Standard Deviation 0.275 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 23 hours post first dose; N=70, 74, 74 | 0.082 Liters | Standard Deviation 0.363 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: Immediately post second dose; N=65, 67, 72 | 0.210 Liters | Standard Deviation 0.397 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 2 hours post first dose; N=76, 78, 77 | 0.376 Liters | Standard Deviation 0.319 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 16 hours post first dose; N=63, 70, 71 | 0.215 Liters | Standard Deviation 0.374 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 12 hours post first dose; N=63, 67, 71 | 0.087 Liters | Standard Deviation 0.34 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 4 hours post first dose; N=75, 77, 77 | 0.291 Liters | Standard Deviation 0.341 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 10 hours post first dose; N=69, 71, 71 | 0.098 Liters | Standard Deviation 0.364 |
| Arformoterol 15 Mcg Twice Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 8 hours post first dose; N=69, 70, 74 | 0.136 Liters | Standard Deviation 0.347 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: Immediately post second dose; N=65, 67, 72 | 0.034 Liters | Standard Deviation 0.356 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 30 minutes post first dose; N=70, 74, 74 | 0.203 Liters | Standard Deviation 0.35 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 1 hour post first dose; N=71, 75, 73 | 0.224 Liters | Standard Deviation 0.408 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 10 hours post first dose; N=69, 71, 71 | 0.158 Liters | Standard Deviation 0.278 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: Immediately post first dose; N=76, 78, 78 | -0.031 Liters | Standard Deviation 0.165 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 30 minutes post first dose; N=75, 78, 76 | 0.122 Liters | Standard Deviation 0.21 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 1 hour post first dose; N=75, 78, 77 | 0.197 Liters | Standard Deviation 0.283 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 2 hours post first dose; N=76, 78, 77 | 0.248 Liters | Standard Deviation 0.279 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 4 hours post first dose; N=75, 77, 77 | 0.206 Liters | Standard Deviation 0.293 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 6 hours post first dose; N=72, 74, 77 | 0.195 Liters | Standard Deviation 0.327 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 8 hours post first dose; N=70, 73, 77 | 0.159 Liters | Standard Deviation 0.36 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 10 hours post first dose; N=69, 71, 76 | 0.175 Liters | Standard Deviation 0.311 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 12 hours post first dose; N=69, 71, 75 | 0.146 Liters | Standard Deviation 0.325 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: Immediately post first dose; N=71, 75, 74 | 0.055 Liters | Standard Deviation 0.301 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 2 hours post first dose; N=71, 73, 74 | 0.290 Liters | Standard Deviation 0.387 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 4 hours post first dose; N=69, 72, 74 | 0.221 Liters | Standard Deviation 0.372 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 6 hours post first dose; N=69, 72, 73 | 0.209 Liters | Standard Deviation 0.356 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 8 hours post first dose; N=69, 70, 74 | 0.214 Liters | Standard Deviation 0.319 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 12 hours post first dose; N=63, 67, 71 | 0.124 Liters | Standard Deviation 0.365 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 0.087 Liters | Standard Deviation 0.359 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 13 hours post first dose; N=63, 68, 72 | 0.082 Liters | Standard Deviation 0.329 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 14 hours post first dose; N=65, 71, 72 | 0.110 Liters | Standard Deviation 0.342 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 16 hours post first dose; N=63, 70, 71 | 0.098 Liters | Standard Deviation 0.361 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 23 hours post first dose; N=70, 74, 74 | -0.011 Liters | Standard Deviation 0.34 |
| Tiotropium 18 Mcg Once Daily | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 24 hours post first dose; N=69, 73, 74 | 0.115 Liters | Standard Deviation 0.335 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 4 hours post first dose; N=75, 77, 77 | 0.392 Liters | Standard Deviation 0.375 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 8 hours post first dose; N=69, 70, 74 | 0.349 Liters | Standard Deviation 0.387 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 2 hours post first dose; N=76, 78, 77 | 0.429 Liters | Standard Deviation 0.366 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 30 minutes post first dose; N=70, 74, 74 | 0.461 Liters | Standard Deviation 0.425 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 12 hours post first dose; N=63, 67, 71 | 0.301 Liters | Standard Deviation 0.398 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 1 hour post first dose; N=75, 78, 77 | 0.351 Liters | Standard Deviation 0.348 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 10 hours post first dose; N=69, 71, 71 | 0.323 Liters | Standard Deviation 0.379 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: Immediately post second dose; N=65, 67, 72 | 0.360 Liters | Standard Deviation 0.385 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 30 minutes post first dose; N=75, 78, 76 | 0.323 Liters | Standard Deviation 0.347 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 1 hour post first dose; N=71, 75, 73 | 0.487 Liters | Standard Deviation 0.426 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 12.5 hours post first dose; N=65, 66, 72 | 0.399 Liters | Standard Deviation 0.407 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: Immediately post first dose; N=76, 78, 78 | 0.259 Liters | Standard Deviation 0.305 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 24 hours post first dose; N=69, 73, 74 | 0.250 Liters | Standard Deviation 0.408 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 13 hours post first dose; N=63, 68, 72 | 0.424 Liters | Standard Deviation 0.432 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: Immediately post first dose; N=71, 75, 74 | 0.389 Liters | Standard Deviation 0.392 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 12 hours post first dose; N=69, 71, 75 | 0.344 Liters | Standard Deviation 0.352 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 10 hours post first dose; N=69, 71, 76 | 0.346 Liters | Standard Deviation 0.357 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 16 hours post first dose; N=63, 70, 71 | 0.374 Liters | Standard Deviation 0.422 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 2 hours post first dose; N=71, 73, 74 | 0.526 Liters | Standard Deviation 0.426 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 8 hours post first dose; N=70, 73, 77 | 0.338 Liters | Standard Deviation 0.325 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 23 hours post first dose; N=70, 74, 74 | 0.226 Liters | Standard Deviation 0.345 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 4 hours post first dose; N=69, 72, 74 | 0.461 Liters | Standard Deviation 0.441 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 0: 6 hours post first dose; N=72, 74, 77 | 0.371 Liters | Standard Deviation 0.352 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 14 hours post first dose; N=65, 71, 72 | 0.459 Liters | Standard Deviation 0.445 |
| Arformoterol /Tiotropium | Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint | Week 2: 6 hours post first dose; N=69, 72, 73 | 0.413 Liters | Standard Deviation 0.383 |
Secondary
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.
Time frame: 2 weeks
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing | 0.074 Liters |
| Tiotropium 18 Mcg Once Daily | Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing | 0.023 Liters |
| Arformoterol /Tiotropium | Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing | 0.150 Liters |
p-value: 0.206ANCOVA
p-value: 0.025ANCOVA
Secondary
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.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Baseline: Number of actuations per day | 3.24 Actuations per day |
| Arformoterol 15 Mcg Twice Daily | Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Overall: Number of actuations per day | 1.18 Actuations per day |
| Tiotropium 18 Mcg Once Daily | Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Baseline: Number of actuations per day | 2.77 Actuations per day |
| Tiotropium 18 Mcg Once Daily | Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Overall: Number of actuations per day | 1.00 Actuations per day |
| Arformoterol /Tiotropium | Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Baseline: Number of actuations per day | 3.08 Actuations per day |
| Arformoterol /Tiotropium | Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day | Overall: Number of actuations per day | 0.68 Actuations per day |
Secondary
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.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Baseline: Number of days used per week | 4.44 Days per week |
| Arformoterol 15 Mcg Twice Daily | Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Overall: Number of days used per week | 2.16 Days per week |
| Tiotropium 18 Mcg Once Daily | Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Baseline: Number of days used per week | 4.27 Days per week |
| Tiotropium 18 Mcg Once Daily | Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Overall: Number of days used per week | 1.94 Days per week |
| Arformoterol /Tiotropium | Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Baseline: Number of days used per week | 4.57 Days per week |
| Arformoterol /Tiotropium | Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week | Overall: Number of days used per week | 1.38 Days per week |
Secondary
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.
Time frame: 2 weeks
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score | 50 Participants |
| Tiotropium 18 Mcg Once Daily | Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score | 44 Participants |
| Arformoterol /Tiotropium | Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score | 60 Participants |
Secondary
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.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | Week 2; N=71, 75, 74 | 0.273 Liters |
| Arformoterol 15 Mcg Twice Daily | Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | Week 0; N=76, 79, 78 | 0.264 Liters |
| Tiotropium 18 Mcg Once Daily | Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | Week 2; N=71, 75, 74 | 0.265 Liters |
| Tiotropium 18 Mcg Once Daily | Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | Week 0; N=76, 79, 78 | 0.218 Liters |
| Arformoterol /Tiotropium | Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | Week 2; N=71, 75, 74 | 0.379 Liters |
| Arformoterol /Tiotropium | Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline | Week 0; N=76, 79, 78 | 0.311 Liters |
Comparison: Week 0 comparisonsp-value: 0.06ANCOVA
Comparison: Week 0p-value: <0.001ANCOVA
Comparison: Week 2 comparisonsp-value: 0.004ANCOVA
Comparison: Week 2 comparisonsp-value: 0.002ANCOVA
Secondary
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.
Time frame: 2 weeks
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score | 66.67 Percentage of participants |
| Tiotropium 18 Mcg Once Daily | Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score | 57.14 Percentage of participants |
| Arformoterol /Tiotropium | Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score | 77.92 Percentage of participants |
Secondary
Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)
Time frame: 0-12 hours following two weeks of dosing
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B) | 0.118 Liters |
| Tiotropium 18 Mcg Once Daily | Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B) | 0.130 Liters |
| Arformoterol /Tiotropium | Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B) | 0.242 Liters |
p-value: <0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)
Time frame: Following 2 weeks of dosing
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B) | 0.094 Liters |
| Tiotropium 18 Mcg Once Daily | Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B) | 0.054 Liters |
| Arformoterol /Tiotropium | Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B) | 0.217 Liters |
p-value: 0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
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.
Time frame: 2 weeks
Population: Total number of subjects in each arm: 76, 80, 78.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks | 0.39 Hours |
| Tiotropium 18 Mcg Once Daily | Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks | 0.72 Hours |
| Arformoterol /Tiotropium | Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks | 0.17 Hours |
Secondary
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.
Time frame: 2 weeks
Population: Total number of subjects in each arm: 76, 80, 78.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks | 0.76 Hours |
| Tiotropium 18 Mcg Once Daily | Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks | 1.29 Hours |
| Arformoterol /Tiotropium | Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks | 0.39 Hours |
Secondary
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.
Time frame: 2 weeks
Population: Total number of subjects in each arm: 76, 80, 78
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arformoterol 15 Mcg Twice Daily | Transition Dyspnea Index (TDI) Focal Score | 2.28 Units on a scale | Standard Deviation 2.39 |
| Tiotropium 18 Mcg Once Daily | Transition Dyspnea Index (TDI) Focal Score | 1.79 Units on a scale | Standard Deviation 2.83 |
| Arformoterol /Tiotropium | Transition Dyspnea Index (TDI) Focal Score | 3.13 Units on a scale | Standard Deviation 2.44 |