Trial Outcomes & Findings for Safety and Efficacy of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease (NCT NCT00250679)

NCT ID: NCT00250679

Last Updated: 2012-06-04

Results Overview

Percent of participants with the adverse event specified. SOC = system organ class.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 443 participants
• Primary outcome timeframe: Six months
• Results posted on: 2012-06-04

Participant Flow

Two patients were each issued two randomization numbers; both subjects are included only once in the intent-to-treat (ITT) population. One additional subject was randomized in error and did not receive study drug. This subject is excluded from the ITT population.

Participant milestones

Measure	Formoterol 12 Mcg 2x/Day	Arformoterol 15 Mcg 2x/Day	Arformoterol 25 Mcg 2x/Day
Overall Study STARTED	147	149	147
Overall Study COMPLETED	108	100	103
Overall Study NOT COMPLETED	39	49	44

Reasons for withdrawal

Measure	Formoterol 12 Mcg 2x/Day	Arformoterol 15 Mcg 2x/Day	Arformoterol 25 Mcg 2x/Day
Overall Study Adverse Event	12	15	16
Overall Study Protocol Violation	2	4	3
Overall Study Withdrawal by Subject	15	18	15
Overall Study Lost to Follow-up	3	4	2
Overall Study Does Not Meet Entry Criteria	1	4	2
Overall Study Lack of Efficacy	0	1	3
Overall Study Technical Holter issues	1	0	2
Overall Study Moved	1	1	0
Overall Study Non-compliance	1	1	0
Overall Study various single events: hip surgery,diary	3	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants	Total n=443 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	77 Participants n=93 Participants	71 Participants n=4 Participants	77 Participants n=27 Participants	225 Participants n=483 Participants
Age, Categorical >=65 years	70 Participants n=93 Participants	78 Participants n=4 Participants	70 Participants n=27 Participants	218 Participants n=483 Participants
Age Continuous	63.9 years STANDARD_DEVIATION 7.8 • n=93 Participants	65.4 years STANDARD_DEVIATION 9.0 • n=4 Participants	63.8 years STANDARD_DEVIATION 8.6 • n=27 Participants	64.4 years STANDARD_DEVIATION 8.5 • n=483 Participants
Sex: Female, Male Female	64 Participants n=93 Participants	52 Participants n=4 Participants	56 Participants n=27 Participants	172 Participants n=483 Participants
Sex: Female, Male Male	83 Participants n=93 Participants	97 Participants n=4 Participants	91 Participants n=27 Participants	271 Participants n=483 Participants
Region of Enrollment United States	147 participants n=93 Participants	149 participants n=4 Participants	147 participants n=27 Participants	443 participants n=483 Participants
# Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in 30 days prior to screening 0 exacerbations	146 participants n=93 Participants	147 participants n=4 Participants	145 participants n=27 Participants	438 participants n=483 Participants
# Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in 30 days prior to screening 1 exacerbation	1 participants n=93 Participants	2 participants n=4 Participants	1 participants n=27 Participants	4 participants n=483 Participants
# Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in 30 days prior to screening 2 exacerbations	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
# Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in 30 days prior to screening >2 exacerbations	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants
# Packs Currently Smoked Per Day 0 packs per day	72 participants n=93 Participants	89 participants n=4 Participants	82 participants n=27 Participants	243 participants n=483 Participants
# Packs Currently Smoked Per Day >0 - <=1 packs per day	59 participants n=93 Participants	38 participants n=4 Participants	44 participants n=27 Participants	141 participants n=483 Participants
# Packs Currently Smoked Per Day >1 - <=2 packs per day	14 participants n=93 Participants	21 participants n=4 Participants	17 participants n=27 Participants	52 participants n=483 Participants
# Packs Currently Smoked Per Day >2 - <=4 packs per day	2 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants	7 participants n=483 Participants
# Packs Currently Smoked Per Day >4 packs per day	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
Number of Pack-Years Smoked < 15 pack years smoked	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
Number of Pack-Years Smoked >= 15 - < 25 pack years smoked	8 participants n=93 Participants	13 participants n=4 Participants	13 participants n=27 Participants	34 participants n=483 Participants
Number of Pack-Years Smoked >= 25 - < 30 pack years smoked	10 participants n=93 Participants	10 participants n=4 Participants	11 participants n=27 Participants	31 participants n=483 Participants
Number of Pack-Years Smoked >= 30 pack years smoked	129 participants n=93 Participants	126 participants n=4 Participants	123 participants n=27 Participants	378 participants n=483 Participants
Oral or Inhaled Steroid Use Yes	52 participants n=93 Participants	59 participants n=4 Participants	59 participants n=27 Participants	170 participants n=483 Participants
Oral or Inhaled Steroid Use No	95 participants n=93 Participants	90 participants n=4 Participants	88 participants n=27 Participants	273 participants n=483 Participants
Race/Ethnicity Asian	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
Race/Ethnicity Black or African American	19 participants n=93 Participants	21 participants n=4 Participants	23 participants n=27 Participants	63 participants n=483 Participants
Race/Ethnicity Caucasian	127 participants n=93 Participants	126 participants n=4 Participants	122 participants n=27 Participants	375 participants n=483 Participants
Race/Ethnicity Hispanic	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants	4 participants n=483 Participants
Race/Ethnicity Other	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Baseline Dyspnea Index	5.34 units on a scale STANDARD_DEVIATION 1.72 • n=93 Participants	5.34 units on a scale STANDARD_DEVIATION 2.18 • n=4 Participants	5.10 units on a scale STANDARD_DEVIATION 2.38 • n=27 Participants	5.26 units on a scale STANDARD_DEVIATION 2.09 • n=483 Participants
Forced Expiratory Volume (FEV1)	1.210 Liter STANDARD_DEVIATION 0.420 • n=93 Participants	1.222 Liter STANDARD_DEVIATION 0.465 • n=4 Participants	1.204 Liter STANDARD_DEVIATION 0.422 • n=27 Participants	1.212 Liter STANDARD_DEVIATION 0.435 • n=483 Participants
Percent Predicted Forced Expiratory Volume (FEV1)	41.19 percent predicted FEV1 STANDARD_DEVIATION 11.52 • n=93 Participants	40.87 percent predicted FEV1 STANDARD_DEVIATION 13.59 • n=4 Participants	40.22 percent predicted FEV1 STANDARD_DEVIATION 12.22 • n=27 Participants	40.76 percent predicted FEV1 STANDARD_DEVIATION 12.46 • n=483 Participants

PRIMARY outcome

Timeframe: Six months

Population: ITT Population

Percent of participants with the adverse event specified.

SOC = system organ class.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any AE	66.7 percent of participants	67.8 percent of participants	76.2 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any Severe AE	10.9 percent of participants	13.4 percent of participants	11.6 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any Potentially Related AE	34.7 percent of participants	32.9 percent of participants	34.7 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any Beta-Mediated AE	17.0 percent of participants	10.7 percent of participants	15.6 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any AE w SOC of Cardiac Disorders	6.1 percent of participants	6.0 percent of participants	6.1 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any Serious AE	9.5 percent of participants	13.4 percent of participants	6.8 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any AE Leading to Discontinuation	8.2 percent of participants	10.1 percent of participants	12.2 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any COPD Exacerbation (Protocol Definition)	22.4 percent of participants	32.2 percent of participants	30.6 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any COPD Exacerbation (Expanded Definition)	27.9 percent of participants	35.6 percent of participants	38.1 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any Ischaemic AE	1.4 percent of participants	0.7 percent of participants	5.4 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any Arrhythmnic AE	3.4 percent of participants	3.4 percent of participants	1.4 percent of participants
Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Any AE w SOC Respiratory, Thoracic, & Mediastinal	27.2 percent of participants	34.2 percent of participants	34.0 percent of participants

SECONDARY outcome

Timeframe: Visit 6 (week 27)

Population: ITT Population

New holter monitoring alerts are defined as those alerts that occurred post-randomization and were not present at baseline.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With New 24-Hour Holter Monitoring Alerts	15 Participants	19 Participants	9 Participants

SECONDARY outcome

Timeframe: visit 6 (week 27)

Population: ITT Population

Patients with glucose values that met low (<=40 mg/dL) or high (>=175 mg/dL) criteria were considered potentially clinically significant.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With Potentially Clinically Significant Glucose Evaluations <=40 mg/dL	1 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Glucose Evaluations >=175 mg/dL	20 Participants	55 Participants	54 Participants

SECONDARY outcome

Timeframe: visit 6 (week 27)

Population: ITT Population

Patients with potassium values that met low (<=3 mEq/L) or high (>=6 mEq/L) criteria were considered potentially clinically significant.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With Potentially Clinically Significant Potassium Evaluations <= 3mEq/L	2 Participants	4 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Potassium Evaluations >= 6mEq/L	4 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: visit 6 (week 27)

Population: ITT Population

New Electrocardiogram (ECG) alerts are defined as those alerts that occurred post-treatment and were not present at baseline.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With New 12-Lead Electrocardiogram (ECG) Alerts	1 Participants	1 Participants	5 Participants

SECONDARY outcome

Timeframe: weeks 0,3,13,26

Population: ITT Population This outcome was added as an amendment after the study was initiated; therefore approximately half of the ITT population had these assessments at baseline. An available cases analysis was performed with no imputation for missing data.

Mean Change in Inspiratory Capacity values from baseline (baseline assessment obtained at Visit 2, pre-dose). Spirometry measurements collected within 6 hours following in-clinic rescue/supplemental medications use were excluded from analysis.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Inspiratory Capacity Changes From Baseline Visit 3 (wk 3): Pre-Dose n=74,77,69	0.058 Liter 95% Confidence Interval 0.380 • Interval -0.03 to 0.146	0.032 Liter 95% Confidence Interval 0.409 • Interval -0.06 to 0.125	0.124 Liter 95% Confidence Interval 0.370 • Interval 0.035 to 0.212
Inspiratory Capacity Changes From Baseline Visit 3 (wk 3): 2 hours Post-dose n=75,75,69	0.206 Liter 95% Confidence Interval 0.410 • Interval 0.111 to 0.3	0.241 Liter 95% Confidence Interval 0.401 • Interval 0.149 to 0.333	0.331 Liter 95% Confidence Interval 0.448 • Interval 0.223 to 0.438
Inspiratory Capacity Changes From Baseline Visit 4 (wk 13): Pre-Dose n=62,63,58	0.114 Liter 95% Confidence Interval 0.368 • Interval 0.02 to 0.207	0.005 Liter 95% Confidence Interval 0.441 • Interval -0.106 to 0.116	0.124 Liter 95% Confidence Interval 0.447 • Interval 0.006 to 0.242
Inspiratory Capacity Changes From Baseline Visit 4 (wk 13): 2 hours Post-Dose n=60,63,58	0.290 Liter 95% Confidence Interval 0.445 • Interval 0.174 to 0.405	0.233 Liter 95% Confidence Interval 0.364 • Interval 0.141 to 0.325	0.284 Liter 95% Confidence Interval 0.423 • Interval 0.173 to 0.395
Inspiratory Capacity Changes From Baseline Visit 5 (wk 26): Pre-Dose n=58,58,53	0.039 Liter 95% Confidence Interval 0.354 • Interval -0.054 to 0.132	0.057 Liter 95% Confidence Interval 0.326 • Interval -0.029 to 0.142	0.154 Liter 95% Confidence Interval 0.371 • Interval 0.051 to 0.256
Inspiratory Capacity Changes From Baseline Visit 5 (wk 26): 2 hours Post-Dose n=58,58,53	0.234 Liter 95% Confidence Interval 0.451 • Interval 0.116 to 0.353	0.202 Liter 95% Confidence Interval 0.402 • Interval 0.097 to 0.308	0.368 Liter 95% Confidence Interval 0.443 • Interval 0.245 to 0.49
Inspiratory Capacity Changes From Baseline Visit 2 (wk 0): 2 hours Post-dose n=79,85,80	0.240 Liter 95% Confidence Interval 0.363 • Interval 0.158 to 0.321	0.297 Liter 95% Confidence Interval 0.300 • Interval 0.232 to 0.361	0.330 Liter 95% Confidence Interval 0.354 • Interval 0.251 to 0.408

SECONDARY outcome

Timeframe: weeks 0,3,13,26

Population: ITT population. An available cases analysis was performed with no imputation for missing data.

The 6 hour peak change from baseline is the maximum of the post-dose change values through 6 hours at each visit.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) Visit 2 (week 0) n=147,149,147	0.294 Liter 95% Confidence Interval 0.210 • Interval 0.26 to 0.328	0.314 Liter 95% Confidence Interval 0.189 • Interval 0.284 to 0.345	0.357 Liter 95% Confidence Interval 0.218 • Interval 0.321 to 0.392
6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) Visit 3 (week 3) n=133,133,131	0.280 Liter 95% Confidence Interval 0.229 • Interval 0.241 to 0.319	0.305 Liter 95% Confidence Interval 0.211 • Interval 0.269 to 0.341	0.334 Liter 95% Confidence Interval 0.230 • Interval 0.294 to 0.374
6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) Visit 4 (week 13) n=117,112,111	0.251 Liter 95% Confidence Interval 0.223 • Interval 0.21 to 0.291	0.316 Liter 95% Confidence Interval 0.236 • Interval 0.271 to 0.36	0.323 Liter 95% Confidence Interval 0.222 • Interval 0.281 to 0.365
6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) Visit 5 (week 26) n=108,100,103	0.264 Liter 95% Confidence Interval 0.230 • Interval 0.22 to 0.308	0.302 Liter 95% Confidence Interval 0.239 • Interval 0.255 to 0.349	0.343 Liter 95% Confidence Interval 0.224 • Interval 0.299 to 0.387

SECONDARY outcome

Timeframe: visit 6 (week 27)

Number of subjects with a heart rate that was lower/higher than a set limit and increased/decreased from set baseline limit in beats per minute (bpm)

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With Potentially Clinically Significant Heart Rate < 120 bpm & >= 25 bpm	2 Participants	1 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Heart Rate < 50 bpm & >= 15 bpm	6 Participants	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)

Population: ITT Population

Supplemental medication usage is recorded throughout the study. MDI stands for metered dose inhaler.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Days Used Per Week Screening Period (day -14 to day 0 pre-dose)	4.10 Days Used / Week 95% Confidence Interval 2.92 • Interval 3.62 to 4.57	3.73 Days Used / Week 95% Confidence Interval 2.95 • Interval 3.25 to 4.21	3.84 Days Used / Week 95% Confidence Interval 2.92 • Interval 3.36 to 4.31
Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Days Used Per Week Visits 2-5 (week 0 - 26)	2.66 Days Used / Week 95% Confidence Interval 2.63 • Interval 2.33 to 3.09	2.36 Days Used / Week 95% Confidence Interval 2.60 • Interval 1.94 to 2.78	2.52 Days Used / Week 95% Confidence Interval 2.66 • Interval 2.09 to 2.96

SECONDARY outcome

Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)

Population: ITT Population

Supplemental medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day Visits 2-5 (week 0 - 26)	1.61 Actuations / Day 95% Confidence Interval 2.28 • Interval 1.24 to 1.98	1.59 Actuations / Day 95% Confidence Interval 2.37 • Interval 1.21 to 1.97	1.58 Actuations / Day 95% Confidence Interval 2.12 • Interval 1.24 to 1.93
Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day Screening period (day -14 to day 0 pre-dose)	2.70 Actuations / Day 95% Confidence Interval 2.72 • Interval 2.25 to 3.14	2.43 Actuations / Day 95% Confidence Interval 2.69 • Interval 1.99 to 2.86	2.67 Actuations / Day 95% Confidence Interval 3.06 • Interval 2.18 to 3.17

SECONDARY outcome

Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)

Population: ITT Population

Rescue medication usage during the study. MDI stands for metered dose inhaler.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Days Used Per Week Screening Period (day -14 to day 0 pre-dose)	4.18 Days Used / Week 95% Confidence Interval 2.85 • Interval 3.72 to 4.65	4.20 Days Used / Week 95% Confidence Interval 2.86 • Interval 3.74 to 4.66	4.23 Days Used / Week 95% Confidence Interval 2.77 • Interval 3.78 to 4.69
Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Days Used Per Week Visits 2-5 (week 0 - 26)	2.85 Days Used / Week 95% Confidence Interval 2.64 • Interval 2.42 to 3.28	2.44 Days Used / Week 95% Confidence Interval 2.49 • Interval 2.03 to 2.84	2.75 Days Used / Week 95% Confidence Interval 2.64 • Interval 2.32 to 3.18

SECONDARY outcome

Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)

Population: ITT Population

Rescue medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day Visits 2-5 (week 0 - 26)	1.71 Actuations/Day 95% Confidence Interval 2.27 • Interval 1.34 to 2.08	1.56 Actuations/Day 95% Confidence Interval 2.32 • Interval 1.18 to 1.93	1.65 Actuations/Day 95% Confidence Interval 2.11 • Interval 1.31 to 2.0
Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day Screening Period (day -14 to day 0 pre-dose)	2.91 Actuations/Day 95% Confidence Interval 2.80 • Interval 2.45 to 3.37	2.68 Actuations/Day 95% Confidence Interval 2.57 • Interval 2.27 to 3.1	2.97 Actuations/Day 95% Confidence Interval 3.05 • Interval 2.47 to 3.47

SECONDARY outcome

Timeframe: weeks 0,3,13,26

Population: ITT Population. Spirometry measurements collected within 6 hours following in-clinic rescue/supplemental medications use were excluded from analysis.

Area under the change from baseline curve from 0 to 6 hours. Time-normalized AUC (0-6 hrs) was derived using the linear trapezoidal method.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline Visit 2 (week 0) n=147,149,147	0.191 Liter 95% Confidence Interval 0.172 • Interval 0.163 to 0.219	0.216 Liter 95% Confidence Interval 0.157 • Interval 0.191 to 0.242	0.253 Liter 95% Confidence Interval 0.179 • Interval 0.224 to 0.282
Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline Visit 4 (week 13) n=113,110,110	0.155 Liter 95% Confidence Interval 0.210 • Interval 0.116 to 0.194	0.214 Liter 95% Confidence Interval 0.225 • Interval 0.171 to 0.256	0.218 Liter 95% Confidence Interval 0.214 • Interval 0.177 to 0.258
Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline Visit 5 (week 26) n=107,100,101	0.161 Liter 95% Confidence Interval 0.209 • Interval 0.121 to 0.201	0.197 Liter 95% Confidence Interval 0.229 • Interval 0.152 to 0.243	0.241 Liter 95% Confidence Interval 0.209 • Interval 0.2 to 0.282
Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline Visit 3 (week 3) n=129,129,131	0.175 Liter 95% Confidence Interval 0.204 • Interval 0.139 to 0.21	0.208 Liter 95% Confidence Interval 0.200 • Interval 0.173 to 0.243	0.224 Liter 95% Confidence Interval 0.206 • Interval 0.188 to 0.259

SECONDARY outcome

Timeframe: weeks 13, 26

Population: ITT Population

The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A Transitional Dyspnea Index score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Transitional (Relative Change in) Dyspnea Index Visit 4 (week 13) n=115,113,114	1.50 units on a scale 95% Confidence Interval 2.40 • Interval 1.05 to 1.94	1.47 units on a scale 95% Confidence Interval 2.56 • Interval 0.99 to 1.95	1.56 units on a scale 95% Confidence Interval 2.74 • Interval 1.05 to 2.07
Transitional (Relative Change in) Dyspnea Index Visit 5 (week 26) n=108,102,103	1.44 units on a scale 95% Confidence Interval 2.77 • Interval 0.92 to 1.97	1.43 units on a scale 95% Confidence Interval 2.83 • Interval 0.88 to 1.99	1.49 units on a scale 95% Confidence Interval 2.76 • Interval 0.95 to 2.02

SECONDARY outcome

Timeframe: weeks 13, 26

Population: ITT Population. Visit 4 n=115,113,114 Visit 5 n=108,102,103

The number of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score compares current health against baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With an Improved Transitional Dyspnea Index >= 1Unit Improvement, visit 4 (wk13) n=115,113,114	59 Participants	59 Participants	61 Participants
Number of Participants With an Improved Transitional Dyspnea Index >= 1 Unit Improvement,visit 5(wk 26) n=108,102,103	56 Participants	49 Participants	54 Participants

SECONDARY outcome

Timeframe: weeks 0,3,13,26

Population: ITT Population

The 24 hour trough is the FEV1 value obtained 24 hours post first dose. This value is compared to the baseline FEV1 value.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) Visit 3 (week 3) n=130,130,127	0.096 Liters 95% Confidence Interval 0.192 • Interval 0.063 to 0.13	0.124 Liters 95% Confidence Interval 0.209 • Interval 0.088 to 0.161	0.131 Liters 95% Confidence Interval 0.201 • Interval 0.096 to 0.167
Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) Visit 4 (week 13) n=111,108,110	0.094 Liters 95% Confidence Interval 0.192 • Interval 0.058 to 0.13	0.116 Liters 95% Confidence Interval 0.187 • Interval 0.08 to 0.152	0.101 Liters 95% Confidence Interval 0.207 • Interval 0.062 to 0.14
Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) Visit 2 (week 0) n=141,143,141	0.162 Liters 95% Confidence Interval 0.209 • Interval 0.127 to 0.197	0.172 Liters 95% Confidence Interval 0.206 • Interval 0.138 to 0.206	0.155 Liters 95% Confidence Interval 0.226 • Interval 0.117 to 0.192
Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) Visit 5 (week 26) n=105,97,101	0.087 Liters 95% Confidence Interval 0.215 • Interval 0.046 to 0.129	0.098 Liters 95% Confidence Interval 0.243 • Interval 0.049 to 0.147	0.137 Liters 95% Confidence Interval 0.229 • Interval 0.091 to 0.182

SECONDARY outcome

Timeframe: weeks 13, 26

Population: ITT Population

The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1=much better and 7=much worse. Ratings were assessed relative to the subject's initial entry into the study.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Subject Global Evaluations Change From Baseline Visit 4 (week 13) n=112,112,114	-0.96 units on a scale 95% Confidence Interval 1.39 • Interval -1.23 to -0.7	-1.11 units on a scale 95% Confidence Interval 1.51 • Interval -1.39 to -0.82	-0.89 units on a scale 95% Confidence Interval 1.49 • Interval -1.16 to -0.61
Subject Global Evaluations Change From Baseline Visit 5 (week 26) n=106,102,102	-0.97 units on a scale 95% Confidence Interval 1.50 • Interval -1.26 to -0.68	-1.06 units on a scale 95% Confidence Interval 1.41 • Interval -1.33 to -0.78	-0.83 units on a scale 95% Confidence Interval 1.70 • Interval -1.17 to -0.5

SECONDARY outcome

Timeframe: weeks 13, 26

Population: ITT Population

The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. Ratings were assessed relative to the subject's initial entry into the study.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Investigator Global Evaluations Change From Baseline Visit 4 (week 13) n=111,112,110	-0.66 units on a scale 95% Confidence Interval 1.27 • Interval -0.9 to -0.42	-0.88 units on a scale 95% Confidence Interval 1.27 • Interval -1.11 to -0.64	-0.75 units on a scale 95% Confidence Interval 1.43 • Interval -1.02 to -0.48
Investigator Global Evaluations Change From Baseline Visit 5 (week 26) n=106,100,100	-0.74 units on a scale 95% Confidence Interval 1.20 • Interval -0.97 to -0.51	-0.74 units on a scale 95% Confidence Interval 1.28 • Interval -0.99 to -0.49	-0.76 units on a scale 95% Confidence Interval 1.65 • Interval -1.09 to -0.43

SECONDARY outcome

Timeframe: Baseline (visit 2), weeks 13, 26

Population: ITT Population

The BODE index (0=relative health and 10=severe chronic obstructive pulmonary disease) is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the 6-minute walk test. Scores were derived using pre-dose assessments from each visit.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
BODE Index Visit 2 (baseline- week 0) n=146,148,147	4.82 units on a scale Standard Deviation 1.58	4.98 units on a scale Standard Deviation 1.64	5.14 units on a scale Standard Deviation 1.73
BODE Index Visit 4 (week 13) n=110,108,109	4.22 units on a scale Standard Deviation 2.03	3.97 units on a scale Standard Deviation 1.90	4.28 units on a scale Standard Deviation 1.95
BODE Index Visit 5 (week 26) n=103,100,101	3.92 units on a scale Standard Deviation 1.91	3.94 units on a scale Standard Deviation 1.99	4.11 units on a scale Standard Deviation 2.20

SECONDARY outcome

Timeframe: Post-Dose weeks 0, 13, 26

Population: ITT Population

Mean change from baseline in distance walked (meters)

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
6-Minute Walk: Change From Baseline in the Distance Walked in 6 Minutes Visit 2 (week 0 - post dose) n=146,148,146	15.28 meters 95% Confidence Interval 81.22 • Interval 2.0 to 28.56	15.72 meters 95% Confidence Interval 67.59 • Interval 4.74 to 26.7	12.37 meters 95% Confidence Interval 69.65 • Interval 0.97 to 23.76
6-Minute Walk: Change From Baseline in the Distance Walked in 6 Minutes Visit 4 (week 13 - post dose) n=116,110,112	16.05 meters 95% Confidence Interval 104.90 • Interval -3.24 to 35.34	4.13 meters 95% Confidence Interval 128.01 • Interval -20.06 to 28.32	31.07 meters 95% Confidence Interval 77.20 • Interval 16.61 to 45.52
6-Minute Walk: Change From Baseline in the Distance Walked in 6 Minutes Visit 5 (week 26 - post dose) n=106,97,103	24.42 meters 95% Confidence Interval 94.19 • Interval 6.28 to 42.56	1.24 meters 95% Confidence Interval 135.05 • Interval -25.98 to 28.46	37.00 meters 95% Confidence Interval 85.01 • Interval 20.38 to 53.61

SECONDARY outcome

Timeframe: weeks 13, 26

Population: ITT Population

Scores are expressed as a mean change from baseline of overall impairment (total score). The questionnaire has a scale of 100 which represents worst possible health status to 0 which indicates best possible health status.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Change From Baseline in St. George's Respiratory Questionnaire Visit 4 (week 13) n=105,102,105	-4.16 units on a scale 95% Confidence Interval 10.09 • Interval -6.11 to -2.21	-3.44 units on a scale 95% Confidence Interval 12.10 • Interval -5.81 to -1.06	-1.92 units on a scale 95% Confidence Interval 9.86 • Interval -3.82 to -0.01
Mean Change From Baseline in St. George's Respiratory Questionnaire Visit 5 (week 26) n=97,94,97	-6.76 units on a scale 95% Confidence Interval 10.06 • Interval -8.78 to -4.73	-3.73 units on a scale 95% Confidence Interval 13.14 • Interval -6.42 to -1.04	-3.68 units on a scale 95% Confidence Interval 11.78 • Interval -6.06 to -1.31

SECONDARY outcome

Timeframe: Visit 4 (week 13) , Visit 5 (week 26)

Population: ITT Population

Scores are expressed as the number of participants with >= 4 unit improvement in overall impairment (total score), where 100 represents worst possible health status and 0 indicates best possible health status.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Number of Participants With a >=4 Unit Improvement on the St. George's Respiratory Questionnaire Visit 4 (week 13) n=105,102,105	49 Participants	47 Participants	39 Participants
Number of Participants With a >=4 Unit Improvement on the St. George's Respiratory Questionnaire Visit 5 (week 26) n=97,94,97	55 Participants	43 Participants	42 Participants

SECONDARY outcome

Timeframe: Baseline (visit 2), weeks 13, 26

Population: ITT Population

Scores range from 0 to 4, with a score of 4 indicating that a subject is too breathless to leave the house or becomes breathless when dressing or undressing. The highest numbered question to which the subject answered 'Yes' is the Dyspnea Scale Score.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Modified Medical Research Council Dyspnea Questionaire Visit 4 (week 13) n=117,113,115	2.35 units on a scale Standard Deviation 1.03	2.10 units on a scale Standard Deviation 1.05	2.43 units on a scale Standard Deviation 1.21
Modified Medical Research Council Dyspnea Questionaire Visit 5 (week 26) n=107,103,103	2.16 units on a scale Standard Deviation 1.10	2.09 units on a scale Standard Deviation 1.14	2.26 units on a scale Standard Deviation 1.26
Modified Medical Research Council Dyspnea Questionaire Baseline (visit 2, week 0) n=147,149,145	2.73 units on a scale Standard Deviation 0.78	2.76 units on a scale Standard Deviation 0.79	2.91 units on a scale Standard Deviation 0.81
Modified Medical Research Council Dyspnea Questionaire Visit 3 (week 3) n=132,131,128	2.33 units on a scale Standard Deviation 1.02	2.47 units on a scale Standard Deviation 0.96	2.50 units on a scale Standard Deviation 1.12

SECONDARY outcome

Timeframe: visits 4 (week 13), visit 5 (week 26)

Population: ITT population. Percentages were based on the number of subjects with non-missing data. Visit 4 n=115, 113, 114 Visit 5 n=108, 102, 103

The percentage of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score is the sum of the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Percent (%) of Participants With an Improved Transitional Dyspnea Index >=1 Unit Improvement,visit 4 (wk 13) n=115,113,114	51.3 percent of participants	52.2 percent of participants	53.5 percent of participants
Percent (%) of Participants With an Improved Transitional Dyspnea Index >=1 Unit Improvement,visit 5 (wk 26) n=108,102,103	51.9 percent of participants	48.0 percent of participants	52.4 percent of participants

SECONDARY outcome

Timeframe: visit 4 (week 13), visit 5 (week 26)

Population: ITT population

Percent of participants with a >=4 unit improvement in the overall impairment (total score) of the St. George's Respiratory Questionaire. This questionaire uses a 100 - 0 scale, where 100 represents the worst possible health status and 0 indicates the best possible health status.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Percent (%) of Participants With a >=4 Unit Improvement in the St. George's Respiratory Questionaire Visit 5 (week 26), n=97,94,97	56.7 percent of participants	45.7 percent of participants	43.3 percent of participants
Percent (%) of Participants With a >=4 Unit Improvement in the St. George's Respiratory Questionaire Visit 4 (week 13), n=105,102,105	46.7 percent of participants	46.1 percent of participants	37.1 percent of participants

SECONDARY outcome

Timeframe: Baseline (Visit 2), week 13, week 26

Population: ITT population

This test measures the participants' level of fitness. It is a measure of the distance the participant can walk in 6 minutes.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Visit 5 (week 26) Pre-Dose n=105, 100, 103	355.83 meters Standard Deviation 181.84	338.21 meters Standard Deviation 129.68	337.25 meters Standard Deviation 167.83
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Visit 5 (week 26) Post-Dose n=106, 98, 103	361.72 meters Standard Deviation 169.96	344.98 meters Standard Deviation 122.38	348.11 meters Standard Deviation 174.38
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Visit 2 (week 0) Pre-Dose n=147, 148, 147	334.84 meters Standard Deviation 155.43	315.94 meters Standard Deviation 131.74	328.36 meters Standard Deviation 183.44
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Visit 2 (week 0) Post-Dose n=146, 149, 146	352.19 meters Standard Deviation 163.27	332.80 meters Standard Deviation 135.79	339.81 meters Standard Deviation 194.09
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Visit 4 (week 13) Pre-Dose n=115, 111, 111	344.95 meters Standard Deviation 175.53	332.25 meters Standard Deviation 140.60	333.63 meters Standard Deviation 150.55
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Visit 4 (week 13) Post-Dose n=116, 111, 112	352.51 meters Standard Deviation 167.90	337.28 meters Standard Deviation 165.02	337.68 meters Standard Deviation 155.65

SECONDARY outcome

Timeframe: Baseline (Visit 2), Weeks 13, 26

Population: ITT population

The investigator global evaluation is reported by the study investigator. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Values for Investigator Global Evaluations Visit 2 (Baseline, Week 0) n=145,148,144	3.73 units on a scale Standard Deviation 0.88	3.88 units on a scale Standard Deviation 0.77	3.84 units on a scale Standard Deviation 1.06
Mean Values for Investigator Global Evaluations Visit 4 (week 13) n=113,112,112	3.12 units on a scale Standard Deviation 1.05	3.04 units on a scale Standard Deviation 1.17	3.04 units on a scale Standard Deviation 1.14
Mean Values for Investigator Global Evaluations Visit 5 (week 26) n=107,100,102	3.08 units on a scale Standard Deviation 1.04	3.16 units on a scale Standard Deviation 1.28	3.01 units on a scale Standard Deviation 1.16

SECONDARY outcome

Timeframe: Baseline (Visit 2), weeks 13, 26

Population: ITT population

A questionnaire to assess respiratory health. Scores are expressed as a percentage of overall impairment (total score), where 100 represents the worst possible health status and 0 indicates best possible health status.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Values for St. George's Respiratory Questionnaire Visit 4 (week 13) n=114, 105, 108	43.48 units on a scale Standard Deviation 16.53	43.64 units on a scale Standard Deviation 18.94	49.95 units on a scale Standard Deviation 19.67
Mean Values for St. George's Respiratory Questionnaire Visit 5 (week 26) n=105, 97, 99	41.72 units on a scale Standard Deviation 16.35	42.69 units on a scale Standard Deviation 17.98	48.09 units on a scale Standard Deviation 20.68
Mean Values for St. George's Respiratory Questionnaire Visit 2 (Baseline; week 0) n=136,141,144	48.86 units on a scale Standard Deviation 14.90	49.36 units on a scale Standard Deviation 17.38	52.40 units on a scale Standard Deviation 17.71

SECONDARY outcome

Timeframe: Baseline (Visit 2), weeks 13, 26

Population: ITT Population

The subject global evaluation is reported by study subjects/participants. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Values for Subject Global Evaluations Visit 2 (baseline; week 0) n=145, 148, 146	3.73 units on a scale Standard Deviation 1.08	3.97 units on a scale Standard Deviation 1.08	3.86 units on a scale Standard Deviation 1.05
Mean Values for Subject Global Evaluations Visit 4 (week 13) n=114, 113, 115	2.83 units on a scale Standard Deviation 1.09	2.88 units on a scale Standard Deviation 1.26	2.94 units on a scale Standard Deviation 1.32
Mean Values for Subject Global Evaluations Visit 5 (week 26) n=108, 103, 103	2.86 units on a scale Standard Deviation 1.31	2.96 units on a scale Standard Deviation 1.32	2.94 units on a scale Standard Deviation 1.36

SECONDARY outcome

Timeframe: Baseline (Visit 2), Weeks 3, 13, 26

Inspiratory capacity is the maximum volume that can be inhaled.

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Values for Inspiratory Capacity Visit 4 (wk 13) pre-dose; n=100,94,99	1.874 Liters Standard Deviation 0.676	1.890 Liters Standard Deviation 0.656	1.962 Liters Standard Deviation 0.640
Mean Values for Inspiratory Capacity Visit 5 (wk 26) pre-dose; n=106,101,101	1.817 Liters Standard Deviation 0.620	1.901 Liters Standard Deviation 0.630	2.070 Liters Standard Deviation 0.691
Mean Values for Inspiratory Capacity Visit 5 (wk 26) post dose; n=105,100,101	1.978 Liters Standard Deviation 0.690	2.084 Liters Standard Deviation 0.613	2.273 Liters Standard Deviation 0.692
Mean Values for Inspiratory Capacity Visit 2 (wk 0, baseline) pre-dose; n=80,86,82	1.739 Liters Standard Deviation 0.630	1.864 Liters Standard Deviation 0.551	1.764 Liters Standard Deviation 0.577
Mean Values for Inspiratory Capacity Visit 3 (wk 3) pre-dose; n=81,83,74	1.826 Liters Standard Deviation 0.654	1.889 Liters Standard Deviation 0.558	1.909 Liters Standard Deviation 0.633
Mean Values for Inspiratory Capacity Visit 2 (wk 0, baseline) post dose; n=80,85,81	1.976 Liters Standard Deviation 0.730	2.161 Liters Standard Deviation 0.624	2.109 Liters Standard Deviation 0.610
Mean Values for Inspiratory Capacity VIsit 3 (wk 3) post dose; n=82,81,74	1.973 Liters Standard Deviation 0.685	2.111 Liters Standard Deviation 0.627	2.108 Liters Standard Deviation 0.632
Mean Values for Inspiratory Capacity Visit 4 (wk 13) post dose; n=98,94,99	2.089 Liters Standard Deviation 0.729	2.081 Liters Standard Deviation 0.658	2.176 Liters Standard Deviation 0.692

SECONDARY outcome

Timeframe: Baseline (Visit 2), weeks 3, 13, 26

Forced Expiratory Volume in one second

Outcome measures

Measure	Formoterol 12 Mcg 2x/Day n=147 Participants	Arformoterol 15 Mcg 2x/Day n=149 Participants	Arformoterol 25 Mcg 2x/Day n=147 Participants
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 2 (wk 0, baseline) pre dose; n=147,149,147	1.210 Liters Standard Deviation 0.420	1.222 Liters Standard Deviation 0.465	1.204 Liters Standard Deviation 0.422
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 4 (wk 13) 24 hr; n=111,108,110	1.316 Liters Standard Deviation 0.461	1.331 Liters Standard Deviation 0.460	1.294 Liters Standard Deviation 0.444
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 5 (wk 26) pre dose; n=107,102,101	1.283 Liters Standard Deviation 0.466	1.291 Liters Standard Deviation 0.453	1.325 Liters Standard Deviation 0.451
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 5 (wk 26) 24 hr; n=105,97,101	1.296 Liters Standard Deviation 0.455	1.314 Liters Standard Deviation 0.467	1.360 Liters Standard Deviation 0.468
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 2 (wk 0) 6 hr; n=142,145,138	1.383 Liters Standard Deviation 0.511	1.410 Liters Standard Deviation 0.533	1.428 Liters Standard Deviation 0.479
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 3 (wk 3) 6 hr; n=130,125,127	1.338 Liters Standard Deviation 0.464	1.386 Liters Standard Deviation 0.504	1.386 Liters Standard Deviation 0.484
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 4 (wk 13) 6 hr; n=109,109,104	1.339 Liters Standard Deviation 0.487	1.385 Liters Standard Deviation 0.482	1.361 Liters Standard Deviation 0.463
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 2 (wk 0) 24 hr; n=141,143,141	1.378 Liters Standard Deviation 0.497	1.400 Liters Standard Deviation 0.545	1.360 Liters Standard Deviation 0.470
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 3 (wk 3) pre dose; n=129,129,132	1.311 Liters Standard Deviation 0.458	1.323 Liters Standard Deviation 0.484	1.327 Liters Standard Deviation 0.477
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 3 (wk 3) 24 hr; n=130,130,127	1.310 Liters Standard Deviation 0.456	1.346 Liters Standard Deviation 0.490	1.355 Liters Standard Deviation 0.475
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visit 4 (wk 13) pre dose; n=113,111,111	1.281 Liters Standard Deviation 0.470	1.310 Liters Standard Deviation 0.483	1.308 Liters Standard Deviation 0.473
Mean Values for Forced Expiratory Volume in One Second (FEV1) Visti 5 (wk 26) 6 hr; n=101,95,101	1.310 Liters Standard Deviation 0.475	1.355 Liters Standard Deviation 0.457	1.384 Liters Standard Deviation 0.483

Adverse Events

Formoterol 12 Mcg 2x/Day

Serious events: 14 serious events

Other events: 96 other events

Deaths: 0 deaths

Arformoterol 15 Mcg 2x/Day

Serious events: 20 serious events

Other events: 97 other events

Deaths: 0 deaths

Arformoterol 25 Mcg 2x/Day

Serious events: 10 serious events

Other events: 109 other events

Deaths: 0 deaths

Serious adverse events

Measure	Formoterol 12 Mcg 2x/Day	Arformoterol 15 Mcg 2x/Day	Arformoterol 25 Mcg 2x/Day
Cardiac disorders Acute coronary syndrome	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Cardiac disorders Acute myocardial infarction	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Cardiac disorders Angina pectoris	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Cardiac disorders Angina unstable	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Cardiac disorders Atrial fibrillation	0.68% 1/147 • Number of events 1	0.67% 1/149 • Number of events 1	0.68% 1/147 • Number of events 1
Cardiac disorders Atrial flutter	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Cardiac disorders Cardiac failure congestive	0.00% 0/147	1.3% 2/149 • Number of events 2	0.68% 1/147 • Number of events 1
Cardiac disorders Coronary artery disease	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Cardiac disorders Coronary artery thrombosis	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Cardiac disorders Myocardial infarction	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Cardiac disorders Supraventricular tachycardia	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Gastrointestinal disorders Abdominal hernia	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Gastrointestinal disorders Colitis ischaemic	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Gastrointestinal disorders Peritonitis	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Gastrointestinal disorders Umbilical hernia	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Infections and infestations Appendicitis	0.00% 0/147	0.67% 1/149 • Number of events 1	0.68% 1/147 • Number of events 1
Infections and infestations Gasteroenteritis viral	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Infections and infestations Pneumonia	1.4% 2/147 • Number of events 2	2.0% 3/149 • Number of events 3	0.68% 1/147 • Number of events 1
Injury, poisoning and procedural complications Foreign body trauma	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Injury, poisoning and procedural complications Hip fracture	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Injury, poisoning and procedural complications Pneumothorax traumatic	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Injury, poisoning and procedural complications Rib fracture	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Injury, poisoning and procedural complications Stent occlusion	0.00% 0/147	0.00% 0/149	0.68% 1/147 • Number of events 1
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Metabolism and nutrition disorders Dehydration	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/147	1.3% 2/149 • Number of events 2	0.00% 0/147
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma, cell type unspecified, Stage III	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Nervous system disorders Hypoaesthesia	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Nervous system disorders Syncope	0.68% 1/147 • Number of events 1	0.67% 1/149 • Number of events 1	0.00% 0/147
Nervous system disorders Syncope vasovagal	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Renal and urinary disorders Bladder prolapse	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Renal and urinary disorders Renal failure acute	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.4% 5/147 • Number of events 6	4.7% 7/149 • Number of events 7	2.7% 4/147 • Number of events 4
Respiratory, thoracic and mediastinal disorders Diaphragmatic paralysis	0.68% 1/147 • Number of events 1	0.00% 0/149	0.00% 0/147
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/147	0.67% 1/149 • Number of events 1	0.00% 0/147

Other adverse events

Measure	Formoterol 12 Mcg 2x/Day	Arformoterol 15 Mcg 2x/Day	Arformoterol 25 Mcg 2x/Day
Blood and lymphatic system disorders Anemia	0.00% 0/147	2.7% 4/149 • Number of events 4	0.68% 1/147 • Number of events 1
Cardiac disorders Palpitations	2.0% 3/147 • Number of events 4	0.67% 1/149 • Number of events 1	0.00% 0/147
Ear and labyrinth disorders Ear Pain	0.68% 1/147 • Number of events 1	0.00% 0/149	2.0% 3/147 • Number of events 3
Gastrointestinal disorders Abdominal Pain Upper	2.0% 3/147 • Number of events 3	0.67% 1/149 • Number of events 1	0.00% 0/147
Gastrointestinal disorders Constipation	2.7% 4/147 • Number of events 4	1.3% 2/149 • Number of events 2	2.7% 4/147 • Number of events 4
Gastrointestinal disorders Diarrhoea	1.4% 2/147 • Number of events 2	3.4% 5/149 • Number of events 5	1.4% 2/147 • Number of events 2
Gastrointestinal disorders Dry mouth	0.68% 1/147 • Number of events 1	0.67% 1/149 • Number of events 1	2.0% 3/147 • Number of events 3
Gastrointestinal disorders Gastroesophageal reflux disease	2.0% 3/147 • Number of events 3	3.4% 5/149 • Number of events 5	0.68% 1/147 • Number of events 1
Gastrointestinal disorders Nausea	3.4% 5/147 • Number of events 5	1.3% 2/149 • Number of events 2	0.00% 0/147
General disorders Fatigue	2.0% 3/147 • Number of events 3	2.7% 4/149 • Number of events 4	0.68% 1/147 • Number of events 1
General disorders Non-cardiac chest pain	2.0% 3/147 • Number of events 5	0.00% 0/149	0.68% 1/147 • Number of events 1
General disorders Pain	0.00% 0/147	2.7% 4/149 • Number of events 4	0.00% 0/147
General disorders Pyrexia	0.68% 1/147 • Number of events 1	4.0% 6/149 • Number of events 6	2.0% 3/147 • Number of events 3
Infections and infestations Bronchitis	6.1% 9/147 • Number of events 11	5.4% 8/149 • Number of events 12	6.8% 10/147 • Number of events 12
Infections and infestations Diverticulitis	0.00% 0/147	2.7% 4/149 • Number of events 4	0.00% 0/147
Infections and infestations Influenza	2.0% 3/147 • Number of events 3	1.3% 2/149 • Number of events 2	0.68% 1/147 • Number of events 1
Infections and infestations Nasopharyngitis	11.6% 17/147 • Number of events 21	5.4% 8/149 • Number of events 10	10.2% 15/147 • Number of events 21
Infections and infestations Rhinitis	0.68% 1/147 • Number of events 1	2.0% 3/149 • Number of events 3	1.4% 2/147 • Number of events 2
Infections and infestations Sinusitis	2.7% 4/147 • Number of events 6	2.7% 4/149 • Number of events 4	4.8% 7/147 • Number of events 8
Infections and infestations Upper respiratory tract infection	4.1% 6/147 • Number of events 6	2.7% 4/149 • Number of events 6	4.1% 6/147 • Number of events 6
Infections and infestations Viral infection	0.68% 1/147 • Number of events 1	1.3% 2/149 • Number of events 2	2.7% 4/147 • Number of events 6
Metabolism and nutrition disorders Hypokalemia	2.0% 3/147 • Number of events 3	0.67% 1/149 • Number of events 1	0.68% 1/147 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 3/147 • Number of events 3	0.67% 1/149 • Number of events 1	1.4% 2/147 • Number of events 2
Musculoskeletal and connective tissue disorders Back pain	2.7% 4/147 • Number of events 4	2.0% 3/149 • Number of events 3	2.0% 3/147 • Number of events 3
Musculoskeletal and connective tissue disorders Muscle spasms	4.1% 6/147 • Number of events 11	2.7% 4/149 • Number of events 5	4.8% 7/147 • Number of events 8
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.0% 3/147 • Number of events 3	0.67% 1/149 • Number of events 1	0.00% 0/147
Musculoskeletal and connective tissue disorders Pain in extremity	2.7% 4/147 • Number of events 8	1.3% 2/149 • Number of events 2	1.4% 2/147 • Number of events 3
Musculoskeletal and connective tissue disorders Dizziness	4.8% 7/147 • Number of events 8	2.0% 3/149 • Number of events 3	0.68% 1/147 • Number of events 1
Musculoskeletal and connective tissue disorders Headache	2.7% 4/147 • Number of events 6	4.0% 6/149 • Number of events 9	6.8% 10/147 • Number of events 12
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	15.0% 22/147 • Number of events 28	22.8% 34/149 • Number of events 45	23.8% 35/147 • Number of events 43
Respiratory, thoracic and mediastinal disorders Cough	1.4% 2/147 • Number of events 2	0.67% 1/149 • Number of events 1	2.7% 4/147 • Number of events 4
Respiratory, thoracic and mediastinal disorders Dyspnea	1.4% 2/147 • Number of events 2	2.7% 4/149 • Number of events 4	2.0% 3/147 • Number of events 3
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.4% 2/147 • Number of events 2	1.3% 2/149 • Number of events 2	3.4% 5/147 • Number of events 5
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	2.0% 3/147 • Number of events 3	0.67% 1/149 • Number of events 1	0.68% 1/147 • Number of events 1
Vascular disorders Hypertension	2.0% 3/147 • Number of events 3	2.0% 3/149 • Number of events 3	4.1% 6/147 • Number of events 6
Infections and infestations Urinary tract infection	3.4% 5/147 • Number of events 6	2.7% 4/149 • Number of events 6	3.4% 5/147 • Number of events 5
Infections and infestations Candidiasis	2.0% 3/147 • Number of events 4	0.67% 1/149 • Number of events 1	0.68% 1/147 • Number of events 1
Infections and infestations Ear Infection	0.00% 0/147	0.00% 0/149	2.0% 3/147 • Number of events 3
Gastrointestinal disorders Oral Pain	0.68% 1/147 • Number of events 1	0.67% 1/149 • Number of events 1	2.0% 3/147 • Number of events 3

Additional Information

Respiratory Medical Director

Sepracor Inc.

Phone: 1-866-503-6351

Results disclosure agreements

• Principal investigator is a sponsor employee In addition to the \<60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication; if a multicenter publication is not forthcoming within 24 months following completion of study at all sites, the PI shall be free to publish.
• Publication restrictions are in place

Restriction type: OTHER