Trial Outcomes & Findings for Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00424528)

NCT ID: NCT00424528

Last Updated: 2012-06-04

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 235 participants
• Primary outcome timeframe: 24 hours following two weeks of dosing.
• Results posted on: 2012-06-04

Participant Flow

Multicenter (34 sites) study.

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.

Participant milestones

Measure	Arformoterol 15 Mcg Twice Daily Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Overall Study STARTED	76	80	78
Overall Study COMPLETED	71	76	74
Overall Study NOT COMPLETED	5	4	4

Reasons for withdrawal

Measure	Arformoterol 15 Mcg Twice Daily Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Overall Study Adverse Event	2	1	2
Overall Study Protocol Violation	1	1	0
Overall Study Lost to Follow-up	0	1	0
Overall Study noncompliance with study requirements	2	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily	Total n=234 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	47 Participants n=5 Participants	50 Participants n=7 Participants	52 Participants n=5 Participants	149 Participants n=4 Participants
Age, Categorical >=65 years	29 Participants n=5 Participants	30 Participants n=7 Participants	26 Participants n=5 Participants	85 Participants n=4 Participants
Age Continuous	61.6 years STANDARD_DEVIATION 8.4 • n=5 Participants	61.2 years STANDARD_DEVIATION 9.5 • n=7 Participants	62.2 years STANDARD_DEVIATION 7.6 • n=5 Participants	61.7 years STANDARD_DEVIATION 8.5 • n=4 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	37 Participants n=7 Participants	36 Participants n=5 Participants	110 Participants n=4 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	43 Participants n=7 Participants	42 Participants n=5 Participants	124 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) White	71 Participants n=5 Participants	74 Participants n=7 Participants	70 Participants n=5 Participants	215 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	76 participants n=5 Participants	80 participants n=7 Participants	78 participants n=5 Participants	234 participants n=4 Participants
Number of Pack Years Smoked >=15 years to <25 years	0 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants
Number of Pack Years Smoked >=25 years to <=30 years	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Number of Pack Years Smoked >=30 years	72 Participants n=5 Participants	75 Participants n=7 Participants	68 Participants n=5 Participants	215 Participants n=4 Participants
Packs per day currently smoked >0 to 1 pack	24 Participants n=5 Participants	30 Participants n=7 Participants	22 Participants n=5 Participants	76 Participants n=4 Participants
Packs per day currently smoked >1 to 2 packs	22 Participants n=5 Participants	24 Participants n=7 Participants	16 Participants n=5 Participants	62 Participants n=4 Participants
Packs per day currently smoked >2 to 4 packs	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Packs per day currently smoked >4 packs	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Packs per day currently smoked Currently does not smoke	27 Participants n=5 Participants	26 Participants n=7 Participants	39 Participants n=5 Participants	92 Participants n=4 Participants
Baseline Dyspnea Index (BDI) Focal Score	5.8 units on a scale STANDARD_DEVIATION 2.0 • n=5 Participants	5.8 units on a scale STANDARD_DEVIATION 1.9 • n=7 Participants	5.5 units on a scale STANDARD_DEVIATION 2.1 • n=5 Participants	5.7 units on a scale STANDARD_DEVIATION 2.0 • n=4 Participants
Best Forced Expiratory Volume in one second (FEV1)/Best Forced Vital Capacity (FVC) ratio	0.510 Liters STANDARD_DEVIATION 0.098 • n=5 Participants	0.514 Liters STANDARD_DEVIATION 0.107 • n=7 Participants	0.525 Liters STANDARD_DEVIATION 0.108 • n=5 Participants	0.516 Liters STANDARD_DEVIATION 0.104 • n=4 Participants
FEV1	1.366 Liters STANDARD_DEVIATION 0.457 • n=5 Participants	1.377 Liters STANDARD_DEVIATION 0.460 • n=7 Participants	1.350 Liters STANDARD_DEVIATION 0.408 • n=5 Participants	1.365 Liters STANDARD_DEVIATION 0.440 • n=4 Participants
FEV1 Percent Predicted	45.4 percent predicted of FEV1 STANDARD_DEVIATION 11.9 • n=5 Participants	45.7 percent predicted of FEV1 STANDARD_DEVIATION 11.5 • n=7 Participants	44.9 percent predicted of FEV1 STANDARD_DEVIATION 12.0 • n=5 Participants	45.4 percent predicted of FEV1 STANDARD_DEVIATION 11.8 • n=4 Participants
Inspiratory Capacity	2.005 Liters STANDARD_DEVIATION 0.615 • n=5 Participants	1.979 Liters STANDARD_DEVIATION 0.555 • n=7 Participants	1.924 Liters STANDARD_DEVIATION 0.516 • n=5 Participants	1.969 Liters STANDARD_DEVIATION 0.562 • n=4 Participants
Modified Medical Research Council Dyspnea Questionnaire	2.7 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	2.9 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.8 units on a scale STANDARD_DEVIATION 0.6 • n=4 Participants

PRIMARY outcome

Timeframe: 24 hours following two weeks of dosing.

Population: Total number of subjects in each arm: 76, 80, 78

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=71 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=75 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=72 Participants Arformoterol 15 mcg twice daily/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)	0.104 Liters Interval 0.054 to 0.155	0.080 Liters Interval 0.035 to 0.124	0.221 Liters Interval 0.175 to 0.267

SECONDARY outcome

Timeframe: 0-12 hours following two weeks of dosing

Population: Total number of subjects in each arm: 76, 80, 78

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=71 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=75 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=72 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)	0.118 Liters Interval 0.07 to 0.167	0.130 Liters Interval 0.084 to 0.177	0.242 Liters Interval 0.195 to 0.29

SECONDARY outcome

Timeframe: Following 2 weeks of dosing

Population: Total number of subjects in each arm: 76, 80, 78

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=63 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=67 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=71 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)	0.094 Liters Interval 0.036 to 0.151	0.054 Liters Interval 0.008 to 0.101	0.217 Liters Interval 0.169 to 0.264

SECONDARY outcome

Timeframe: Following 2 weeks of dosing

Population: Total number of subjects in each arm: 76, 80, 78

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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=69 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=73 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=74 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)	0.086 Liters Interval 0.031 to 0.141	0.080 Liters Interval 0.032 to 0.129	0.154 Liters Interval 0.103 to 0.206

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/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	0.123 Liters Standard Deviation 0.211	0.143 Liters Standard Deviation 0.226	0.266 Liters Standard Deviation 0.208
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	0.101 Liters Standard Deviation 0.204	0.189 Liters Standard Deviation 0.210
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	0.040 Liters Standard Deviation 0.215	0.235 Liters Standard Deviation 0.202
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	0.063 Liters Standard Deviation 0.213	0.270 Liters Standard Deviation 0.214
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	0.061 Liters Standard Deviation 0.196	0.272 Liters Standard Deviation 0.220
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	0.048 Liters Standard Deviation 0.239	0.240 Liters Standard Deviation 0.216
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	-0.006 Liters Standard Deviation 0.212	0.145 Liters Standard Deviation 0.208
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	0.080 Liters Standard Deviation 0.207	0.154 Liters Standard Deviation 0.223
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	-0.20 Liters Standard Deviation 0.084	0.139 Liters Standard Deviation 0.151
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	0.056 Liters Standard Deviation 0.093	0.183 Liters Standard Deviation 0.152
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 0.150	0.106 Liters Standard Deviation 0.141	0.189 Liters Standard Deviation 0.161
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	0.140 Liters Standard Deviation 0.148	0.239 Liters Standard Deviation 0.170
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	0.120 Liters Standard Deviation 0.169	0.223 Liters Standard Deviation 0.189
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	0.125 Liters Standard Deviation 0.188	0.214 Liters Standard Deviation 0.184
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	0.109 Liters Standard Deviation 0.208	0.194 Liters Standard Deviation 0.180
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 0.150	0.111 Liters Standard Deviation 0.184	0.190 Liters Standard Deviation 0.176
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	0.094 Liters Standard Deviation 0.196	0.199 Liters Standard Deviation 0.202
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	0.066 Liters Standard Deviation 0.184	0.240 Liters Standard Deviation 0.206
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	0.126 Liters Standard Deviation 0.200	0.280 Liters Standard Deviation 0.216
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	0.163 Liters Standard Deviation 0.251	0.308 Liters Standard Deviation 0.232
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	0.195 Liters Standard Deviation 0.248	0.330 Liters Standard Deviation 0.228
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	0.164 Liters Standard Deviation 0.250	0.279 Liters Standard Deviation 0.239
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	0.138 Liters Standard Deviation 0.233	0.220 Liters Standard Deviation 0.215
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	0.109 Liters Standard Deviation 0.179	0.205 Liters Standard Deviation 0.211
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	0.068 Liters Standard Deviation 0.221	0.292 Liters Standard Deviation 0.234

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/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	6.1 Percent of predicted FEV1 Standard Deviation 4.8	3.5 Percent of predicted FEV1 Standard Deviation 4.6	6.3 Percent of predicted FEV1 Standard Deviation 5.4
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 5.0	4.7 Percent of predicted FEV1 Standard Deviation 5.1	8.1 Percent of predicted FEV1 Standard Deviation 5.7
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	3.5 Percent of predicted FEV1 Standard Deviation 6.5	6.6 Percent of predicted FEV1 Standard Deviation 6.2
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	3.7 Percent of predicted FEV1 Standard Deviation 5.6	6.5 Percent of predicted FEV1 Standard Deviation 5.9
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 6.0	2.9 Percent of predicted FEV1 Standard Deviation 6.1	6.7 Percent of predicted FEV1 Standard Deviation 6.6
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	1.9 Percent of predicted FEV1 Standard Deviation 5.9	8.0 Percent of predicted FEV1 Standard Deviation 6.7
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 7.0	4.0 Percent of predicted FEV1 Standard Deviation 6.3	9.3 Percent of predicted FEV1 Standard Deviation 6.9
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	5.2 Percent of predicted FEV1 Standard Deviation 7.6	10.2 Percent of predicted FEV1 Standard Deviation 7.3
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	4.7 Percent of predicted FEV1 Standard Deviation 6.9	8.8 Percent of predicted FEV1 Standard Deviation 6.6
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 7.0	4.4 Percent of predicted FEV1 Standard Deviation 7.1	7.4 Percent of predicted FEV1 Standard Deviation 6.9
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	3.5 Percent of predicted FEV1 Standard Deviation 5.7	6.8 Percent of predicted FEV1 Standard Deviation 6.8
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	3.4 Percent of predicted FEV1 Standard Deviation 6.3	6.3 Percent of predicted FEV1 Standard Deviation 6.9
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	1.1 Percent of predicted FEV1 Standard Deviation 6.8	7.8 Percent of predicted FEV1 Standard Deviation 6.6
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	2.0 Percent of predicted FEV1 Standard Deviation 6.5	9.0 Percent of predicted FEV1 Standard Deviation 7.0
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	1.8 Percent of predicted FEV1 Standard Deviation 6.0	9.1 Percent of predicted FEV1 Standard Deviation 7.1
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	2.0 Percent of predicted FEV1 Standard Deviation 6.7	9.8 Percent of predicted FEV1 Standard Deviation 7.7
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	1.4 Percent of predicted FEV1 Standard Deviation 7.3	8.0 Percent of predicted FEV1 Standard Deviation 6.9
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 7.0	-0.2 Percent of predicted FEV1 Standard Deviation 6.5	4.8 Percent of predicted FEV1 Standard Deviation 6.7
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	2.6 Percent of predicted FEV1 Standard Deviation 6.6	5.2 Percent of predicted FEV1 Standard Deviation 7.2
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	-0.6 Percent of predicted FEV1 Standard Deviation 2.5	4.7 Percent of predicted FEV1 Standard Deviation 4.9
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	2.0 Percent of predicted FEV1 Standard Deviation 3.2	6.1 Percent of predicted FEV1 Standard Deviation 5.2
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	4.0 Percent of predicted FEV1 Standard Deviation 5.3	7.5 Percent of predicted FEV1 Standard Deviation 6.3
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 5.0	4.1 Percent of predicted FEV1 Standard Deviation 5.9	7.3 Percent of predicted FEV1 Standard Deviation 6.3
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	6.3 Percent of predicted FEV1 Standard Deviation 7.3	11.0 Percent of predicted FEV1 Standard Deviation 7.4
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	5.1 Percent of predicted FEV1 Standard Deviation 7.5	9.2 Percent of predicted FEV1 Standard Deviation 7.6

SECONDARY outcome

Timeframe: 2 weeks

12 hour peak change in FEV1 is defined as maximum of the post dose changes through the nominal 12 hour assessment.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline Week 0; N=76, 79, 78	0.264 Liters Interval 0.231 to 0.296	0.218 Liters Interval 0.179 to 0.257	0.311 Liters Interval 0.272 to 0.35
Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline Week 2; N=71, 75, 74	0.273 Liters Interval 0.223 to 0.324	0.265 Liters Interval 0.212 to 0.319	0.379 Liters Interval 0.328 to 0.43

SECONDARY outcome

Timeframe: 2 weeks

Population: Total number of subjects in each arm: 76, 80, 78.

Analyzed from end of dosing to 12 hours.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=42 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=45 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=48 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks	0.39 Hours Interval 0.02 to 7.03	0.72 Hours Interval 0.02 to 10.07	0.17 Hours Interval 0.03 to 6.8

SECONDARY outcome

Timeframe: 2 weeks

Population: Total number of subjects in each arm: 76, 80, 78.

Analyzed from end of dosing to 12 hours.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=30 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=32 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=34 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks	0.76 Hours Interval 0.02 to 7.9	1.29 Hours Interval 0.03 to 7.25	0.39 Hours Interval 0.08 to 10.88

SECONDARY outcome

Timeframe: 2 weeks

Population: Total number of subjects in each arm: 76, 80, 78

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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=66 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=69 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=70 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing	0.074 Liters Interval 0.0 to 0.147	0.023 Liters Interval -0.047 to 0.094	0.150 Liters Interval 0.065 to 0.235

SECONDARY outcome

Timeframe: 2 Weeks

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/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	0.276 Liters Standard Deviation 0.270	-0.031 Liters Standard Deviation 0.165	0.259 Liters Standard Deviation 0.305
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	0.122 Liters Standard Deviation 0.210	0.323 Liters Standard Deviation 0.347
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	0.197 Liters Standard Deviation 0.283	0.351 Liters Standard Deviation 0.348
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	0.248 Liters Standard Deviation 0.279	0.429 Liters Standard Deviation 0.366
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	0.206 Liters Standard Deviation 0.293	0.392 Liters Standard Deviation 0.375
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	0.195 Liters Standard Deviation 0.327	0.371 Liters Standard Deviation 0.352
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	0.159 Liters Standard Deviation 0.360	0.338 Liters Standard Deviation 0.325
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	0.175 Liters Standard Deviation 0.311	0.346 Liters Standard Deviation 0.357
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	0.146 Liters Standard Deviation 0.325	0.344 Liters Standard Deviation 0.352
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	0.055 Liters Standard Deviation 0.301	0.389 Liters Standard Deviation 0.392
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	0.203 Liters Standard Deviation 0.350	0.461 Liters Standard Deviation 0.425
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	0.224 Liters Standard Deviation 0.408	0.487 Liters Standard Deviation 0.426
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	0.290 Liters Standard Deviation 0.387	0.526 Liters Standard Deviation 0.426
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	0.221 Liters Standard Deviation 0.372	0.461 Liters Standard Deviation 0.441
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	0.209 Liters Standard Deviation 0.356	0.413 Liters Standard Deviation 0.383
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	0.214 Liters Standard Deviation 0.319	0.349 Liters Standard Deviation 0.387
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	0.158 Liters Standard Deviation 0.278	0.323 Liters Standard Deviation 0.379
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 0.340	0.124 Liters Standard Deviation 0.365	0.301 Liters Standard Deviation 0.398
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	0.034 Liters Standard Deviation 0.356	0.360 Liters Standard Deviation 0.385
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	0.087 Liters Standard Deviation 0.359	0.399 Liters Standard Deviation 0.407
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	0.082 Liters Standard Deviation 0.329	0.424 Liters Standard Deviation 0.432
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	0.110 Liters Standard Deviation 0.342	0.459 Liters Standard Deviation 0.445
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	0.098 Liters Standard Deviation 0.361	0.374 Liters Standard Deviation 0.422
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	-0.011 Liters Standard Deviation 0.340	0.226 Liters Standard Deviation 0.345
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	0.115 Liters Standard Deviation 0.335	0.250 Liters Standard Deviation 0.408

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once 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 Interval 1.57 to 2.75	1.94 Days per week Interval 1.4 to 2.47	1.38 Days per week Interval 0.87 to 1.89
Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week Baseline: Number of days used per week	4.44 Days per week Interval 3.79 to 5.08	4.27 Days per week Interval 3.61 to 4.92	4.57 Days per week Interval 3.94 to 5.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=76 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=80 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=78 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day Overall: Number of actuations per day	1.18 Actuations per day Interval 0.75 to 1.61	1.00 Actuations per day Interval 0.59 to 1.4	0.68 Actuations per day Interval 0.36 to 1.0
Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day Baseline: Number of actuations per day	3.24 Actuations per day Interval 2.5 to 3.98	2.77 Actuations per day Interval 2.16 to 3.39	3.08 Actuations per day Interval 2.47 to 3.69

SECONDARY outcome

Timeframe: 2 weeks

Population: Total number of subjects in each arm: 76, 80, 78

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.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=75 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=77 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=77 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Transition Dyspnea Index (TDI) Focal Score	2.28 Units on a scale Standard Deviation 2.39	1.79 Units on a scale Standard Deviation 2.83	3.13 Units on a scale Standard Deviation 2.44

SECONDARY outcome

Timeframe: 2 weeks

Population: Total number of subjects in each arm: 76, 80, 78

A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=75 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=77 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=77 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score	50 Participants	44 Participants	60 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: Total number of subjects in each arm: 76, 80, 78

A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important.

Outcome measures

Measure	Arformoterol 15 Mcg Twice Daily n=75 Participants Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily n=77 Participants Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium n=77 Participants Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score	66.67 Percentage of participants	57.14 Percentage of participants	77.92 Percentage of participants

Adverse Events

Arformoterol 15 Mcg Twice Daily

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Tiotropium 18 Mcg Once Daily

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Arformoterol /Tiotropium

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arformoterol 15 Mcg Twice Daily Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Gastrointestinal disorders Small Intestinal Obstruction	1.3% 1/76 • Number of events 1	0.00% 0/80	0.00% 0/78

Other adverse events

Measure	Arformoterol 15 Mcg Twice Daily Arformoterol 15 mcg twice daily/Placebo Inhalation Powder	Tiotropium 18 Mcg Once Daily Tiotropium 18 mcg once daily/Placebo Inhalation Solution	Arformoterol /Tiotropium Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Gastrointestinal disorders Diarrhoea	0.00% 0/76	0.00% 0/80	2.6% 2/78 • Number of events 2
Gastrointestinal disorders Nausea	1.3% 1/76 • Number of events 2	2.5% 2/80 • Number of events 2	0.00% 0/78
General disorders Chest Pain	0.00% 0/76	0.00% 0/80	2.6% 2/78 • Number of events 2
Infections and infestations Bronchitis	2.6% 2/76 • Number of events 2	0.00% 0/80	0.00% 0/78
Nervous system disorders Dizziness	1.3% 1/76 • Number of events 1	1.2% 1/80 • Number of events 1	2.6% 2/78 • Number of events 2
Nervous system disorders Headache	1.3% 1/76 • Number of events 2	3.8% 3/80 • Number of events 4	5.1% 4/78 • Number of events 4
Respiratory, thoracic and mediastinal disorders Cough	1.3% 1/76 • Number of events 1	2.5% 2/80 • Number of events 2	2.6% 2/78 • Number of events 2
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/76	2.5% 2/80 • Number of events 2	0.00% 0/78
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal Pain	2.6% 2/76 • Number of events 3	1.2% 1/80 • Number of events 1	2.6% 2/78 • Number of events 2
Vascular disorders Hypertension	0.00% 0/76	2.5% 2/80 • Number of events 2	2.6% 2/78 • Number of events 2

Additional Information

Respiratory Medical Affairs Director

Sepracor Inc

Phone: 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; provided, 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