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CompletedNCT00424528Updated Jun 4, 2012Results posted

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

A Phase 4 interventional study of Arformoterol Tartrate Inhalation Solution and Tiotropium in Chronic Obstructive Pulmonary Disease, Bronchitis and Emphysema, sponsored by Sumitomo Pharma America, Inc.. Completed at 28 sites in United States. Open to participants aged 45 Years and older. Per ClinicalTrials.gov, last updated 2012-06-04.

Sponsored by Sumitomo Pharma America, Inc. (part of Sumitomo Pharma Co., Ltd.) · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
235
Allocation
Randomized
Ages
45 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate and compare the efficacy of arformoterol twice a day and tiotropium once a day (dosed sequentially) versus tiotropium once a day alone in subjects with Chronic Obstructive Pulmonary Disease (COPD).

Read the detailed description

This study is a multicenter, randomized, modified-blind, double-dummy two-week parallel-group efficacy and safety study of arformoterol tartrate inhalation solution twice daily, tiotropium inhalation powder once daily and arformoterol tartrate inhalation solution twice daily and tiotropium inhalation powder once daily (dosed sequentially) in subjects with COPD. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

02

Conditions studied

  • Chronic Obstructive Pulmonary Disease
  • Bronchitis
  • Emphysema

Keywords

  • COPD including chronic bronchitis and emphysema
03

In context

Pulmonary Disease, Chronic Obstructive

4,252 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 707 are open to participants now.

This study's enrollment of 235 is above the median of 70 across 3,008 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

Browse Pulmonary Disease, Chronic Obstructive studies →

Lead sponsor

Sumitomo Pharma America, Inc. is the lead sponsor of 181 studies on the registry; 5 are open to participants now.

Of its 33 completed or terminated interventional studies of FDA-regulated products, 21 (64%) have results posted.

First submitted before Sumitomo Pharma America, Inc. became part of Sumitomo Pharma Co., Ltd..

Browse Sumitomo Pharma America, Inc. studies →All Sumitomo Pharma Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
45 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Male and female subjects must be at least 45 years old at the time of consent.
  • Subjects must have a pre-established primary clinical diagnosis of COPD.
  • Subjects must have a baseline FEV1 of ≤65% of predicted normal value at Visit 1.
  • Subjects must have a FEV1 ≥ 0.70L at Visit 1.

Exclusion criteria

Exclusion Criteria:

  • Subjects who do not have a FEV1/forced vital capacity (FVC) ratio of ≤70% at Visit 1.
  • Subjects who do not have a ³15 pack-year smoking history and a baseline breathlessness severity grade of ³2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visit 1.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
235 participants (actual)

Study arms

  • Active comparator
    Arformoterol 15 mcg twice daily

    Arformoterol 15 mcg twice daily/Placebo Inhalation Powder

    Drug: Arformoterol Tartrate Inhalation Solution · Drug: Placebo

  • Active comparator
    Tiotropium 18 mcg once daily

    Tiotropium 18 mcg once daily/Placebo Inhalation Solution

    Drug: Tiotropium · Drug: Placebo

  • Experimental
    Arformoterol /Tiotropium

    Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily

    Drug: Arformoterol and Tiotropium

Interventions

  • DrugArformoterol Tartrate Inhalation Solution

    Arformoterol tartrate inhalation solution 15 mcg twice daily and placebo inhalation powder once daily.

    Also known as: Brovana®

  • DrugTiotropium

    Placebo inhalation solution twice daily and tiotropium inhalation powder 18 mcg once daily.

    Also known as: Spiriva

  • DrugArformoterol and Tiotropium

    Drug pages: Formoterol · Tiotropium

    Arformoterol tartrate inhalation solution 15 mcg twice daily and Tiotropium inhalation powder 18 mcg once daily.

    Also known as: Brovana, Spiriva

  • DrugPlacebo

    Placebo inhalation solution and placebo inhalation powder

06

What researchers measure

Primary outcomes

  1. Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)

    Time frame: 24 hours following two weeks of dosing.

Secondary outcomes

  1. Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)

    Time frame: 0-12 hours following two weeks of dosing

  2. Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)

    Time frame: Following 2 weeks of dosing

  3. Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)

    Trough FEV1 is defined as the measurement collected approximately 24 hours after the first in-clinic double-blind dose at Week 0. Change is calculated as Week 2 24 hour post first dose FEV1 - Week 0 pre-first dose FEV1.

    Time frame: Following 2 weeks of dosing

  4. Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication

    Baseline is FEV1 measurement collected prior to the first double-blind dose at week 0. Change defined as Week 0 FEV1 - Week 2 pre first dose FEV1.

    Time frame: 2 weeks

  5. Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication

    Baseline is FEV1 collected prior to first double-blind dose at week 0. Change is defined as Week 0 FEV1 percent predicted - Week 2 pre first dose FEV1 percent predicted.

    Time frame: 2 weeks

  6. Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline

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

    Time frame: 2 weeks

  7. Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks

    Analyzed from end of dosing to 12 hours.

    Time frame: 2 weeks

  8. Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks

    Analyzed from end of dosing to 12 hours.

    Time frame: 2 weeks

  9. Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing

    Trough Inspiratory Capacity is defined as the measurement collected approximately 24 hours after the first in clinic double-blind treatment dose at week 0. Change is calculated as Week 2 24 hr post dose IC - Week 0 pre first dose IC.

    Time frame: 2 weeks

  10. Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint

    Time frame: 2 Weeks

  11. Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week

    Overall: Average of the levalbuterol usage in days per week over the 2 week period. Mean number of days/week=number of days levalbuterol used during time period, divided by number of days in the period, multiplied by 7. An actuation is one puff of levalbuterol.

    Time frame: 2 weeks

  12. Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day

    Overall: Average of the usage in number of actuations per day over the 2 week period. An actuation is one puff of levalbuterol. Mean number of actuations/day=number actuations used during time period, divided by number of days in time period.

    Time frame: 2 weeks

  13. Transition Dyspnea Index (TDI) Focal Score

    TDI Focal score (range -9 to 9) is defined as the sum of function impairment, magnitude of task, and magnitude of effort (each on a -3 to 3 scale). A score of -9 is maximum worsening and 9 is maximum improvement.

    Time frame: 2 weeks

  14. Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score

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

    Time frame: 2 weeks

  15. Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score

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

    Time frame: 2 weeks

07

Results

Posted Apr 2, 2009
Limitations and caveats
As of October 24, 2008, Sepracor is unaware of any limitations or caveats associated with this study.

Participant flow

Multicenter (34 sites) study.

Participant flow — Overall Study
MilestoneArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Started768078
Completed717674
Not completed544
Withdrew: Adverse event212
Withdrew: Protocol violation110
Withdrew: Lost to follow-up010
Withdrew: Noncompliance with study requirements212

Outcome measures

PrimaryTime-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)
Time frame:
24 hours following two weeks of dosing.
Reported as:
Mean · Liters
Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)0.104 (0.054 to 0.155)0.080 (0.035 to 0.124)0.221 (0.175 to 0.267)
Statistical analysis
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = <0.001Study baseline FEV1 as covariate and treatment group as fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = <0.001Study Baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Arformoterol 15 Mcg Twice Daily vs Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = <0.001 (Primary analysis:Group 2 vs 3. Key secondary analysis: Group 1 vs 3. Multiple comparisons for the analysis of the primary endpoint were controlled at the 5% level.)Study baseline FEV1 as a covariate and treatment group as fixed effect.
SecondaryTime-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)
Time frame:
0-12 hours following two weeks of dosing
Reported as:
Mean · Liters
Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)0.118 (0.070 to 0.167)0.130 (0.084 to 0.177)0.242 (0.195 to 0.290)
Statistical analysis
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = <0.001Study baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.001Study baseline FEV1 as a covariate and treatment group as a fixed effect.
SecondaryTime Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)
Time frame:
Following 2 weeks of dosing
Reported as:
Mean · Liters
Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)0.094 (0.036 to 0.151)0.054 (0.008 to 0.101)0.217 (0.169 to 0.264)
Statistical analysis
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.001Study baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = <0.001Study baseline FEV1 as a covariate and treatment group as a fixed effect.
SecondaryChange in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)

Trough FEV1 is defined as the measurement collected approximately 24 hours after the first in-clinic double-blind dose at Week 0. Change is calculated as Week 2 24 hour post first dose FEV1 - Week 0 pre-first dose FEV1.

Time frame:
Following 2 weeks of dosing
Reported as:
Mean · Liters
Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)0.086 (0.031 to 0.141)0.080 (0.032 to 0.129)0.154 (0.103 to 0.206)
Statistical analysis
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.073Study baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.050Study baseline FEV1 as a covariate and treatment group as a fixed effect.
SecondaryChange in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication

Baseline is FEV1 measurement collected prior to the first double-blind dose at week 0. Change defined as Week 0 FEV1 - Week 2 pre first dose FEV1.

Time frame:
2 weeks
Reported as:
Mean · Liters
Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Week 0: immediately post first dose; N=76, 78, 780.132 ± 0.155-0.20 ± 0.0840.139 ± 0.151
Week 0: 30 minutes post first dose; N=75, 78, 760.163 ± 0.1370.056 ± 0.0930.183 ± 0.152
Week 0: 1 hour post first dose; N=75, 78, 770.182 ± 0.1500.106 ± 0.1410.189 ± 0.161
Week 0: 2 hours post first dose; N=76, 78, 770.193 ± 0.1560.140 ± 0.1480.239 ± 0.170
Week 0: 4 hours post first dose; N=75, 77, 770.155 ± 0.1690.120 ± 0.1690.223 ± 0.189
Week 0: 6 hours post first dose; N=72, 74, 770.128 ± 0.1560.125 ± 0.1880.214 ± 0.184
Week 0: 8 hours post first dose; N=70, 73, 770.102 ± 0.1830.109 ± 0.2080.194 ± 0.180
Week 0: 10 hours post first dose; N=69, 71, 760.101 ± 0.1500.111 ± 0.1840.190 ± 0.176
Week 0: 12 hours post first dose; N=69, 71, 750.044 ± 0.1810.094 ± 0.1960.199 ± 0.202
Week 2: immediately post first dose; N=71, 75, 740.154 ± 0.2070.066 ± 0.1840.240 ± 0.206
Week 2: 30 minutes post first dose; N=70, 74, 740.188 ± 0.2220.126 ± 0.2000.280 ± 0.216
Week 2: 1 hour post first dose; N=71, 75, 730.185 ± 0.2220.163 ± 0.2510.308 ± 0.232
Week 2: 2 hours post first dose; N=71, 73, 740.213 ± 0.2260.195 ± 0.2480.330 ± 0.228
Week 2: 4 hours post first dose; N=69, 72, 740.154 ± 0.2270.164 ± 0.2500.279 ± 0.239
Week 2: 6 hours post first dose; N=69, 72, 730.123 ± 0.2110.143 ± 0.2260.266 ± 0.208
Week 2: 8 hours post first dose; N=69, 70, 740.067 ± 0.2210.138 ± 0.2330.220 ± 0.215
Week 2: 10 hours post first dose; N=69, 71, 710.054 ± 0.2240.109 ± 0.1790.205 ± 0.211
Week 2: 12 hours post first dose; N=63, 67, 710.035 ± 0.2110.101 ± 0.2040.189 ± 0.210
Week 2: immediately post second dose; N=65, 67, 720.115 ± 0.2230.040 ± 0.2150.235 ± 0.202
Week 2: 12.5 hours post first dose; N=65, 66, 720.143 ± 0.2350.063 ± 0.2130.270 ± 0.214
Week 2: 13 hours post first dose; N=63, 68, 720.159 ± 0.2340.061 ± 0.1960.272 ± 0.220
Week 2: 14 hours post first dose; N=65, 71, 720.182 ± 0.2480.068 ± 0.2210.292 ± 0.234
Week 2: 16 hours post first dose; N=63, 70, 710.114 ± 0.2330.048 ± 0.2390.240 ± 0.216
Week 2: 23 hours post first dose; N=70, 74, 740.040 ± 0.236-0.006 ± 0.2120.145 ± 0.208
Week 2: 24 hours post first dose; N=69, 73, 740.086 ± 0.2290.080 ± 0.2070.154 ± 0.223
SecondaryChange in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication

Baseline is FEV1 collected prior to first double-blind dose at week 0. Change is defined as Week 0 FEV1 percent predicted - Week 2 pre first dose FEV1 percent predicted.

Time frame:
2 weeks
Reported as:
Mean · Percent of predicted FEV1
Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication
Percent of predicted FEV1Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Week 0: Immediately post first dose; N=76, 78, 784.3 ± 4.6-0.6 ± 2.54.7 ± 4.9
Week 0: 30 minutes post first dose; N=75, 78, 765.5 ± 4.42.0 ± 3.26.1 ± 5.2
Week 0: 1 hour post first dose; N-75, 78, 776.1 ± 4.83.5 ± 4.66.3 ± 5.4
Week 0: 2 hours post first dose; N=76, 78, 776.6 ± 5.04.7 ± 5.18.1 ± 5.7
Week 0: 4 hours post first dose; N=75, 77, 775.3 ± 5.54.0 ± 5.37.5 ± 6.3
Week 0: 6 hours post first dose; N=72, 74, 774.4 ± 5.04.1 ± 5.97.3 ± 6.3
Week 0: 8 hours post first dose; N=70, 73, 773.5 ± 5.53.5 ± 6.56.6 ± 6.2
Week 0: 10 hours post first dose; N=69, 71, 763.3 ± 4.63.7 ± 5.66.5 ± 5.9
Week 0: 12 hours post first dose; N=69, 71, 751.6 ± 6.02.9 ± 6.16.7 ± 6.6
Week 2: Immediately post first dose; N=71, 75, 745.1 ± 6.41.9 ± 5.98.0 ± 6.7
Week 2: 30 minutes post first dose; N=70, 74, 746.2 ± 7.04.0 ± 6.39.3 ± 6.9
Week 2: 1 hour post first dose; N=71, 75, 736.2 ± 7.15.2 ± 7.610.2 ± 7.3
Week 2: 2 hours post first dose; N=71, 73, 747.1 ± 7.16.3 ± 7.311.0 ± 7.4
Week 2: 4 hours post first dose; N=69, 72, 745.1 ± 7.45.1 ± 7.59.2 ± 7.6
Week 2: 6 hours post first dose; N=69, 72, 734.0 ± 6.34.7 ± 6.98.8 ± 6.6
Week 2: 8 hours post first dose; N=69, 70, 742.0 ± 7.04.4 ± 7.17.4 ± 6.9
Week 2: 10 hours post first dose; N=69, 71, 711.8 ± 7.23.5 ± 5.76.8 ± 6.8
Week 2: 12 hours post first dose; N=63, 67, 711.3 ± 6.73.4 ± 6.36.3 ± 6.9
Week 2: Immediately post second dose; N=65, 67, 723.8 ± 6.91.1 ± 6.87.8 ± 6.6
Week 2: 12.5 hours post first dose; N=65, 66, 724.9 ± 7.22.0 ± 6.59.0 ± 7.0
Week 2: 13 hours post first dose; N=63, 68, 725.4 ± 7.31.8 ± 6.09.1 ± 7.1
Week 2: 14 hours post first dose; N=65, 71, 726.0 ± 7.62.0 ± 6.79.8 ± 7.7
Week 2: 16 hours post first dose; N=63, 70, 713.9 ± 7.11.4 ± 7.38.0 ± 6.9
Week 2: 23 hours post first dose; N=70, 74, 741.3 ± 7.0-0.2 ± 6.54.8 ± 6.7
Week 2: 24 hours post first dose; N=69, 73, 742.8 ± 6.92.6 ± 6.65.2 ± 7.2
SecondaryPeak Change in FEV1 Over 12 Hours Post Dose From Study Baseline

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

Time frame:
2 weeks
Reported as:
Mean · Liters
Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Week 0; N=76, 79, 780.264 (0.231 to 0.296)0.218 (0.179 to 0.257)0.311 (0.272 to 0.350)
Week 2; N=71, 75, 740.273 (0.223 to 0.324)0.265 (0.212 to 0.319)0.379 (0.328 to 0.430)
Statistical analysis
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.060Week 0 comparisons: Study baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = <0.001Study baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.004Week 2 comparisons: Study baseline FEV1 as a covariate and treatment group as a fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.002Week 2 comparisons: Study baseline FEV1 as a covariate and treatment group as a fixed effect.
SecondaryTime to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks

Analyzed from end of dosing to 12 hours.

Time frame:
2 weeks
Reported as:
Median · Hours
Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks
HoursArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks0.39 (0.02 to 7.03)0.72 (0.02 to 10.07)0.17 (0.03 to 6.80)
SecondaryTime to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks

Analyzed from end of dosing to 12 hours.

Time frame:
2 weeks
Reported as:
Median · Hours
Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks
HoursArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks0.76 (0.02 to 7.90)1.29 (0.03 to 7.25)0.39 (0.08 to 10.88)
SecondaryChange in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing

Trough Inspiratory Capacity is defined as the measurement collected approximately 24 hours after the first in clinic double-blind treatment dose at week 0. Change is calculated as Week 2 24 hr post dose IC - Week 0 pre first dose IC.

Time frame:
2 weeks
Reported as:
Mean · Liters
Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing0.074 (0.00 to 0.147)0.023 (-0.047 to 0.094)0.150 (0.065 to 0.235)
Statistical analysis
  • Arformoterol 15 Mcg Twice Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.206Study baseline Inspiratory Capacity as a covariate and treatment group as a fixed effect.
  • Tiotropium 18 Mcg Once Daily vs Arformoterol /Tiotropium · ANCOVA · p = 0.025Study baseline Inspiratory Capacity as a covariate and treatment group as a fixed effect.
SecondaryChange in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint
Time frame:
2 Weeks
Reported as:
Mean · Liters
Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint
LitersArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Week 0: Immediately post first dose; N=76, 78, 780.276 ± 0.270-0.031 ± 0.1650.259 ± 0.305
Week 0: 30 minutes post first dose; N=75, 78, 760.312 ± 0.2670.122 ± 0.2100.323 ± 0.347
Week 0: 1 hour post first dose; N=75, 78, 770.344 ± 0.2750.197 ± 0.2830.351 ± 0.348
Week 0: 2 hours post first dose; N=76, 78, 770.376 ± 0.3190.248 ± 0.2790.429 ± 0.366
Week 0: 4 hours post first dose; N=75, 77, 770.291 ± 0.3410.206 ± 0.2930.392 ± 0.375
Week 0: 6 hours post first dose; N=72, 74, 770.242 ± 0.3030.195 ± 0.3270.371 ± 0.352
Week 0: 8 hours post first dose; N=70, 73, 770.207 ± 0.3340.159 ± 0.3600.338 ± 0.325
Week 0: 10 hours post first dose; N=69, 71, 760.209 ± 0.2670.175 ± 0.3110.346 ± 0.357
Week 0: 12 hours post first dose; N=69, 71, 750.131 ± 0.2990.146 ± 0.3250.344 ± 0.352
Week 2: Immediately post first dose; N=71, 75, 740.293 ± 0.3680.055 ± 0.3010.389 ± 0.392
Week 2: 30 minutes post first dose; N=70, 74, 740.343 ± 0.3810.203 ± 0.3500.461 ± 0.425
Week 2: 1 hour post first dose; N=71, 75, 730.350 ± 0.3970.224 ± 0.4080.487 ± 0.426
Week 2: 2 hours post first dose; N=71, 73, 740.380 ± 0.3890.290 ± 0.3870.526 ± 0.426
Week 2: 4 hours post first dose; N=69, 72, 740.265 ± 0.3420.221 ± 0.3720.461 ± 0.441
Week 2: 6 hours post first dose; N=69, 72, 730.202 ± 0.3220.209 ± 0.3560.413 ± 0.383
Week 2: 8 hours post first dose; N=69, 70, 740.136 ± 0.3470.214 ± 0.3190.349 ± 0.387
Week 2: 10 hours post first dose; N=69, 71, 710.098 ± 0.3640.158 ± 0.2780.323 ± 0.379
Week 2: 12 hours post first dose; N=63, 67, 710.087 ± 0.3400.124 ± 0.3650.301 ± 0.398
Week 2: Immediately post second dose; N=65, 67, 720.210 ± 0.3970.034 ± 0.3560.360 ± 0.385
Week 2: 12.5 hours post first dose; N=65, 66, 720.262 ± 0.4160.087 ± 0.3590.399 ± 0.407
Week 2: 13 hours post first dose; N=63, 68, 720.307 ± 0.3760.082 ± 0.3290.424 ± 0.432
Week 2: 14 hours post first dose; N=65, 71, 720.343 ± 0.3860.110 ± 0.3420.459 ± 0.445
Week 2: 16 hours post first dose; N=63, 70, 710.215 ± 0.3740.098 ± 0.3610.374 ± 0.422
Week 2: 23 hours post first dose; N=70, 74, 740.082 ± 0.363-0.011 ± 0.3400.226 ± 0.345
Week 2: 24 hours post first dose; N=69, 73, 740.138 ± 0.3650.115 ± 0.3350.250 ± 0.408
SecondaryLevalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week

Overall: Average of the levalbuterol usage in days per week over the 2 week period. Mean number of days/week=number of days levalbuterol used during time period, divided by number of days in the period, multiplied by 7. An actuation is one puff of levalbuterol.

Time frame:
2 weeks
Reported as:
Mean · Days per week
Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week
Days per weekArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Baseline: Number of days used per week4.44 (3.79 to 5.08)4.27 (3.61 to 4.92)4.57 (3.94 to 5.20)
Overall: Number of days used per week2.16 (1.57 to 2.75)1.94 (1.40 to 2.47)1.38 (0.87 to 1.89)
SecondaryLevalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day

Overall: Average of the usage in number of actuations per day over the 2 week period. An actuation is one puff of levalbuterol. Mean number of actuations/day=number actuations used during time period, divided by number of days in time period.

Time frame:
2 weeks
Reported as:
Mean · Actuations per day
Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day
Actuations per dayArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Baseline: Number of actuations per day3.24 (2.50 to 3.98)2.77 (2.16 to 3.39)3.08 (2.47 to 3.69)
Overall: Number of actuations per day1.18 (0.75 to 1.61)1.00 (0.59 to 1.40)0.68 (0.36 to 1.00)
SecondaryTransition Dyspnea Index (TDI) Focal Score

TDI Focal score (range -9 to 9) is defined as the sum of function impairment, magnitude of task, and magnitude of effort (each on a -3 to 3 scale). A score of -9 is maximum worsening and 9 is maximum improvement.

Time frame:
2 weeks
Reported as:
Mean · Units on a scale
Transition Dyspnea Index (TDI) Focal Score
Units on a scaleArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Transition Dyspnea Index (TDI) Focal Score2.28 ± 2.391.79 ± 2.833.13 ± 2.44
SecondaryNumber of Participants With a >= 1 Unit of Improvement in the TDI Focal Score

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

Time frame:
2 weeks
Reported as:
Number · Participants
Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score
ParticipantsArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score504460
SecondaryPercentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score

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

Time frame:
2 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score
Percentage of participantsArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score66.6757.1477.92

Adverse events

Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arformoterol 15 Mcg Twice Daily———
Tiotropium 18 Mcg Once Daily———
Arformoterol /Tiotropium———
Most frequent serious events
Most frequent serious events
EventArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
Small Intestinal ObstructionGastrointestinal disorders1/760/800/78
Most frequent other events
Most frequent other events
EventArformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /Tiotropium
HeadacheNervous system disorders1/763/804/78
BronchitisInfections and infestations2/760/800/78
Pharyngolaryngeal PainRespiratory, thoracic and mediastinal disorders2/761/802/78
DiarrhoeaGastrointestinal disorders0/760/802/78
Chest PainGeneral disorders0/760/802/78
DizzinessNervous system disorders1/761/802/78
CoughRespiratory, thoracic and mediastinal disorders1/762/802/78
HypertensionVascular disorders0/762/802/78
NauseaGastrointestinal disorders1/762/800/78
Nasal CongestionRespiratory, thoracic and mediastinal disorders0/762/800/78

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
<=18 years0000
Between 18 and 65 years475052149
>=65 years29302685
Age Continuous
Age Continuous(years)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
Mean61.6 ± 8.461.2 ± 9.562.2 ± 7.661.7 ± 8.5
Sex: Female, Male
Sex: Female, Male(Participants)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
Female373736110
Male394342124
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
American Indian or Alaska Native0011
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American56718
White717470215
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
United States768078234
Number of Pack Years Smoked
Number of Pack Years Smoked(Participants)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
>=15 years to <25 years0167
>=25 years to <=30 years44412
>=30 years727568215
Packs per day currently smoked
Packs per day currently smoked(Participants)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
>0 to 1 pack24302276
>1 to 2 packs22241662
>2 to 4 packs3014
>4 packs0000
Currently does not smoke27263992
Baseline Dyspnea Index (BDI) Focal Score
Baseline Dyspnea Index (BDI) Focal Score(units on a scale)Arformoterol 15 Mcg Twice DailyTiotropium 18 Mcg Once DailyArformoterol /TiotropiumTotal
Mean5.8 ± 2.05.8 ± 1.95.5 ± 2.15.7 ± 2.0

5 further baseline measures are reported on the registry.

08

Study locations

28 sites
  • Jasper, Alabama 35501, United States
  • Tucson, Arizona 85715, United States
  • San Diego, California 92120, United States
  • Colorado Springs, Colorado 80909, United States
  • DeFuniak Springs, Florida 32435, United States
  • DeLand, Florida 32720, United States
  • Topeka, Kansas 66606, United States
  • Hazard, Kentucky 41701, United States
  • Madisonville, Kentucky 42431, United States
  • Marrero, Louisiana 70072, United States
  • Sunset, Louisiana 70584, United States
  • Ann Arbor, Michigan 48106, United States
  • Kalamazoo, Michigan 49007, United States
  • Saint Charles, Missouri 63301, United States
  • Charlotte, North Carolina 28207, United States
  • Cincinnati, Ohio 45242, United States
  • Columbus, Ohio 43215, United States
  • Eugene, Oregon 97404, United States
  • Medford, Oregon 97504, United States
  • Portland, Oregon 97213, United States
  • East Providence, Rhode Island 02914, United States
  • Lincoln, Rhode Island 02865, United States
  • Columbia, South Carolina 29201, United States
  • Simpsonville, South Carolina 29681, United States
  • Spartanburg, South Carolina 29303, United States
  • Knoxville, Tennessee 37920, United States
  • Tacoma, Washington 98405, United States
  • Morgantown, West Virginia 26505, United States
09

References and documents

Publications

  • Tashkin DP, Donohue JF, Mahler DA, Huang H, Goodwin E, Schaefer K, Hanrahan JP, Andrews WT. Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD. Respir Med. 2009 Apr;103(4):516-24. doi: 10.1016/j.rmed.2008.12.014. Epub 2009 Feb 8. PubMed 19208459 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 4, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00424528
Lead sponsor
Sumitomo Pharma America, Inc.
Responsible party
Sponsor
First posted
Jan 19, 2007
Start date
Dec 2006
Primary completion
Oct 2007
Completion
Oct 2007
Results posted
Apr 2, 2009
Last update
Jun 4, 2012

Study contacts

William Andrews, M.D.
study director · Sumitomo Pharma America, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Formoterol · Tiotropium

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