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

Primary Purpose

Chronic Obstructive Pulmonary Disease, Bronchitis, Emphysema

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Arformoterol Tartrate Inhalation Solution
Tiotropium
Arformoterol and Tiotropium
Placebo
Sponsored by
Sumitomo Pharma America, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD including chronic bronchitis and emphysema

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Experimental

Arm Label

Arformoterol 15 mcg twice daily

Tiotropium 18 mcg once daily

Arformoterol /Tiotropium

Arm Description

Arformoterol 15 mcg twice daily/Placebo Inhalation Powder

Tiotropium 18 mcg once daily/Placebo Inhalation Solution

Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)
Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)
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.
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.
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.
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 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 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.
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.
Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint
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.
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.
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.
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.
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.

Full Information

First Posted
January 17, 2007
Last Updated
May 29, 2012
Sponsor
Sumitomo Pharma America, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00424528
Brief Title
Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)
Official Title
A Two-Week, Randomized, Modified-Blind, Double-Dummy, Parallel-Group Efficacy and Safety Study of Arformoterol Tartrate Inhalation Solution Twice-Daily, Tiotropium Once-Daily, and Arformoterol Tartrate Inhalation Solution Twice-Daily and Tiotropium Once Daily in Subjects With Chronic Obstructive Pulmonary Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sumitomo Pharma America, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate and compare the efficacy of arformoterol twice a day and tiotropium once a day (dosed sequentially) versus tiotropium once a day alone in subjects with Chronic Obstructive Pulmonary Disease (COPD).
Detailed Description
This study is a multicenter, randomized, modified-blind, double-dummy two-week parallel-group efficacy and safety study of arformoterol tartrate inhalation solution twice daily, tiotropium inhalation powder once daily and arformoterol tartrate inhalation solution twice daily and tiotropium inhalation powder once daily (dosed sequentially) in subjects with COPD. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease, Bronchitis, Emphysema
Keywords
COPD including chronic bronchitis and emphysema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
235 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arformoterol 15 mcg twice daily
Arm Type
Active Comparator
Arm Description
Arformoterol 15 mcg twice daily/Placebo Inhalation Powder
Arm Title
Tiotropium 18 mcg once daily
Arm Type
Active Comparator
Arm Description
Tiotropium 18 mcg once daily/Placebo Inhalation Solution
Arm Title
Arformoterol /Tiotropium
Arm Type
Experimental
Arm Description
Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Intervention Type
Drug
Intervention Name(s)
Arformoterol Tartrate Inhalation Solution
Other Intervention Name(s)
Brovana®
Intervention Description
Arformoterol tartrate inhalation solution 15 mcg twice daily and placebo inhalation powder once daily.
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Other Intervention Name(s)
Spiriva
Intervention Description
Placebo inhalation solution twice daily and tiotropium inhalation powder 18 mcg once daily.
Intervention Type
Drug
Intervention Name(s)
Arformoterol and Tiotropium
Other Intervention Name(s)
Brovana, Spiriva
Intervention Description
Arformoterol tartrate inhalation solution 15 mcg twice daily and Tiotropium inhalation powder 18 mcg once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo inhalation solution and placebo inhalation powder
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
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
Title
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
Title
Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)
Description
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
Title
Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication
Description
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
Title
Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication
Description
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
Title
Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline
Description
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
Title
Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks
Description
Analyzed from end of dosing to 12 hours.
Time Frame
2 weeks
Title
Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks
Description
Analyzed from end of dosing to 12 hours.
Time Frame
2 weeks
Title
Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing
Description
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
Title
Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint
Time Frame
2 Weeks
Title
Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week
Description
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
Title
Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day
Description
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
Title
Transition Dyspnea Index (TDI) Focal Score
Description
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
Title
Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score
Description
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
Title
Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female subjects must be at least 45 years old at the time of consent. Subjects must have a pre-established primary clinical diagnosis of COPD. Subjects must have a baseline FEV1 of ≤65% of predicted normal value at Visit 1. Subjects must have a FEV1 ≥ 0.70L at Visit 1. Exclusion Criteria: Subjects who do not have a FEV1/forced vital capacity (FVC) ratio of ≤70% at Visit 1. Subjects who do not have a ³15 pack-year smoking history and a baseline breathlessness severity grade of ³2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visit 1.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Andrews, M.D.
Organizational Affiliation
Sumitomo Pharma America, Inc.
Official's Role
Study Director
Facility Information:
City
Jasper
State/Province
Alabama
ZIP/Postal Code
35501
Country
United States
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
City
DeFuniak Springs
State/Province
Florida
ZIP/Postal Code
32435
Country
United States
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606
Country
United States
City
Hazard
State/Province
Kentucky
ZIP/Postal Code
41701
Country
United States
City
Madisonville
State/Province
Kentucky
ZIP/Postal Code
42431
Country
United States
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
City
Sunset
State/Province
Louisiana
ZIP/Postal Code
70584
Country
United States
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
City
St. Charles
State/Province
Missouri
ZIP/Postal Code
63301
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97404
Country
United States
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
City
E. Providence
State/Province
Rhode Island
ZIP/Postal Code
02914
Country
United States
City
Lincoln
State/Province
Rhode Island
ZIP/Postal Code
02865
Country
United States
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29201
Country
United States
City
Simpsonville
State/Province
South Carolina
ZIP/Postal Code
29681
Country
United States
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26505
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19208459
Citation
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.
Results Reference
derived

Learn more about this trial

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

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