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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT00424528
First received: January 17, 2007
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

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).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Bronchitis
Emphysema
Drug: Arformoterol Tartrate Inhalation Solution
Drug: Tiotropium
Drug: Arformoterol and Tiotropium
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sunovion:

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) [ Time Frame: 24 hours following two weeks of dosing. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough) [ Time Frame: Following 2 weeks of dosing ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 Weeks ] [ Designated as safety issue: No ]
  • Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important.


Enrollment: 235
Study Start Date: December 2006
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arformoterol 15 mcg twice daily
Arformoterol 15 mcg twice daily/Placebo Inhalation Powder
Drug: Arformoterol Tartrate Inhalation Solution
Arformoterol tartrate inhalation solution 15 mcg twice daily and placebo inhalation powder once daily.
Other Name: Brovana®
Drug: Placebo
Placebo inhalation solution and placebo inhalation powder
Active Comparator: Tiotropium 18 mcg once daily
Tiotropium 18 mcg once daily/Placebo Inhalation Solution
Drug: Tiotropium
Placebo inhalation solution twice daily and tiotropium inhalation powder 18 mcg once daily.
Other Name: Spiriva
Drug: Placebo
Placebo inhalation solution and placebo inhalation powder
Experimental: Arformoterol /Tiotropium
Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Drug: Arformoterol and Tiotropium
Arformoterol tartrate inhalation solution 15 mcg twice daily and Tiotropium inhalation powder 18 mcg once daily.
Other Names:
  • Brovana
  • Spiriva

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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424528

  Hide Study Locations
Locations
United States, Alabama
Jasper, Alabama, United States, 35501
United States, Arizona
Tucson, Arizona, United States, 85715
United States, California
San Diego, California, United States, 92120
United States, Colorado
Colorado Springs, Colorado, United States, 80909
United States, Florida
DeFuniak Springs, Florida, United States, 32435
DeLand, Florida, United States, 32720
United States, Kansas
Topeka, Kansas, United States, 66606
United States, Kentucky
Hazard, Kentucky, United States, 41701
Madisonville, Kentucky, United States, 42431
United States, Louisiana
Marrero, Louisiana, United States, 70072
Sunset, Louisiana, United States, 70584
United States, Michigan
Ann Arbor, Michigan, United States, 48106
Kalamazoo, Michigan, United States, 49007
United States, Missouri
St. Charles, Missouri, United States, 63301
United States, North Carolina
Charlotte, North Carolina, United States, 28207
United States, Ohio
Cincinnati, Ohio, United States, 45242
Columbus, Ohio, United States, 43215
United States, Oregon
Eugene, Oregon, United States, 97404
Medford, Oregon, United States, 97504
Portland, Oregon, United States, 97213
United States, Rhode Island
E. Providence, Rhode Island, United States, 02914
Lincoln, Rhode Island, United States, 02865
United States, South Carolina
Columbia, South Carolina, United States, 29201
Simpsonville, South Carolina, United States, 29681
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Knoxville, Tennessee, United States, 37920
United States, Washington
Tacoma, Washington, United States, 98405
United States, West Virginia
Morgantown, West Virginia, United States, 26505
Sponsors and Collaborators
Sunovion
Investigators
Study Director: William Andrews, M.D. Sunovion
  More Information

Additional Information:
No publications provided by Sunovion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT00424528     History of Changes
Other Study ID Numbers: 091-902
Study First Received: January 17, 2007
Results First Received: October 24, 2008
Last Updated: May 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sunovion:
COPD including chronic bronchitis and emphysema

Additional relevant MeSH terms:
Bronchitis
Emphysema
Pulmonary Emphysema
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Pathologic Processes
Formoterol
Tiotropium
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on July 29, 2014