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

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Emphysema; Bronchitis
• Intervention / Treatment: Drug: Arformoterol Tartrate Inhalation Solution; Drug: Placebo; Drug: Tiotropium; Drug: Arformoterol and Tiotropium

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.

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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: Placebo; Placebo inhalation solution and placebo inhalation powder; Drug: Tiotropium; Placebo inhalation solution twice daily and tiotropium inhalation powder 18 mcg once daily.; Other Names: Spiriva
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: Spiriva; Brovana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)	24 hours following two weeks of dosing.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)		0-12 hours following two weeks of dosing
Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)		Following 2 weeks of dosing
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.	Following 2 weeks of dosing
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.	2 weeks
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.	2 weeks
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.	2 weeks
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.	2 weeks
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.	2 weeks
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.	2 weeks
Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint		2 Weeks
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.	2 weeks
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.	2 weeks
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.	2 weeks
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.	2 weeks
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.	2 weeks

Collaborators and Investigators

• Sponsor: Sunovion
• Investigators: Study Director: William Andrews, M.D., Sunovion

Publications and helpful links

General 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.

Helpful Links

• Brovana® Patient Medication Guide

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 18, 2007
• First Posted (Estimate): January 19, 2007

Study Record Updates

• Last Update Posted (Estimate): June 4, 2012
• Last Update Submitted That Met QC Criteria: May 29, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: COPD including chronic bronchitis and emphysema
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bronchial Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema; Bronchitis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tiotropium Bromide; Formoterol Fumarate
• Other Study ID Numbers: 091-902