Determine the Safety and Efficacy of (R,R)-Formoterol in the Treatment of Subjects With COPD

A Double-Blind, Double-Dummy, Randomized, Placebo- and Active-Controlled, Multicenter, Parallel-Group Study of (R,R)-Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease

The purpose of this study is to assess the bronchodilator effect and safety of multiple daily doses of arformoterol administered for 12 weeks as maintenance treatment in patients with COPD

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Emphysema; Chronic Bronchitis
• Intervention / Treatment: Drug: Placebo; Drug: arformoterol tartrate inhalation solution; Drug: arformoterol tartrate inhalation solution; Drug: arformoterol tartrate inhalation solution; Drug: Salmeterol

Detailed Description

This was a double-blind, double-dummy, randomized, placebo- and active-controlled, multicenter, parallel-group study of adult subjects with COPD. The study was double blinded through the use of both unit dose vial (UDV) and metered-dose inhaler (MDI) placebos, as appropriate. The primary efficacy analysis utilized the placebo control. Secondary analyses of the primary efficacy endpoint utilized the active control, and included comparisons between the placebo and active control. 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): 741
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Jasper, Alabama, United States, 35501
      • Pulmonary & Sleep Associates of Jasper, PC
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, PA
    • Tucson, Arizona, United States, 85712
      • Arizona Clinical Research Center, Inc.
  • California
    • Fair Oaks, California, United States, 95628
      • Northern California Research Corp.
    • Fresno, California, United States, 93720
      • SARC Research Center
    • Fullerton, California, United States, 92835
      • California Research Medical Group, Inc.
    • Irvine, California, United States, 92618
      • Radiant Research-Irvine
    • Newport Beach, California, United States
      • West Coast Clinical Trials
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC
    • Rancho Mirage, California, United States, 92270
      • Advances in Medicine
    • San Diego, California, United States, 92120
      • Institute of HealthCare Assessment, Inc.
    • San Jose, California, United States
      • San Jose Clinical Research
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Medical Group of Diablo Valley, Inc.
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Pulmonary Associates
    • Fort Collins, Colorado, United States
      • Northern Colorado Pulmonary Consultants, PC
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Physicians Research Center, Inc.
  • District of Columbia
    • Washington, District of Columbia, United States
      • Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • DeLand, Florida, United States, 32720
      • University Clinical Research, DeLand
    • Miami Beach, Florida, United States, 33140
      • Mt. Sinai Medical Center
    • Tampa, Florida, United States, 33617
      • Clinical Pharmacology Services
  • Georgia
    • Austell, Georgia, United States, 30106
      • Protocare Trial, Inc.
    • Marietta, Georgia, United States, 30060
      • Marietta Pulmonary Medicine
  • Illinois
    • O'Fallon, Illinois, United States, 62269
      • Office of Bradley Sakran, MD, PC
  • Indiana
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Family Allergy & Asthma Research Institute
    • Somerset, Kentucky, United States
      • Cumberland Lung and Sleep Specialists
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Bendel Medical Associates/Research
    • New Orleans, Louisiana, United States
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70115
      • Best Clinical Trials, LLC
    • Slidell, Louisiana, United States, 70461
      • North Shore Research Associates
    • Sunset, Louisiana, United States, 70584
      • Sunset Medical Research
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland-Airways Research Center
    • Wheaton, Maryland, United States
      • Institute of Asthma and Allergy
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Pro-Medica Clinical Research Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • ClinSite, Inc.
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Medex Healthcare Research, Inc.
    • St. Charles, Missouri, United States, 63301-2847
      • Midwest Chest Consultants, PC
    • St. Louis,, Missouri, United States, 63122
      • C.A.R.E Clinical Research
  • Montana
    • Butte, Montana, United States
      • Office of Keith Popovich, MD
    • Missoula, Montana, United States
      • Montana Medical Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States
      • VA Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Advanced Biomedical Research of America
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Pulmonary Medicine
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Lung and Health Center
    • Statesville, North Carolina, United States, 28625
      • Carolina Pharmaceutical Research, Inc.
    • Wilmington, North Carolina, United States, 28412
      • New Hanover Medical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45241
      • New Horizons Clinical Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • COR Clinical Research LLC
  • Oregon
    • Portland, Oregon, United States, 97213
      • Allergy Associates Research Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Northeast Clinical Research Centers, Inc.
    • Altoona, Pennsylvania, United States, 16602
      • Keystone Clinical Solutions
    • Philadelphia, Pennsylvania, United States, 19146
      • Philadelphia Health Associates - Adult Medicine
    • Ridley Park, Pennsylvania, United States, 19078
      • Consortium Clinical Research, Ltd.
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Safe Harbor Clinical Research
  • South Carolina
    • Spartanburg, South Carolina, United States, 29307
      • Spartanburg Pharmaceutical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
  • Texas
    • Houston, Texas, United States, 77084
      • Breath of Life Research Institute
    • New Braunfels, Texas, United States, 78130
      • Central Texas Health Research
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Pulmonary Associates of Fredericksburg, Inc.
    • Richmond, Virginia, United States, 23225
      • Pulmonary Associates of Richmond, Inc.
  • Washington
    • Bellingham, Washington, United States, 98225
      • Bellingham Asthma, Allergy & Immunology Clinic
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be willing to comply with study procedures and visit schedule
• Are at least 35 years of age
• Female subjects >65 years of age must have a serum pregnancy test conducted at Visit 1 and confirmed negative prior to randomization
• Subjects of childbearing potential must be using an acceptable method of birth control. Female subjects who are considered not of childbearing potential must be: documented surgically sterile, OR postmenopausal.
• Have a primary diagnosis of COPD. Diagnosis can be made during the screening process.
• Have a minimum smoking history of 15 pack-years (pack-years = the number of cigarette packs per day times the number of years).
• Have a chest x-ray that is consistent with the diagnosis of COPD and taken <3 months prior to study start
• Able to complete all study questionnaires and logs reliably

Exclusion Criteria:

• Female subject who is pregnant or lactating
• Have participated in an investigational drug study within 30 days prior to study start, or who is currently participating in another investigational drug study
• Subject whose schedule or travel prevents the completion of all required visits
• Are scheduled for in-patient hospitalization, including elective surgery during the trial
• Have life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days
• History of asthma or any chronic respiratory disease other than COPD (chronic bronchitis and/or emphysema)
• Have clinically significant cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol
• Have a history of cancer except non-melanomatous skin cancer
• Have a history of lung resection of more than one full lobe
• Requires continuous supplemental oxygen therapy.
• Has had a change in dose or type of any medications for COPD within 14 days prior to the screening visit
• Have a known sensitivity to arformoterol, ipratropium, salmeterol or albuterol or any of the excipients contained in any of these formulations
• Have a history of substance abuse or drug abuse within 12 months, or with a positive urine drug screen
• Are using any prescription drug for which concomitant beta-agonist administration is contraindicated (e.g., beta-blockers)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Arformoterol 50 mcg QD and placebo MDI	Drug: arformoterol tartrate inhalation solution; arformoterol 50 mcg QD; Other Names: (R,R)-formoterol; Drug: arformoterol tartrate inhalation solution; arformoterol 25 mcg BID; Other Names: (R,R)-formoterol; Drug: arformoterol tartrate inhalation solution; arformoterol 15 mcg BID; Other Names: Brovana; (R,R)-formoterol
Experimental: 2; Arformoterol 25 mcg BID and Placebo MDI	Drug: arformoterol tartrate inhalation solution; arformoterol 50 mcg QD; Other Names: (R,R)-formoterol; Drug: arformoterol tartrate inhalation solution; arformoterol 25 mcg BID; Other Names: (R,R)-formoterol; Drug: arformoterol tartrate inhalation solution; arformoterol 15 mcg BID; Other Names: Brovana; (R,R)-formoterol
Experimental: 3; Arformoterol 15 mcg BID and placebo MDI	Drug: arformoterol tartrate inhalation solution; arformoterol 50 mcg QD; Other Names: (R,R)-formoterol; Drug: arformoterol tartrate inhalation solution; arformoterol 25 mcg BID; Other Names: (R,R)-formoterol; Drug: arformoterol tartrate inhalation solution; arformoterol 15 mcg BID; Other Names: Brovana; (R,R)-formoterol
Active Comparator: 4; Salmeterol MDI 42 mcg BID and placebo inhalation solution	Drug: Salmeterol; Salmeterol MDI 42 mcg BID; Other Names: Serevent MDI
Placebo Comparator: 5; Placebo MDI and placebo inhalation solution	Drug: Placebo; Placebo BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
percent change in trough FEV1 from study baseline to the end of the dosing interval (12 hours post-second dose for the BID treatment arms and 24 hours postdose for the QD treatment arm) over the double-blind period.	Weeks -2, 0, 3, 6, 9, 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak percent of predicted FEV1	Weeks -2, 0, 3, 6, 9, 12
time-normalized area under the percent change from visit predose curve for FEV1 over 12 hours (nAUC0-12-P)	Weeks -2, 0, 3, 6, 9, 12
time-normalized area under the percent change in FEV1 from study baseline over 12 hours (nAUC0-12-B)	Weeks -2, 0, 3, 6, 9, 12
time-normalized area under the percent change from visit predose curve for FEV1 over 24 hours (nAUC0-24-P)	Weeks -2, 0, 3, 6, 9, 12
time-normalized area under the percent change in FEV1 from study baseline curve over 24 hours (nAUC0-24-B)	Weeks -2, 0, 3, 6, 9, 12
peak percent change in FEV1 from visit predose and study baseline	Weeks -2, 0, 3, 6, 9, 12
time point changes in FEV1; time to onset of response	Weeks -2, 0, 3, 6, 9, 12
time to peak change in FEV1	Weeks -2, 0, 3, 6, 9, 12
at-home and in-clinic peak expiratory flow rate (PEFR)	Weeks -2, 0, 3, 6, 9, 12
relationship between the plasma concentration values and selected pharmacodynamic parameters	Weeks -2, 0, 3, 6, 9, 12, 13
Supplemental ipratropium bromide MDI and racemic albuterol MDI use	Weeks 0-13
COPD exacerbations and COPD symptom ratings	Weeks 0-13
St. George's Hospital Respiratory Questionnaire	Weeks 0, 6, 13
Investigator and Subject Global Evaluations	Weeks -2, 12, 13
Baseline and Transitional Dyspnea Index	Weeks -2, 6, 12
distance walked in six minutes	Weeks -2, 3, 9

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): March 1, 2004
• Study Completion (Actual): March 1, 2004

Study Registration Dates

• First Submitted: July 8, 2003
• First Submitted That Met QC Criteria: July 8, 2003
• First Posted (Estimate): July 9, 2003

Study Record Updates

• Last Update Posted (Estimate): February 22, 2012
• Last Update Submitted That Met QC Criteria: February 21, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bronchial Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis; Bronchitis, Chronic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Pharmaceutical Solutions; Salmeterol Xinafoate; Formoterol Fumarate
• Other Study ID Numbers: 091-051