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

Condition(s) targeted: Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; Emphysema

Intervention: arformoterol tartrate inhalation solution (Drug); arformoterol tartrate inhalation solution (Drug); arformoterol tartrate inhalation solution (Drug); Salmeterol (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Sepracor, Inc.

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

Official title: 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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome: 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.

Secondary outcome:

time-normalized area under the percent change from visit predose curve for FEV1 over 12 hours (nAUC0-12-P)

Peak percent of predicted FEV1

time-normalized area under the percent change in FEV1 from study baseline over 12 hours (nAUC0-12-B)

time-normalized area under the percent change from visit predose curve for FEV1 over 24 hours (nAUC0-24-P)

time-normalized area under the percent change in FEV1 from study baseline curve over 24 hours (nAUC0-24-B)

peak percent change in FEV1 from visit predose and study baseline

time point changes in FEV1; time to onset of response

time to peak change in FEV1

at-home and in-clinic peak expiratory flow rate (PEFR)

relationship between the plasma concentration values and selected pharmacodynamic parameters

Supplemental ipratropium bromide MDI and racemic albuterol MDI use

COPD exacerbations and COPD symptom ratings

St. George's Hospital Respiratory Questionnaire

Investigator and Subject Global Evaluations

Baseline and Transitional Dyspnea Index

distance walked in six minutes

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.

Minimum age: 35 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

Pulmonary & Sleep Associates of Jasper, PC, Jasper, Alabama 35501, United States

Arizona Clinical Research Center, Inc., Tucson, Arizona 85712, United States

Pulmonary Associates, PA, Phoenix, Arizona 85006, United States

Institute of Healthcare Assessment, Inc., San Diego, California 92120, United States

Center for Clinical Trials, LLC, Paramount, California 90723, United States

Advances in Medicine, Rancho Mirage, California 92270, United States

Radiant Research-Irvine, Irvine, California 92618, United States

California Research Medical Group, Inc., Fullerton, California 92835, United States

Allergy & Asthma Medical Group of Diablo Valley, Inc., Walnut Creek, California 94598, United States

SARC Research Center, Fresno, California 93720, United States

Northern California Research Corp., Fair Oaks, California 95628, United States

West Coast Clinical Trials, Newport Beach, California, United States

San Jose Clinical Research, San Jose, California, United States

Colorado Pulmonary Associates, Denver, Colorado 80218, United States

Northern Colorado Pulmonary Consultants, PC, Fort Collins, Colorado, United States

Physicians Research Center, Inc., Hartford, Connecticut 06106, United States

Washington Hospital Center, Washington, District of Columbia, United States

Mt. Sinai Medical Center, Miami Beach, Florida 33140, United States

Clinical Pharmacology Services, Tampa, Florida 33617, United States

University Clinical Research, DeLand, DeLand, Florida 32720, United States

Clinical Research of West Florida, Inc., Clearwater, Florida 33765, United States

Marietta Pulmonary Medicine, Marietta, Georgia 30060, United States

Protocare Trial, Inc., Austell, Georgia 30106, United States

Office of Bradley Sakran, MD, PC, O'Fallon, Illinois 62269, United States

South Bend Clinic, South Bend, Indiana 46617, United States

Family Allergy & Asthma Research Institute, Louisville, Kentucky 40215, United States

Cumberland Lung and Sleep Specialists, Somerset, Kentucky, United States

North Shore Research Associates, Slidell, Louisiana 70461, United States

Bendel Medical Associates/Research, Lafayette, Louisiana 70503, United States

Best Clinical Trials, LLC, New Orleans, Louisiana 70115, United States

Sunset Medical Research, Sunset, Louisiana 70584, United States

New Orleans Center for Clinical Research, New Orleans, Louisiana 70119, United States

New Orleans Center for Clinical Research, New Orleans, Louisiana, United States

University of Maryland-Airways Research Center, Baltimore, Maryland, United States

Institute of Asthma and Allergy, Wheaton, Maryland, United States

Pro-Medica Clinical Research Center, Boston, Massachusetts 02135, United States

ClinSite, Inc., Ann Arbor, Michigan 48106, United States

MedEx HealthCare Research, Inc., Saint Louis, Missouri 63108, United States

C.A.R.E Clinical Research, St. Louis,, Missouri 63122, United States

Midwest Chest Consultants, PC, St. Charles, Missouri 63301-2847, United States

Office of Keith Popovich, MD, Butte, Montana, United States

Montana Medical Research, LLC, Missoula, Montana, United States

VA Medical Center, Omaha, Nebraska, United States

Advanced Biomedical Research of America, Las Vegas, Nevada 89119, United States

Carolina Pharmaceutical Research, Inc., Statesville, North Carolina 28625, United States

Pulmonary Medicine, Chapel Hill, North Carolina 27599, United States

New Hanover Medical Research, Wilmington, North Carolina 28412, United States

Charlotte Lung and Health Center, Charlotte, North Carolina 28207, United States

New Horizons Clinical Research, Inc., Cincinnati, Ohio 45241, United States

COR Clinical Research LLC, Oklahoma City, Oklahoma 73103, United States

Allergy Associates Research Center, Portland, Oregon 97213, United States

Northeast Clinical Research Centers, Inc., Allentown, Pennsylvania 18104, United States

Keystone Clinical Solutions, Altoona, Pennsylvania 16602, United States

Philadelphia Health Associates - Adult Medicine, Philadelphia, Pennsylvania 19146, United States

Consortium Clinical Research, Ltd., Ridley Park, Pennsylvania 19078, United States

Safe Harbor Clinical Research, East Providence, Rhode Island 02914, United States

Spartanburg Pharmaceutical Research, Spartanburg, South Carolina 29307, United States

Volunteer Research Group, Knoxville, Tennessee 37920, United States

Breath of Life Research Institute, Houston, Texas 77084, United States

Central Texas Health Research, New Braunfels, Texas 78130, United States

Sylvana Research Associates, San Antonio, Texas 78229, United States

Pulmonary Associates of Richmond, Inc., Richmond, Virginia 23225, United States

Pulmonary Associates of Fredericksburg, Inc., Fredericksburg, Virginia 22401, United States

Bellingham Asthma, Allergy & Immunology Clinic, Bellingham, Washington 98225, United States

University of Wisconsin-Medical School, Madison, Wisconsin 53792, United States

Starting date: April 2002
Ending date: March 2004
Last updated: June 6, 2008