Safety Study of Arformoterol Tartrate Inhalation Solution in Chronic Obstructive Pulmonary Disease (COPD) Subjects
- Conditions
- Chronic Obstructive Pulmonary Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT00909779
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This is a multi-center study to evaluate the long-term safety of arformoterol 15 mcg twice daily (BID) in the treatment of subjects with moderate-to-severe COPD. Study participation will consist of a total of 6 visits over approximately 1 year.
- Detailed Description
This is a multi-center, double-blind, randomized, placebo-controlled, parallel-group, outpatient, safety study to evaluate the long-term safety of arformoterol 15 mcg twice daily (BID) in the treatment of subjects with moderate-to-severe COPD. The administration of arformoterol in subjects with moderate to severe COPD will not result in a meaningfully greater incidence of respiratory death and COPD exacerbation -related hospitalizations compared to placebo (nebulized saline and non-long-acting beta2-agonist \[LABA\] COPD standard of care treatments). 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 841
- Subject must give written informed consent, including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation.
- Females considered not of childbearing potential must be surgically sterile (total hysterectomy, bilateral salpingo oophorectomy, or tubal ligation) or post-menopausal, which is defined as a complete cessation of menstruation for at least 1 year.
- Male and female subjects must be at least 40 years old at the time of consent.
- Subjects must have a pre-established, documented primary clinical diagnosis of non-asthmatic COPD or are referred for diagnosis of non-asthmatic COPD.
- Subjects must have a baseline FEV1 of ≤50% predicted volume at Visits 1 and 2 (pre-dose).
- Subjects must have a FEV1 >0.50 L at either Visit 1 or 2 (pre-dose).
- Subject's respiratory status must be clinically stable.
- Subjects must have a FEV1/forced vital capacity (FVC) ratio of ≤70% at either Visit 1 or 2 (pre-dose).
- Subjects must have had at least 1 COPD exacerbation within the last year (defined as initiation or an increase in the dose of oral steroids or antibiotics for the treatment of COPD).
- Subjects must have a ≥15 pack-year smoking history and a baseline breathlessness severity grade of ≥2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visit 2.
- Female subjects ≤65 years of age must have a negative serum pregnancy test conducted at Visit 1 prior to randomization. Females of childbearing potential must be using an acceptable method of birth control.
- Subjects' overall health must be sufficiently stable to complete the study requirements based on the screening physical examination (defined as the absence of any clinically relevant abnormalities), medical history, 12-lead ECG, and clinical laboratory values (hematology, serum chemistry and urinalysis), and vital signs (heart rate, respiratory rate, and blood pressure) that have been conducted within 30 days of Visit 2 (randomization). If any of the hematology, chemistry, or urinalysis results are not within the laboratory's reference range, then the subject can be included only if the investigator judges the deviations to be not clinically significant.
- Subjects must have a minimum blood pressure of 105/60 mmHg and a minimum resting pulse of 50 bpm at Screening Visit 1. Subjects who do not meet these criteria at Screening Visit 1 must meet the criteria on the first day of dosing (Day 1) in order to be eligible for the study. Subjects with a medical condition which causes low blood pressure or low heart rate, but, in the opinion of the Principal Investigator or designee the medical condition could resolve, may be rescreened when the condition is resolved.
- Subjects must be willing and able to complete all study questionnaires and logs reliably.
- Subjects must be willing and able to comply with study procedures and visit schedule.
- Subjects must have sufficient understanding of English to complete all questionnaires and logs.
- Female subjects who are pregnant or lactating.
- Subjects with a history of asthma, with the exception of asthma diagnosed in childhood.
- Subjects with a blood eosinophil count >5% of total white blood cell count.
- Subjects with a febrile illness within 3 days before Screening.
- Subjects with a malignant neoplasm other than non melanomatous basal cell skin cancer. Subjects with a history of malignancy who have been cancer free for 5 years or more may be enrolled.
- Subjects who are currently using disallowed medications or will be unable to complete the medication washout periods. Subjects taking a prohibited concurrent medication which requires a washout of >30 days may be rescreened when the washout of the prohibited concurrent medication has been met.
- Subjects with life threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to screening.
- Subjects who have had a change in dose or type of any medications for COPD within 2 weeks prior to the screening visit. Subjects not on a stable dose of COPD medications may be rescreened after being on a stable dose for at least 14 days
- Subjects with a chest x ray taken ≤3 months prior to screening that suggests a diagnosis other than COPD (eg, diagnostic of pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions). If there is no chest x ray taken ≤3 months prior to screening, or if recent results are unavailable for review, a chest x ray must be performed prior to visit 2. Subjects with a medical condition that caused the abnormal finding, but, in the opinion of the Principal Investigator or designee the medical condition could resolve, may be rescreened when the condition is resolved
- Subjects with a positive urine drug test during screening.
- Subjects with a known history of alcohol abuse may be enrolled in the study if the subject's current alcohol use does not exceed more than 3 alcoholic beverages per day.
- Subjects whose schedule or travel prevents the completion of all required visits.
- Subjects who are scheduled for inpatient hospitalization or elective surgery (inpatient or outpatient) during the trial. Subjects may be rescreened when the condition is resolved.
- Subjects have participated in an investigational drug study and/or any COPD interventional trial within 30 days prior to screening or who are currently participating in another investigational drug study or COPD interventional trial.
- Subjects with a history of allergic reaction to the study medication or any components of the study medications.
- Subjects who are study site staff members or relatives of study site staff members directly involved in this study.
- Subjects with clinically significant cardiac, (Functional Class III and IV; Objective Class C and D by New York Heart Association [NYHA] Functional Classification),hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arformoterol 15 mcg twice daily Arformoterol Arformoterol 15 mcg twice daily by nebulization. All subjects will be dispensed albuterol HFA metered-dose inhaler (MDI) to be used as needed as rescue medication for bronchospasm and acute treatment of COPD symptoms. Placebo twice daily Placebo Placebo twice daily by nebulization. All subjects will be dispensed albuterol HFA metered-dose inhaler (MDI) to be used as needed as rescue medication for bronchospasm and acute treatment of COPD symptoms.
- Primary Outcome Measures
Name Time Method Time From Randomization to Respiratory Death or First COPD Exacerbation Related Hospitalization (Whichever Occurs First). 0-12 months COPD exacerbation: an increase in COPD symptoms that necessitated any change in baseline medication (bronchodilators,anti-inflammatory agents, antibiotics, supplemental oxygen therapy, etc.).Hospitalization: any inpatient admission or any emergency department visit \> 24 hours in duration. Hospice was considered hospitalization.COPD exacerbation related hospitalization: hospitalization that was due to 1) COPD exacerbation or 2) a COPD exacerbation preceded, or occurred concomitantly with the onset of, the event for which the subject was hospitalized.Respiratory-related death: For each death the Primary Investigator designated a 'probable cause', which was the primary condition that precipitated the terminal events that were the immediate cause of death. If a probable cause could not be ascertained, the cause of death was considered 'UNKNOWN'. Cause other than 'UNKNOWN' was categorized as either respiratory or non-respiratory. Deaths of 'UNKNOWN' cause were counted as primary events.
- Secondary Outcome Measures
Name Time Method The Incidence of Treatment Emergent AEs 0-12 months TEAEs were defined as: 1) adverse events that occurred on or after the date of first dose of study medication, 2) adverse events with a missing start date and a stop date on or after the date of first does of study medication, or 3) adverse events with both a missing start and stop date.
The frequency and percentage of subjects with TEAEs were summarized. At each level of summarization, a subject was counted only once for each AE he/she experienced within that level. The percentage of subjects having had at least 1 AE at each level was calculated.SGRQ: Mean Change From Baseline in Total Score Baseline and on treatment at months 3, 6 and 12 (or early termination) The SGRQ assessed health status and consisted of 3 component scores (Symptoms, Activity, and Impacts) as well as a total score. Items were scored in accordance with the developer's guidelines. Scores were expressed as a percentage of overall impairment, where 100 represented worst possible health status and 0 indicated best possible health status. The SGRQ was assessed pre-dose at baseline, months 3, 6 and 12 or the end of study (EOS). Visit 2 was defined as baseline. A change from baseline in the Total Score of ≥ 4 units is considered the minimal clinically important difference (MCID) for SGRQ.
Forced Vital Capacity (FVC): Mean Change From Baseline Baseline and on treatment at months 3, 6, 9 and 12 (or early termination) Forced Vital capacity: the volume of air that can forcibly be blown out after full inspiration. Best FVC was measured at Visit 1 (screening), pre-dose at baseline, months 3, 6, 9 and 12/EOS. The best FVC from at least 3 acceptable maneuvers was recorded.
The Incidence of Protocol Defined COPD Exacerbations. 0-12 months A protocol-defined exacerbation of COPD was defined as an increase in respiratory symptoms (classically, increased shortness of breath, increased sputum production, and/or increased sputum purulence) that necessitates any change in baseline medication other than bronchodilators (e.g., anti-inflammatory agents, antibiotics, supplemental oxygen therapy, etc) or causes the subject to require additional medical attention (i.e., emergency room visit or hospitalization).
The Incidence of All Cause Mortality 0-12 months Survival status at the end of the study will be determined for each subject. The proportion of subjects dead and the annual event rate will be summarized by treatment.
FEV1: Mean Change From Baseline Baseline and on treatments at months 3, 6, 9 and 12 (or early termination) FEV1 was measured at Visit 1 (screening), pre- and post-albuterol administration for reversibility testing, pre-dose at baseline, months 3, 6, 9 and 12/EOS. The best FEV1 from at least 3 acceptable maneuvers was recorded. Study baseline was defined as the Visit 2 pre-dose value. If the Visit 2 pre-dose value was missing, the last FEV1 value obtained prior to first treatment was used for baseline.
Percent Predicted FEV1: Mean Change From Baseline Baseline and on treatments at months 3, 6, 9 and 12 (or early termination) Percent predicted FEV1: measured FEV1 as a percent of the "predicted values" for the patients of similar characteristics (height, age, sex, and sometimes race and weight). Best FEV1 percent predicted was measured at Visit 1 (screening), pre-dose at baseline, months 3, 6, 9 and 12/EOS, as described for FEV1.
Inspiratory Capacity (IC): Mean Change From Baseline Baseline and on treatment at months 3, 6, 9 and 12 (or early termination) IC: the total amount of air that can be drawn into the lungs after normal expiration.
IC was measured pre- and post-albuterol administration at Visit 1 (screening), pre-dose at baseline, months 3, 6, 9 and 12/EOS. IC maneuvers were done in triplicate. The mean of all recorded IC values was used for each subject at each time point. Study baseline was defined as the Visit 2 pre-dose value. If the Visit 2 pre-dose value was missing, the last IC value obtained prior to first treatment dose was used for baseline.
Trial Locations
- Locations (69)
C.A.R.E. Clinical Research
🇺🇸St. Louis, Missouri, United States
Neem Research Group, Inc.
🇺🇸Columbia, South Carolina, United States
DCT
🇺🇸Sugar Land, Texas, United States
S. Carolina Pharmaceutical Research
🇺🇸Spartanburg, South Carolina, United States
Arcuri Clinical Research, LLC
🇺🇸Philadelphia, Pennsylvania, United States
VAMC
🇺🇸Houston, Texas, United States
Institute of HealthCare Assessment, Inc.
🇺🇸San Diego, California, United States
Bernstein Clinical Research Center
🇺🇸Cincinnati, Ohio, United States
Chest Critical Care Consultants
🇺🇸Anaheim, California, United States
California Research Medical Group
🇺🇸Fullerton, California, United States
Tampa Bay Medical Research Inc.
🇺🇸Clearwater, Florida, United States
Centers for Clinical Trials of Sacremento
🇺🇸Sacremento, California, United States
Southeast Clinical Research
🇺🇸Chiefland, Florida, United States
Quality Control Research Inc.
🇺🇸Roseville, California, United States
The Lung Clinic, P.A.
🇺🇸Kissimmee, Florida, United States
Rochester Clinical Research
🇺🇸Rochester, New York, United States
Jasper Summit Research, LLC
🇺🇸Jasper, Alabama, United States
Omega Medical Research
🇺🇸Warwick, Rhode Island, United States
AAIR Research Center
🇺🇸Rochester, New York, United States
Midwest Chest Consultants
🇺🇸St. Charles, Missouri, United States
Greenville Pharmaceutical Research
🇺🇸Greenville, South Carolina, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Clinical Research of West Florida, Inc.
🇺🇸Clearwater, Florida, United States
Integrated Research Group
🇺🇸Riverside, California, United States
Atlanta Pharmaceutical Research
🇺🇸Decatur, Georgia, United States
Southeast Regional Research Group
🇺🇸Rincon, Georgia, United States
Bendel Medical Research Center, LLC
🇺🇸Lafayette, Louisiana, United States
Volunteer Research Group
🇺🇸Knoxville, Tennessee, United States
Biomedical Research Alliance at Hypertension and Nephrology
🇺🇸Pawtucket, Rhode Island, United States
Gaffney Pharmaceutical Research
🇺🇸Gaffney, South Carolina, United States
Clinical Research Institute of Southern Oregon, PC
🇺🇸Medford, Oregon, United States
Baylor College of Medicine, Clinical Studies Unit, Ben Taub General Hospital
🇺🇸Houston, Texas, United States
Medisphere Medical Research Center
🇺🇸Evansville, Indiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Pulmonary Consultants, PLLC
🇺🇸Tacoma, Washington, United States
Wellstar Marietta Pulmonary Medicine
🇺🇸Marietta, Georgia, United States
Comprehensive Clinical Research
🇺🇸Berlin, New Jersey, United States
American Health Research Inc.
🇺🇸Charlotte, North Carolina, United States
ENT & Allergy Associates
🇺🇸Newburgh, New York, United States
Mountain View Clinical Research, Inc.
🇺🇸Greer, South Carolina, United States
CU Pharmaceutical Research
🇺🇸Union, South Carolina, United States
National Clinical Resources, Inc.
🇺🇸Provo, Utah, United States
Charlottesville Medical Research Inc.
🇺🇸Charlottesville, Virginia, United States
Physician PrimeCare Research
🇺🇸San Antonio, Texas, United States
Clinical Research Institute Inc.
🇺🇸Minneapolis, Minnesota, United States
Diagnostics Research Group
🇺🇸San Antonio, Texas, United States
Jefferson Clinic
🇺🇸Birmingham, Alabama, United States
Alabama Clinical Therapeutic, LLC
🇺🇸Birmingham, Alabama, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Allergy Associates Research Center
🇺🇸Portland, Oregon, United States
Utah Clinical Trials LLC
🇺🇸Salt Lake City, Utah, United States
Clinical Research of West Florida
🇺🇸Tampa, Florida, United States
Sockolov and Sockolov APC
🇺🇸Sacramento, California, United States
ClinSite LLC
🇺🇸Ann Arbor, Michigan, United States
Piedmont Medical Research
🇺🇸Winston-Salem, North Carolina, United States
Achieve Clinical Research
🇺🇸Brimingham, Alabama, United States
Avail Clinical Research
🇺🇸DeLand, Florida, United States
Kentucky Lung Clinic
🇺🇸Hazard, Kentucky, United States
DayStar Clinical Research, Inc.
🇺🇸Akron, Ohio, United States
Delaware Valley Clinical Research
🇺🇸Cherry Hill, New Jersey, United States
New York Pulmonary and Clinical Care Associates, PC
🇺🇸New York, New York, United States
Allergy Associates
🇺🇸Knoxville, Tennessee, United States
Upstate Pharmaceutical Research
🇺🇸Greenville, South Carolina, United States
Kingwood Research Institute, LLC
🇺🇸Kingwood, Texas, United States
SouthEast Research Institute
🇺🇸Webster, Texas, United States
Lowcountry Lung & Critical Care, PA
🇺🇸Charleston, South Carolina, United States
Pulmonary Associates of Richmond Inc.
🇺🇸Richmond, Virginia, United States
Dominion Medical Associates
🇺🇸Richmond, Virginia, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸Richmond, Virginia, United States