Safety Study of Arformoterol Tartrate Inhalation Solution in Chronic Obstructive Pulmonary Disease (COPD) Subjects

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Large Simple Safety Study of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00909779
• Other study ID #: 091-080
• Status: Completed
• Phase: Phase 3
• First received: May 26, 2009
• Last updated: September 12, 2013
• Start date: June 2009
• Est. completion date: June 2012

Study information

• Verified date: September 2013
• Source: Sunovion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 841
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Arformoterol
Arformoterol Tartrate Inhalation Solution 15 mcg twice daily (BID) for a duration of one year
• Placebo
Placebo inhalation solution, twice daily (BID) for a duration of one year.

Locations

Country	Name	City	State
United States	DayStar Clinical Research, Inc.	Akron	Ohio
United States	Chest Critical Care Consultants	Anaheim	California
United States	ClinSite LLC	Ann Arbor	Michigan
United States	DCT	Arlington	Texas
United States	Comprehensive Clinical Research	Berlin	New Jersey
United States	Alabama Clinical Therapeutic, LLC	Birmingham	Alabama
United States	Jefferson Clinic	Birmingham	Alabama
United States	Achieve Clinical Research	Brimingham	Alabama
United States	Lowcountry Lung & Critical Care, PA	Charleston	South Carolina
United States	American Health Research Inc.	Charlotte	North Carolina
United States	Charlottesville Medical Research Inc.	Charlottesville	Virginia
United States	Delaware Valley Clinical Research	Cherry Hill	New Jersey
United States	Southeast Clinical Research	Chiefland	Florida
United States	Bernstein Clinical Research Center	Cincinnati	Ohio
United States	Clinical Research of West Florida, Inc.	Clearwater	Florida
United States	Tampa Bay Medical Research Inc.	Clearwater	Florida
United States	Neem Research Group, Inc.	Columbia	South Carolina
United States	Southeast Regional Research Group	Columbus	Georgia
United States	Atlanta Pharmaceutical Research	Decatur	Georgia
United States	Avail Clinical Research	DeLand	Florida
United States	National Jewish Health	Denver	Colorado
United States	Medisphere Medical Research Center	Evansville	Indiana
United States	California Research Medical Group	Fullerton	California
United States	Gaffney Pharmaceutical Research	Gaffney	South Carolina
United States	Greenville Pharmaceutical Research	Greenville	South Carolina
United States	Upstate Pharmaceutical Research	Greenville	South Carolina
United States	Mountain View Clinical Research, Inc.	Greer	South Carolina
United States	Kentucky Lung Clinic	Hazard	Kentucky
United States	Baylor College of Medicine, Clinical Studies Unit, Ben Taub General Hospital	Houston	Texas
United States	VAMC	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Jasper Summit Research, LLC	Jasper	Alabama
United States	Kingwood Research Institute, LLC	Kingwood	Texas
United States	The Lung Clinic, P.A.	Kissimmee	Florida
United States	Allergy Associates	Knoxville	Tennessee
United States	Volunteer Research Group	Knoxville	Tennessee
United States	Bendel Medical Research Center, LLC	Lafayette	Louisiana
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Wellstar Marietta Pulmonary Medicine	Marietta	Georgia
United States	Clinical Research Institute of Southern Oregon, PC	Medford	Oregon
United States	Clinical Research Institute Inc.	Minneapolis	Minnesota
United States	New York Pulmonary and Clinical Care Associates, PC	New York	New York
United States	ENT & Allergy Associates	Newburgh	New York
United States	DCT	Orlando	Florida
United States	Biomedical Research Alliance at Hypertension and Nephrology	Pawtucket	Rhode Island
United States	Arcuri Clinical Research, LLC	Philadelphia	Pennsylvania
United States	Allergy Associates Research Center	Portland	Oregon
United States	National Clinical Resources, Inc.	Provo	Utah
United States	Dominion Medical Associates	Richmond	Virginia
United States	Pulmonary Associates of Richmond Inc.	Richmond	Virginia
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	Southeast Regional Research Group	Rincon	Georgia
United States	Integrated Research Group	Riverside	California
United States	AAIR Research Center	Rochester	New York
United States	Rochester Clinical Research	Rochester	New York
United States	Quality Control Research Inc.	Roseville	California
United States	Sockolov and Sockolov APC	Sacramento	California
United States	Centers for Clinical Trials of Sacremento	Sacremento	California
United States	Utah Clinical Trials LLC	Salt Lake City	Utah
United States	Diagnostics Research Group	San Antonio	Texas
United States	Physician PrimeCare Research	San Antonio	Texas
United States	Institute of HealthCare Assessment, Inc.	San Diego	California
United States	S. Carolina Pharmaceutical Research	Spartanburg	South Carolina
United States	Midwest Chest Consultants	St. Charles	Missouri
United States	C.A.R.E. Clinical Research	St. Louis	Missouri
United States	DCT	Sugar Land	Texas
United States	Pulmonary Consultants, PLLC	Tacoma	Washington
United States	Clinical Research of West Florida	Tampa	Florida
United States	CU Pharmaceutical Research	Union	South Carolina
United States	Omega Medical Research	Warwick	Rhode Island
United States	SouthEast Research Institute	Webster	Texas
United States	Piedmont Medical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time From Randomization to Respiratory Death or First COPD Exacerbation Related Hospitalization (Whichever Occurs First).	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.	0-12 months	Yes
Secondary	The Incidence of Protocol Defined COPD Exacerbations.	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).	0-12 months	No
Secondary	The Incidence of All Cause Mortality	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.	0-12 months	No
Secondary	The Incidence of Treatment Emergent AEs	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.	0-12 months	No
Secondary	SGRQ: Mean Change From Baseline in Total Score	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.	Baseline and on treatment at months 3, 6 and 12 (or early termination)	No
Secondary	FEV1: Mean Change From Baseline	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.	Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)	No
Secondary	Percent Predicted FEV1: Mean Change From Baseline	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.	Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)	No
Secondary	Forced Vital Capacity (FVC): Mean Change From Baseline	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.	Baseline and on treatment at months 3, 6, 9 and 12 (or early termination)	No
Secondary	Inspiratory Capacity (IC): Mean Change From Baseline	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.	Baseline and on treatment at months 3, 6, 9 and 12 (or early termination)	No