Clinical trial NCT00909779: Safety Study of Arformoterol Tartrate Inhalation Solution in Chronic Obstructive Pulmonary Disease (COPD) Subjects
Official title: A Large Simple Safety Study of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Chronic obstructive pulmonary disease (COPD)
respiratory
long-acting beta agonist (LABA)
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2009-05-28
Enrollment: 841
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time From Randomization to Respiratory Death or First COPD Exacerbation Related Hospitalization (Whichever Occurs First).
timeFrame: 0-12 months
Secondary outcomes:
measure: The Incidence of Protocol Defined COPD Exacerbations.
timeFrame: 0-12 months
measure: The Incidence of All Cause Mortality
timeFrame: 0-12 months
measure: The Incidence of Treatment Emergent AEs
timeFrame: 0-12 months
measure: SGRQ: Mean Change From Baseline in Total Score
timeFrame: Baseline and on treatment at months 3, 6 and 12 (or early termination)
measure: FEV1: Mean Change From Baseline
timeFrame: Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)
measure: Percent Predicted FEV1: Mean Change From Baseline
timeFrame: Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)
measure: Forced Vital Capacity (FVC): Mean Change From Baseline
timeFrame: Baseline and on treatment at months 3, 6, 9 and 12 (or early termination)
measure: Inspiratory Capacity (IC): Mean Change From Baseline
timeFrame: Baseline and on treatment at months 3, 6, 9 and 12 (or early termination)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Jefferson Clinic
state: Alabama
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutic, LLC
state: Alabama
city: Brimingham
country: United States
facility: Achieve Clinical Research
state: Alabama
city: Jasper
country: United States
facility: Jasper Summit Research, LLC
state: Alabama
city: Anaheim
country: United States
facility: Chest Critical Care Consultants
state: California
city: Fullerton
country: United States
facility: California Research Medical Group
state: California
city: Riverside
country: United States
facility: Integrated Research Group
state: California
city: Roseville
country: United States
facility: Quality Control Research Inc.
state: California
city: Sacramento
country: United States
facility: Sockolov and Sockolov APC
state: California
city: Sacremento
country: United States
facility: Centers for Clinical Trials of Sacremento
state: California
city: San Diego
country: United States
facility: Institute of HealthCare Assessment, Inc.
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chiefland
country: United States
facility: Southeast Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Tampa Bay Medical Research Inc.
state: Florida
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: The Lung Clinic, P.A.
state: Florida
city: Orlando
country: United States
facility: DCT
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Canton
country: United States
state: Georgia
city: Columbus
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Decatur
country: United States
facility: Atlanta Pharmaceutical Research
state: Georgia
city: Marietta
country: United States
facility: Wellstar Marietta Pulmonary Medicine
state: Georgia
city: Rincon
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Evansville
country: United States
facility: Medisphere Medical Research Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Hazard
country: United States
facility: Kentucky Lung Clinic
state: Kentucky
city: Lafayette
country: United States
facility: Bendel Medical Research Center, LLC
state: Louisiana
city: Ann Arbor
country: United States
facility: ClinSite LLC
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute Inc.
state: Minnesota
city: St. Charles
country: United States
facility: Midwest Chest Consultants
state: Missouri
city: St. Louis
country: United States
facility: C.A.R.E. Clinical Research
state: Missouri
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Cherry Hill
country: United States
facility: Delaware Valley Clinical Research
state: New Jersey
city: New York
country: United States
facility: New York Pulmonary and Clinical Care Associates, PC
state: New York
city: Newburgh
country: United States
facility: ENT & Allergy Associates
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Charlotte
country: United States
facility: American Health Research Inc.
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research
state: North Carolina
city: Akron
country: United States
facility: DayStar Clinical Research, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center
state: Ohio
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Portland
country: United States
facility: Allergy Associates Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Arcuri Clinical Research, LLC
state: Pennsylvania
city: Pawtucket
country: United States
facility: Biomedical Research Alliance at Hypertension and Nephrology
state: Rhode Island
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Charleston
country: United States
facility: Lowcountry Lung & Critical Care, PA
state: South Carolina
city: Columbia
country: United States
facility: Neem Research Group, Inc.
state: South Carolina
city: Gaffney
country: United States
facility: Gaffney Pharmaceutical Research
state: South Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research
state: South Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research, Inc.
state: South Carolina
city: Spartanburg
country: United States
facility: S. Carolina Pharmaceutical Research
state: South Carolina
city: Union
country: United States
facility: CU Pharmaceutical Research
state: South Carolina
city: Knoxville
country: United States
facility: Allergy Associates
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Arlington
country: United States
facility: DCT
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, Clinical Studies Unit, Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: VAMC
state: Texas
city: Kingwood
country: United States
facility: Kingwood Research Institute, LLC
state: Texas
city: San Antonio
country: United States
facility: Physician PrimeCare Research
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: Sugar Land
country: United States
facility: DCT
state: Texas
city: Webster
country: United States
facility: SouthEast Research Institute
state: Texas
city: Provo
country: United States
facility: National Clinical Resources, Inc.
state: Utah
city: Salt Lake City
country: United States
facility: Utah Clinical Trials LLC
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Inc.
state: Virginia
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Richmond
country: United States
facility: Dominion Medical Associates
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond Inc.
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
city: Tacoma
country: United States
facility: Pulmonary Consultants, PLLC
state: Washington
Study officials:
References:
citation: Donohue JF, Ganapathy V, Bollu V, Stensland MD, Nelson LM. Health Status of Patients with Moderate to Severe COPD after Treatment with Nebulized Arformoterol Tartrate or Placebo for 1 Year. Clin Ther. 2017 Jan;39(1):66-74. doi: 10.1016/j.clinthera.2016.11.021. Epub 2016 Dec 20.
citation: Donohue JF, Hanania NA, Make B, Miles MC, Mahler DA, Curry L, Tosiello R, Wheeler A, Tashkin DP. One-year safety and efficacy study of arformoterol tartrate in patients with moderate to severe COPD. Chest. 2014 Dec;146(6):1531-1542. doi: 10.1378/chest.14-0117.