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

NCT00909779 | Completed Phase 3 Results DMC

• 1 other identifier: 091-080
• Study Type: interventional
• Target: 841
• Locations: 1 country
• Sites: 73

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic obstructive pulmonary disease (COPD); respiratory; long-acting beta agonist (LABA)

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• The Incidence of Protocol Defined COPD Exacerbations.

  0-12 months

• The Incidence of All Cause Mortality

  0-12 months

• The Incidence of Treatment Emergent AEs

  0-12 months

• SGRQ: Mean Change From Baseline in Total Score

  Baseline and on treatment at months 3, 6 and 12 (or early termination)

• FEV1: Mean Change From Baseline

  Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)

Study Arms (2)

Arformoterol 15 mcg twice daily

EXPERIMENTAL

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.

Drug: Arformoterol

Placebo twice daily

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Arformoterol DRUG

Arformoterol Tartrate Inhalation Solution 15 mcg twice daily (BID) for a duration of one year

Also known as: Brovana

Arformoterol 15 mcg twice daily

Placebo DRUG

Placebo inhalation solution, twice daily (BID) for a duration of one year.

Placebo twice daily

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (73)

Jefferson Clinic

Birmingham, Alabama, 25233, United States

Location

Alabama Clinical Therapeutic, LLC

Birmingham, Alabama, 35235, United States

Location

Achieve Clinical Research

Brimingham, Alabama, 35209, United States

Location

Jasper Summit Research, LLC

Jasper, Alabama, 35501, United States

Location

Chest Critical Care Consultants

Anaheim, California, 92801, United States

Location

California Research Medical Group

Fullerton, California, 92835, United States

Location

Integrated Research Group

Riverside, California, 92506, United States

Location

Quality Control Research Inc.

Roseville, California, 95661, United States

Location

Sockolov and Sockolov APC

Sacramento, California, 95825, United States

Location

Centers for Clinical Trials of Sacremento

Sacremento, California, 95823, United States

Location

Institute of HealthCare Assessment, Inc.

San Diego, California, 92120, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Southeast Clinical Research

Chiefland, Florida, 32626, United States

Location

Tampa Bay Medical Research Inc.

Clearwater, Florida, 33761, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Avail Clinical Research

DeLand, Florida, 32720, United States

Location

The Lung Clinic, P.A.

Kissimmee, Florida, 34741, United States

Location

DCT

Orlando, Florida, 32806, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33603, United States

Location

Unknown Facility

Canton, Georgia, 30114, United States

Location

Southeast Regional Research Group

Columbus, Georgia, 31904, United States

Location

Atlanta Pharmaceutical Research

Decatur, Georgia, 30033, United States

Location

Wellstar Marietta Pulmonary Medicine

Marietta, Georgia, 30060, United States

Location

Southeast Regional Research Group

Rincon, Georgia, 31326, United States

Location

Medisphere Medical Research Center

Evansville, Indiana, 47714, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Kentucky Lung Clinic

Hazard, Kentucky, 41701, United States

Location

Bendel Medical Research Center, LLC

Lafayette, Louisiana, 70503, United States

Location

ClinSite LLC

Ann Arbor, Michigan, 48106, United States

Location

Clinical Research Institute Inc.

Minneapolis, Minnesota, 55402, United States

Location

Midwest Chest Consultants

Saint Charles, Missouri, 63301, United States

Location

C.A.R.E. Clinical Research

St Louis, Missouri, 63141, United States

Location

Comprehensive Clinical Research

Berlin, New Jersey, 08009, United States

Location

Delaware Valley Clinical Research

Cherry Hill, New Jersey, 08003, United States

Location

New York Pulmonary and Clinical Care Associates, PC

New York, New York, 10016, United States

Location

ENT & Allergy Associates

Newburgh, New York, 12550, United States

Location

Rochester Clinical Research

Rochester, New York, 14609, United States

Location

AAIR Research Center

Rochester, New York, 14618, United States

Location

American Health Research Inc.

Charlotte, North Carolina, 28207, United States

Location

Piedmont Medical Research

Winston-Salem, North Carolina, 27103, United States

Location

DayStar Clinical Research, Inc.

Akron, Ohio, 44313, United States

Location

Bernstein Clinical Research Center

Cincinnati, Ohio, 45231, United States

Location

Clinical Research Institute of Southern Oregon, PC

Medford, Oregon, 97504, United States

Location

Allergy Associates Research Center

Portland, Oregon, 97216, United States

Location

Arcuri Clinical Research, LLC

Philadelphia, Pennsylvania, 19142, United States

Location

Biomedical Research Alliance at Hypertension and Nephrology

Pawtucket, Rhode Island, 02860, United States

Location

Omega Medical Research

Warwick, Rhode Island, 02886, United States

Location

Lowcountry Lung & Critical Care, PA

Charleston, South Carolina, 29406, United States

Location

Neem Research Group, Inc.

Columbia, South Carolina, 29201, United States

Location

Gaffney Pharmaceutical Research

Gaffney, South Carolina, 29340, United States

Location

Greenville Pharmaceutical Research

Greenville, South Carolina, 29615, United States

Location

Upstate Pharmaceutical Research

Greenville, South Carolina, 29615, United States

Location

Mountain View Clinical Research, Inc.

Greer, South Carolina, 29651, United States

Location

S. Carolina Pharmaceutical Research

Spartanburg, South Carolina, 29303, United States

Location

CU Pharmaceutical Research

Union, South Carolina, 29379, United States

Location

Allergy Associates

Knoxville, Tennessee, 37909, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

DCT

Arlington, Texas, 76014, United States

Location

Baylor College of Medicine, Clinical Studies Unit, Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

VAMC

Houston, Texas, 77030, United States

Location

Kingwood Research Institute, LLC

Kingwood, Texas, 77339, United States

Location

Physician PrimeCare Research

San Antonio, Texas, 78212, United States

Location

Diagnostics Research Group

San Antonio, Texas, 78229, United States

Location

DCT

Sugar Land, Texas, 77878, United States

Location

SouthEast Research Institute

Webster, Texas, 77598, United States

Location

National Clinical Resources, Inc.

Provo, Utah, 84604, United States

Location

Utah Clinical Trials LLC

Salt Lake City, Utah, 84107, United States

Location

Charlottesville Medical Research Inc.

Charlottesville, Virginia, 22911, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Dominion Medical Associates

Richmond, Virginia, 23219, United States

Location

Pulmonary Associates of Richmond Inc.

Richmond, Virginia, 23225, United States

Location

Pulmonary Associates of Richmond, Inc.

Richmond, Virginia, 23229, United States

Location

Pulmonary Consultants, PLLC

Tacoma, Washington, 98405, United States

Location

Related Publications (2)

• 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.

  PMID: 28011247 DERIVED

• 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.

  PMID: 25451347 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Limitations and Caveats

Although LABAs other than study medication were discontinued, other medications were not controlled for. A large number of subjects discontinued after a primary event and their eventual outcomes are unknown.

Results Point of Contact

• Title: Respiratory Medical Director
• Organization: Sunovion

1-866-503-6351

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2009
• First Posted: May 28, 2009
• Study Start: June 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: November 11, 2013
• Results First Posted: November 11, 2013

Record last verified: 2013-09

Locations

US (73)