A Pivotal Study of the Safety and Effectiveness of Arformoterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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

A 12 week study to investigate the safety and effectiveness of arformoterol given twice daily compared to placebo in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Arformoterol tartrate inhalation solution; Drug: Arformoterol tartrate inhalation solution; Drug: Arformoterol tartrate inhalation solution; Drug: Salmeterol MDI; Drug: Placebo

Detailed Description

This study is a double-blind, double-dummy, randomized, placebo- and active-controlled, multicenter, parallel-group study of adult subjects with a primary clinical diagnosis of COPD. Approximately 800 subjects were to be randomized in this study. Study participation consisted of a total of eight (8) study visits over approximately four (4) months for each subject. 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.

• Study Type: Interventional
• Enrollment (Actual): 717
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States
    • Birmingham, Alabama, United States
    • Jasper, Alabama, United States
    • Mobile, Alabama, United States
    • Oxford, Alabama, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Los Angeles, California, United States
    • Mirage, California, United States
    • Mission Hills, California, United States
    • San Diego, California, United States
    • Santa Ana, California, United States
    • Signal Hill, California, United States
  • Colorado
    • Colorado Springs, Colorado, United States
    • Denver, Colorado, United States
    • Wheat Ridge, Colorado, United States
  • Florida
    • Clearwater, Florida, United States
    • DeLand, Florida, United States
    • Miami, Florida, United States
    • Ocala, Florida, United States
    • Pensacola, Florida, United States
    • St. Petersburg, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Austell, Georgia, United States
    • Decatur, Georgia, United States
  • Illinois
    • Bloomington, Illinois, United States
  • Indiana
    • Evansville, Indiana, United States
  • Kansas
    • Shawnee Mission, Kansas, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • Charles, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • Margate, New Jersey, United States
    • South Bound Brook, New Jersey, United States
  • New Mexico
    • Alburquerque, New Mexico, United States
  • New York
    • Endwell, New York, United States
    • Ithaca, New York, United States
    • New York, New York, United States
  • North Carolina
    • Charlotte, North Carolina, United States
    • Raleigh, North Carolina, United States
    • Spartanburg, North Carolina, United States
    • Wilmington, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Oregon
    • Medford, Oregon, United States
  • Pennsylvania
    • Pittsburg, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • Texas
    • Houston, Texas, United States
    • Irving, Texas, United States
    • San Antonio, Texas, United States
  • Virginia
    • Chesapeake, Virginia, United States
    • Richmond, Virginia, United States
  • Washington
    • Tacoma, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Subject may be male or female and must be aged less than or equal to 35 years on the day the informed consent is signed.
• Female subjects greater than or equal to 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 (defined as status post-hysterectomy or bilateral tubal ligation) OR
  • postmenopausal
• Subject must have a primary diagnosis of COPD, which may include components of chronic bronchitis and/or emphysema. Diagnosis can be made during the screening process.
• Subject must have a minimum smoking history of 15 pack-years (pack-years = the number of cigarette packs per day times the number of years).
• Subject must have a chest x-ray that is consistent with the diagnosis of COPD (e.g., not diagnostic of pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions) and taken less than or equal to 3 months prior to study start. If there is no chest x-ray taken less than or equal to 3 months prior to study start, or if recent results are unavailable for review, a chest x-ray will be performed.
• Subject must be able to complete all study questionnaires and logs reliably. Exclusion Criteria
• Female subject who is pregnant or lactating.
• Subject who has 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.
• Subject who is scheduled for in-patient hospitalization, including elective surgery (in patient or out-patient) during the trial.
• Subject with life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to study start.
• Subject with a known history of asthma or any chronic respiratory disease (including a current history of sleep apnea) other than COPD (chronic bronchitis and/or emphysema).
• Subject with a history of cancer except non-melanomatous skin cancer. Subjects with a history of cancer that is considered surgically cured and without a recurrence within the past 10 years may participate in the study. History of hematologic/lymphatic malignancy treated with chemotherapy or radiation is not allowed.
• Subject with a history of lung resection of more than one full lobe.
• Subject who requires continuous supplemental oxygen therapy (unless subject resides at elevation greater than or equal to 4,000 feet).
• Subject who has had a change in dose or type of any medications for COPD within 14 days prior to the screening visit.
• Subject with a known sensitivity to (R,R)-formoterol, ipratropium, salmeterol or albuterol or any of the excipients contained in any of these formulations.
• Subject with a history of substance abuse or drug abuse within 12 months of study start, or with a positive urine drug screen at study start.
• Subject using any prescription drug for which concomitant beta-agonist administration is contraindicated (e.g., beta-blockers).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Arformoterol 50 mcg QD and placebo MDI	Drug: Arformoterol tartrate inhalation solution; Arformoterol 15 mcg BID; Other Names: Brovana; (R,R)-formoterol; Drug: Arformoterol tartrate inhalation solution; Arformoterol 25 mcg BID; Other Names: Brovana; (R,R)-formoterol; Drug: Arformoterol tartrate inhalation solution; Arformoterol 50 mcg QD; Other Names: Brovana; (R,R-)formoterol
Experimental: B; Arformoterol 25 mcg BID and placebo MDI	Drug: Arformoterol tartrate inhalation solution; Arformoterol 15 mcg BID; Other Names: Brovana; (R,R)-formoterol; Drug: Arformoterol tartrate inhalation solution; Arformoterol 25 mcg BID; Other Names: Brovana; (R,R)-formoterol; Drug: Arformoterol tartrate inhalation solution; Arformoterol 50 mcg QD; Other Names: Brovana; (R,R-)formoterol
Experimental: C; Arformoterol 15 mcg BID and placebo MDI	Drug: Arformoterol tartrate inhalation solution; Arformoterol 15 mcg BID; Other Names: Brovana; (R,R)-formoterol; Drug: Arformoterol tartrate inhalation solution; Arformoterol 25 mcg BID; Other Names: Brovana; (R,R)-formoterol; Drug: Arformoterol tartrate inhalation solution; Arformoterol 50 mcg QD; Other Names: Brovana; (R,R-)formoterol
Active Comparator: D; Salmeterol MDI 42 mcg BID and placebo inhalation solution	Drug: Salmeterol MDI; Salmeterol MDI 42 mcg BID; Other Names: Serevent
Placebo Comparator: E; Placebo BID MDI and inhalation solution	Drug: Placebo; Placebo BID MDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from study baseline FEV1 to the end of the dosing interval (12 hours post-second dose for the BID treatment arms and 24 hours post-dose for the QD treatment arm)	Weeks -2, 0, 3, 6, 9, 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Time-normalized area under the percent change from visit pre-dose curve for FEV1 over 12 hours (nAUC0-12)	Weeks -2, 0, 3, 6, 9, 12
Peak percent of predicted FEV1	Weeks -2, 0, 3, 6, 9, 12
Time-normalized area under the percent change from study baseline curve for FEV1 over 12 hours (nAUC0-12)	Weeks -2, 0, 3, 6, 9, 12
Time-normalized area under the percent change from study baseline curve for FEV1 over 24 hours (nAUC0-24)	Weeks -2, 0, 3, 6, 9, 12
Timepoint changes in FEV1	Weeks -2, 0, 3, 6, 9, 12
Time to onset of response	Weeks -2, 0, 3, 6, 9, 12
Time to peak change in FEV1	Weeks -2, 0, 3, 6, 9, 12
At-home and in-clinic peak expiratory flow rate (PEFR)	Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Ipratropium bromide MDI use	Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Racemic albuterol MDI use	Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Exacerbations of COPD	Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
COPD symptom ratings (over 12 weeks of treatment)	Weeks -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Relationship between plasma concentrations of (R,R) formoterol and selected pharmacodynamic parameters	Weeks -2, 0, 3, 6, 9, 12

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): June 1, 2003
• Study Completion (Actual): June 1, 2003

Study Registration Dates

• First Submitted: May 23, 2008
• First Submitted That Met QC Criteria: May 27, 2008
• First Posted (Estimate): May 28, 2008

Study Record Updates

• Last Update Posted (Estimate): November 2, 2012
• Last Update Submitted That Met QC Criteria: November 1, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Chronic obstructive pulmonary disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Pharmaceutical Solutions; Salmeterol Xinafoate; Formoterol Fumarate
• Other Study ID Numbers: 091-050