Safety and Efficacy of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT00250679
First received: November 4, 2005
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

To evaluate the long-term safety and monitor the long-term efficacy of arformoterol over a period of 6 months in subjects with chronic obstructive pulmonary disease (COPD).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Bronchitis
Emphysema
Drug: Arformoterol tartrate inhalation solution
Drug: Arformoterol 25 ųg BID
Drug: Formoterol 12 ųg BID
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter, Double-Blind, Double-Dummy, Randomized, Active-Controlled, Parallel Group Long-Term Safety Study of 15 μg and 25 μg Arformoterol Tartrate Inhalation Solution BID in Subjects With Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations [ Time Frame: Six months ] [ Designated as safety issue: Yes ]

    Percent of participants with the adverse event specified.

    SOC = system organ class.



Secondary Outcome Measures:
  • Number of Participants With New 24-Hour Holter Monitoring Alerts [ Time Frame: Visit 6 (week 27) ] [ Designated as safety issue: No ]
    New holter monitoring alerts are defined as those alerts that occurred post-randomization and were not present at baseline.

  • Number of Participants With Potentially Clinically Significant Glucose Evaluations [ Time Frame: visit 6 (week 27) ] [ Designated as safety issue: No ]
    Patients with glucose values that met low (<=40 mg/dL) or high (>=175 mg/dL) criteria were considered potentially clinically significant.

  • Number of Participants With Potentially Clinically Significant Potassium Evaluations [ Time Frame: visit 6 (week 27) ] [ Designated as safety issue: No ]
    Patients with potassium values that met low (<=3 mEq/L) or high (>=6 mEq/L) criteria were considered potentially clinically significant.

  • Number of Participants With New 12-Lead Electrocardiogram (ECG) Alerts [ Time Frame: visit 6 (week 27) ] [ Designated as safety issue: No ]
    New Electrocardiogram (ECG) alerts are defined as those alerts that occurred post-treatment and were not present at baseline.

  • Inspiratory Capacity Changes From Baseline [ Time Frame: weeks 0,3,13,26 ] [ Designated as safety issue: No ]
    Mean Change in Inspiratory Capacity values from baseline (baseline assessment obtained at Visit 2, pre-dose). Spirometry measurements collected within 6 hours following in-clinic rescue/supplemental medications use were excluded from analysis.

  • 6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) [ Time Frame: weeks 0,3,13,26 ] [ Designated as safety issue: No ]
    The 6 hour peak change from baseline is the maximum of the post-dose change values through 6 hours at each visit.

  • Number of Participants With Potentially Clinically Significant Heart Rate [ Time Frame: visit 6 (week 27) ] [ Designated as safety issue: No ]
    Number of subjects with a heart rate that was lower/higher than a set limit and increased/decreased from set baseline limit in beats per minute (bpm)

  • Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Days Used Per Week [ Time Frame: Screening (day-14 to 0) and Treatment (week 0 - 26) ] [ Designated as safety issue: No ]
    Supplemental medication usage is recorded throughout the study. MDI stands for metered dose inhaler.

  • Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day [ Time Frame: Screening (day-14 to 0) and Treatment (week 0 - 26) ] [ Designated as safety issue: No ]
    Supplemental medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication.

  • Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Days Used Per Week [ Time Frame: Screening (day-14 to 0) and Treatment (week 0 - 26) ] [ Designated as safety issue: No ]
    Rescue medication usage during the study. MDI stands for metered dose inhaler.

  • Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Number of Actuations Per Day [ Time Frame: Screening (day-14 to 0) and Treatment (week 0 - 26) ] [ Designated as safety issue: No ]
    Rescue medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication.

  • Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline [ Time Frame: weeks 0,3,13,26 ] [ Designated as safety issue: No ]
    Area under the change from baseline curve from 0 to 6 hours. Time-normalized AUC (0-6 hrs) was derived using the linear trapezoidal method.

  • Transitional (Relative Change in) Dyspnea Index [ Time Frame: weeks 13, 26 ] [ Designated as safety issue: No ]
    The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A Transitional Dyspnea Index score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests.

  • Number of Participants With an Improved Transitional Dyspnea Index [ Time Frame: weeks 13, 26 ] [ Designated as safety issue: No ]
    The number of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score compares current health against baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement.

  • Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) [ Time Frame: weeks 0,3,13,26 ] [ Designated as safety issue: No ]
    The 24 hour trough is the FEV1 value obtained 24 hours post first dose. This value is compared to the baseline FEV1 value.

  • Subject Global Evaluations Change From Baseline [ Time Frame: weeks 13, 26 ] [ Designated as safety issue: No ]
    The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1=much better and 7=much worse. Ratings were assessed relative to the subject's initial entry into the study.

  • Investigator Global Evaluations Change From Baseline [ Time Frame: weeks 13, 26 ] [ Designated as safety issue: No ]
    The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. Ratings were assessed relative to the subject's initial entry into the study.

  • BODE Index [ Time Frame: Baseline (visit 2), weeks 13, 26 ] [ Designated as safety issue: No ]
    The BODE index (0=relative health and 10=severe chronic obstructive pulmonary disease) is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the 6-minute walk test. Scores were derived using pre-dose assessments from each visit.

  • 6-Minute Walk: Change From Baseline in the Distance Walked in 6 Minutes [ Time Frame: Post-Dose weeks 0, 13, 26 ] [ Designated as safety issue: No ]
    Mean change from baseline in distance walked (meters)

  • Mean Change From Baseline in St. George's Respiratory Questionnaire [ Time Frame: weeks 13, 26 ] [ Designated as safety issue: No ]
    Scores are expressed as a mean change from baseline of overall impairment (total score). The questionnaire has a scale of 100 which represents worst possible health status to 0 which indicates best possible health status.

  • Number of Participants With a >=4 Unit Improvement on the St. George's Respiratory Questionnaire [ Time Frame: Visit 4 (week 13) , Visit 5 (week 26) ] [ Designated as safety issue: No ]
    Scores are expressed as the number of participants with >= 4 unit improvement in overall impairment (total score), where 100 represents worst possible health status and 0 indicates best possible health status.

  • Modified Medical Research Council Dyspnea Questionaire [ Time Frame: Baseline (visit 2), weeks 13, 26 ] [ Designated as safety issue: No ]
    Scores range from 0 to 4, with a score of 4 indicating that a subject is too breathless to leave the house or becomes breathless when dressing or undressing. The highest numbered question to which the subject answered 'Yes' is the Dyspnea Scale Score.

  • Percent (%) of Participants With an Improved Transitional Dyspnea Index [ Time Frame: visits 4 (week 13), visit 5 (week 26) ] [ Designated as safety issue: No ]
    The percentage of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score is the sum of the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement.

  • Percent (%) of Participants With a >=4 Unit Improvement in the St. George's Respiratory Questionaire [ Time Frame: visit 4 (week 13), visit 5 (week 26) ] [ Designated as safety issue: No ]
    Percent of participants with a >=4 unit improvement in the overall impairment (total score) of the St. George's Respiratory Questionaire. This questionaire uses a 100 - 0 scale, where 100 represents the worst possible health status and 0 indicates the best possible health status.

  • Mean Values for the 6-Minute Walk Test: Distance Walked in Meters [ Time Frame: Baseline (Visit 2), week 13, week 26 ] [ Designated as safety issue: No ]
    This test measures the participants' level of fitness. It is a measure of the distance the participant can walk in 6 minutes.

  • Mean Values for Investigator Global Evaluations [ Time Frame: Baseline (Visit 2), Weeks 13, 26 ] [ Designated as safety issue: No ]
    The investigator global evaluation is reported by the study investigator. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse.

  • Mean Values for St. George's Respiratory Questionnaire [ Time Frame: Baseline (Visit 2), weeks 13, 26 ] [ Designated as safety issue: No ]
    A questionnaire to assess respiratory health. Scores are expressed as a percentage of overall impairment (total score), where 100 represents the worst possible health status and 0 indicates best possible health status.

  • Mean Values for Subject Global Evaluations [ Time Frame: Baseline (Visit 2), weeks 13, 26 ] [ Designated as safety issue: No ]
    The subject global evaluation is reported by study subjects/participants. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse.

  • Mean Values for Inspiratory Capacity [ Time Frame: Baseline (Visit 2), Weeks 3, 13, 26 ] [ Designated as safety issue: No ]
    Inspiratory capacity is the maximum volume that can be inhaled.

  • Mean Values for Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline (Visit 2), weeks 3, 13, 26 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in one second


Enrollment: 443
Study Start Date: October 2005
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Formoterol 12 ųg 2x/day Drug: Formoterol 12 ųg BID
Formoterol fumarate 12 ųg BID via aerolizer/DPI
Other Names:
  • Foradil
  • R,S-formoterol
Drug: Placebo
Placebo nebule or placebo aerolizer
Other Name: placebo
Experimental: Arformoterol 15 ųg 2x/day Drug: Arformoterol tartrate inhalation solution
Arformoterol 15 ųg BID by nebulization
Other Name: Brovana®
Drug: Placebo
Placebo nebule or placebo aerolizer
Other Name: placebo
Experimental: Arformoterol 25 ųg 2x/day Drug: Arformoterol 25 ųg BID
Arformoterol 25 ųg BID by nebulization
Other Names:
  • Brovana
  • R,R formoterol
Drug: Placebo
Placebo nebule or placebo aerolizer
Other Name: placebo

Detailed Description:

This is a double-blind, double-dummy, multicenter, randomized, active-controlled, parallel group, outpatient, safety study to evaluate the long term safety of arformoterol in the treatment of subjects with COPD. Study participation will be over approximately 6 months. 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

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male and female subjects must be at least 35 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 >=15 pack-year smoking history and a baseline breathlessness severity grade of >=2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visits 1 and 2
  • Female subjects <=65 years of age must have a negative serum pregnancy test, females of childbearing potential must be using an acceptable method of birth control
  • Subjects must be in general good health.

Key Exclusion criteria:

  • 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 have had a febrile illness within 72 hours (3 days) before Screening Visit 1
  • Subjects with a chest x-ray that suggests a diagnosis other than COPD (e.g., diagnostic of pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00250679

  Show 60 Study Locations
Sponsors and Collaborators
Sunovion
Investigators
Study Director: Sepracor Medical Director Sunovion
  More Information

Additional Information:
Publications:
Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT00250679     History of Changes
Other Study ID Numbers: 091-061
Study First Received: November 4, 2005
Results First Received: October 3, 2008
Last Updated: May 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sunovion:
COPD
chronic bronchitis
emphysema

Additional relevant MeSH terms:
Bronchitis
Emphysema
Pulmonary Emphysema
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Pathologic Processes
Pharmaceutical Solutions
Formoterol
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014