Safety and Efficacy of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease
- Conditions
- Chronic Obstructive Pulmonary DiseaseEmphysemaBronchitis
- Interventions
- Registration Number
- NCT00250679
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 443
- 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)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Formoterol 12 ųg 2x/day Placebo - Arformoterol 25 ųg 2x/day Placebo - Formoterol 12 ųg 2x/day Formoterol 12 ųg BID - Arformoterol 15 ųg 2x/day Arformoterol tartrate inhalation solution - Arformoterol 25 ųg 2x/day Arformoterol 25 ųg BID - Arformoterol 15 ųg 2x/day Placebo -
- Primary Outcome Measures
Name Time Method Percent (%) of Participants With Adverse Events (AEs), in Particular COPD Exacerbations Six months Percent of participants with the adverse event specified.
SOC = system organ class.
- Secondary Outcome Measures
Name Time Method Transitional (Relative Change in) Dyspnea Index weeks 13, 26 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.
6-Minute Walk: Change From Baseline in the Distance Walked in 6 Minutes Post-Dose weeks 0, 13, 26 Mean change from baseline in distance walked (meters)
6-Hour Peak Changes From Baseline in Forced Expiratory Volume (FEV1) weeks 0,3,13,26 The 6 hour peak change from baseline is the maximum of the post-dose change values through 6 hours at each visit.
Time-Normalized Area Under the Curve (nAUC) From 0 to 6 Hrs for Forced Expiratory Volume in One Second (FEV1) Changes From Baseline weeks 0,3,13,26 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.
Number of Participants With Potentially Clinically Significant Heart Rate visit 6 (week 27) 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)
Number of Participants With New 24-Hour Holter Monitoring Alerts Visit 6 (week 27) 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 visit 6 (week 27) 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 visit 6 (week 27) Patients with potassium values that met low (\<=3 mEq/L) or high (\>=6 mEq/L) criteria were considered potentially clinically significant.
Ipratropium Bromide Metered Dose Inhaler (MDI) Usage: Days Used Per Week Screening (day-14 to 0) and Treatment (week 0 - 26) 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 Screening (day-14 to 0) and Treatment (week 0 - 26) Supplemental medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication.
Forced Expiratory Volume in One Second (FEV1) Changes From Baseline for 24 Hour Post Dose Timepoint (Trough) weeks 0,3,13,26 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 weeks 13, 26 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.
Modified Medical Research Council Dyspnea Questionaire Baseline (visit 2), weeks 13, 26 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 visits 4 (week 13), visit 5 (week 26) 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.
Mean Values for the 6-Minute Walk Test: Distance Walked in Meters Baseline (Visit 2), week 13, week 26 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 Baseline (Visit 2), Weeks 13, 26 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 Baseline (Visit 2), weeks 13, 26 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 Baseline (Visit 2), weeks 13, 26 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 Forced Expiratory Volume in One Second (FEV1) Baseline (Visit 2), weeks 3, 13, 26 Forced Expiratory Volume in one second
Number of Participants With New 12-Lead Electrocardiogram (ECG) Alerts visit 6 (week 27) New Electrocardiogram (ECG) alerts are defined as those alerts that occurred post-treatment and were not present at baseline.
Inspiratory Capacity Changes From Baseline weeks 0,3,13,26 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.
Racemic Albuterol or Levalbuterol Metered Dose Inhaler (MDI) Usage: Days Used Per Week Screening (day-14 to 0) and Treatment (week 0 - 26) 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 Screening (day-14 to 0) and Treatment (week 0 - 26) Rescue medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication.
Investigator Global Evaluations Change From Baseline weeks 13, 26 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 Baseline (visit 2), weeks 13, 26 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.
Mean Change From Baseline in St. George's Respiratory Questionnaire weeks 13, 26 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 Visit 4 (week 13) , Visit 5 (week 26) 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.
Number of Participants With an Improved Transitional Dyspnea Index weeks 13, 26 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.
Percent (%) of Participants With a >=4 Unit Improvement in the St. George's Respiratory Questionaire visit 4 (week 13), visit 5 (week 26) 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 Inspiratory Capacity Baseline (Visit 2), Weeks 3, 13, 26 Inspiratory capacity is the maximum volume that can be inhaled.