Study to Evaluate the Safety of Long-Term Use of Perforomist® (Formoterol Fumarate)

Study Overview
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Brief Summary
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This study is a multi-center, randomized, placebo-controlled study to evaluate the long-term safety of Perforomist® inhalation therapy in subjects with Chronic Obstructive Pulmonary Disease (COPD). Individual participation is approximately 54 weeks, including 52 weeks of double-blind treatment.

Detailed Description
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None provided.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of Long-Term Use of Perforomist® (Formoterol Fumarate) Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD

Intervention / Treatment
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* Drug: Perforomist-Placebo
* Drug: Perforomist, nebulization, COPD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the study requirements, provide written informed consent, and agree to abide by the study protocol and its restrictions Male and female subjects at least 40 years of age with a medical diagnosis of COPD (i.e. persistent presence of dyspnea, cough or sputum production and a history of exposure to risk factors for the disease, such as tobacco smoke) A current or prior history of at least 10 pack-years of cigarette smoking and a baseline breathlessness severity grade of >=2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at randomization. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the screening visit and agree to avoid becoming pregnant for the duration of study by using adequate contraception at study entry and throughout the trial. WOCBP will be advised to notify the Investigator of any change in their pregnancy status. WOCBP include: any female who has experienced menarche and is not post-menopausal (defined as amenorrhea for at least 12 consecutive months), or has not undergone surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation). Women who are using acceptable contraceptive medications or devices to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy) will be considered WOCBP. Able to complete all aspects of the study through the end of the study, including all visits and tests, and self-administration of study medications. Exclusion Criteria: A medical diagnosis of asthma. Indication of a past history of asthma that is deemed inaccurate to a subject's current condition by the Investigator must be adequately addressed in the medical history. Clinically significant abnormal chest x-ray (CXR) (within the past 12 months) diagnostic of active/significant disease other than COPD. Evidence of any unstable or clinically significant hematopoietic, malignant, cardiovascular, hepatic, renal, neurologic, psychiatric, autoimmune disorder, or condition or disease other than COPD that, in the opinion of the Investigator, could place the subject at increased risk of complications, interfere with study participation, or confound any of the study objectives. Subjects who had radiation or chemotherapy within the previous 12 months. An abnormal laboratory test at screening deemed clinically significant and exclusionary by the Investigator. A history of hypersensitivity to study drugs or their components, including albuterol rescue. -

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perforomist, nebulization, COPD<br>Active | Drug: Perforomist, nebulization, COPD<br>* Perforomist, 20 mcg/2 mL, twice daily for 52 weeks<br>* Other names: Formoterol fumarate;|
| Placebo Comparator: Perforomist-Placebo<br>Placebo | Drug: Perforomist-Placebo<br>* Placebo vehicle, 2mL, twice daily for 52 weeks<br>* Other names: Perforomist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Primary Event of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation | The primary endpoint was the combined incidence of respiratory death, first COPD-related ER visit or first COPD exacerbation-related hospitalization (whichever occurred first from the time of randomization to the end of the study). The time-to-first event was measured and analyzed in units of weeks and was summarized by treatment for subjects in the Safety Set. An independent Mortality Adjudication Board was used to evaluate all deaths that occurred in the study and for assigning cause of death and COPD-relatedness. | 0 to 52 weeks | 
| Kaplan-Meier Probability of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation at 52 Weeks | The primary endpoint was the combined incidence of respiratory death, first COPD-related ER visit or first COPD exacerbation-related hospitalization (whichever occurred first from the time of randomization to the end of the study). The time-to-first event was measured and analyzed in units of weeks and was summarized by treatment for subjects in the Safety Set. An independent Mortality Adjudication Board was used to evaluate all deaths that occurred in the study and for assigning cause of death and COPD-relatedness. | 0 to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | An independent Mortality Adjudication Board was used to evaluate all deaths that occurred in the study and for assigning cause of death and COPD-relatedness. | 0 to 52 weeks | 
| Individual Components of the Primary Composite Endpoint - First COPD-related ER Visit and First COPD Exacerbation-Related Hospitalization |  | 0 to 52 weeks | 
| Number of Subjects With Protocol-Defined COPD Exacerbation | COPD exacerbations were defined as events in the natural course of disease characterized by an increase from baseline in two of the following symptoms: dyspnea, cough, and sputum production that was beyond normal day-to-day variations, was acute in onset, that persisted for at least two consecutive days, and that warranted a change in their regular medication. The change could be either the initiation of additional treatment(s) or the intensification of a treatment the subject was already receiving, and the change must have been specifically to address the exacerbation event. COPD exacerbations occurring after the time of withdrawal or completion of the study were not included. | 0 to 52 weeks | 
| Kaplan-Meier Probability of Protocol Defined COPD Exacerbation at 52 Weeks | COPD exacerbations were defined as events in the natural course of disease characterized by an increase from baseline in two of the following symptoms: dyspnea, cough, and sputum production that was beyond normal day-to-day variations, was acute in onset, that persisted for at least two consecutive days, and that warranted a change in their regular medication.The change could be either the initiation of additional treatment(s) or the intensification of a treatment the subject was already receiving, and the change must have been specifically to address the exacerbation event. COPD exacerbations occurring after the time of withdrawal or completion of the study were not included. | 0 to 52 weeks | 
| FEV1 Changes From Baseline at Months 3, 6, 9 and 12 |  | On treatment at months 3, 6, 9 and 12 | 
| FVC Changes From Baseline at Months 3, 6, 9 and 12 |  | On treatment at months 3, 6, 9 and 12 | 
| IC Changes From Baseline at Months 3, 6, 9 and 12 |  | On treatment at months 3, 6, 9 and 12 | 
| Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Saint Georges Respiratory Questionnaire comprises 50 items in 3 sections, Symptoms, Activity, Impact, measuring health status in chronic airflow limitation. Symptoms captures level of symptomatology. Activity and Impact responses are either yes or no. Scoring is from 0 to 100; 0 = no life quality impairment. A summary score for all items is calculated and ranges from 0 to 100, where 0 indicates best possible health status, 100 represents worst possible health status. Scores are calculated using weights attached to each item in the questionnaire - 4 unit changes are clinically meaningful. | On treatment at months 3, 6, 9 and 12 | 
| Transition Dyspnea Index | The Transition Dyspnea Index (TDI) measures changes in dyspnea severity from the baseline as established by the BDI. It has 3 components: change in functional impairment, change in magnitude of task, and change in magnitude of effort, and each component is rated on a scale ranging from -3 (major deterioration) to +3 (major improvement). The 3 components are summed to provide a total score ranging from -9 to +9. The lower the score, the more deterioration in severity of dyspnea. | On treatment at months 3, 6, 9 and 12 | 
| Health Care Utilization and Economic Impact - Number of Emergency Department Visits |  | 0 to 52 weeks | 
| Summary of Subjects Requiring Intubation or Non-Invasive Ventilation |  | 0 to 52 weeks | 
| Rescue Medication Usage | Number of puffs of rescue medication (albuterol pMDI) used per day | 0 to 52 weeks |