COPD
Conditions
Brief summary
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
None provided.
Interventions
DRUGPerforomist-Placebo
Placebo vehicle, 2mL, twice daily for 52 weeks
DRUGPerforomist, nebulization, COPD
Perforomist, 20 mcg/2 mL, twice daily for 52 weeks
Sponsors
Dey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to understand the study requirements, provide written informed consent, and agree to abide by the study protocol and its restrictions 2. 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) 3. 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. 4. 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. 5. 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
1. 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. 2. Clinically significant abnormal chest x-ray (CXR) (within the past 12 months) diagnostic of active/significant disease other than COPD. 3. 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. 4. Subjects who had radiation or chemotherapy within the previous 12 months. 5. An abnormal laboratory test at screening deemed clinically significant and exclusionary by the Investigator. 6. A history of hypersensitivity to study drugs or their components, including albuterol rescue. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With a Primary Event of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation | 0 to 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. |
| Kaplan-Meier Probability of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation at 52 Weeks | 0 to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | On treatment at months 3, 6, 9 and 12 | — |
| Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | 0 to 52 weeks | 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. |
| 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 | 0 to 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. |
| Kaplan-Meier Probability of Protocol Defined COPD Exacerbation at 52 Weeks | 0 to 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. |
| FVC Changes From Baseline at Months 3, 6, 9 and 12 | On treatment at months 3, 6, 9 and 12 | — |
| Transition Dyspnea Index | On treatment at months 3, 6, 9 and 12 | 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. |
| 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 | 0 to 52 weeks | Number of puffs of rescue medication (albuterol pMDI) used per day |
| Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | On treatment at months 3, 6, 9 and 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. |
| IC Changes From Baseline at Months 3, 6, 9 and 12 | On treatment at months 3, 6, 9 and 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perforomist Inhalation Solution Active
Perforomist Inhalation Solution, 20mcg/2 mL, twice daily nebulization for 52 weeks | 541 |
| Matching Placebo Placebo
Perforomist Matching Placebo: placebo vehicle, 2mL, twice daily nebulization for 52 weeks | 530 |
| Total | 1,071 |
Baseline characteristics
| Characteristic | Total | Matching Placebo | Perforomist Inhalation Solution |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.09 | 62.5 years STANDARD_DEVIATION 9.17 | 62.7 years STANDARD_DEVIATION 9.01 |
| Baseline Dyspnea Index | 6.2 units on a scale STANDARD_DEVIATION 1.99 | 6.2 units on a scale STANDARD_DEVIATION 1.99 | 6.1 units on a scale STANDARD_DEVIATION 1.99 |
| Baseline FEV1 | 1.2707 Litres STANDARD_DEVIATION 0.49073 | 1.2926 Litres STANDARD_DEVIATION 0.50496 | 1.2494 Litres STANDARD_DEVIATION 0.47593 |
| Baseline FVC | 2.451 Litres STANDARD_DEVIATION 0.76373 | 2.4740 Litres STANDARD_DEVIATION 0.78394 | 2.4276 Litres STANDARD_DEVIATION 0.74347 |
| Baseline IC | 1.9619 Litres STANDARD_DEVIATION 0.66734 | 1.9783 Litres STANDARD_DEVIATION 0.66897 | 1.9458 Litres STANDARD_DEVIATION 0.66598 |
| Baseline % Predicted FEV1 | 44.35 % STANDARD_DEVIATION 13.226 | 44.89 % STANDARD_DEVIATION 13.787 | 43.82 % STANDARD_DEVIATION 12.646 |
| Baseline Saint Georges Respiratory Questionnaire Score | 52.992 units on a scale STANDARD_DEVIATION 16.9756 | 52.550 units on a scale STANDARD_DEVIATION 16.9953 | 53.429 units on a scale STANDARD_DEVIATION 16.9607 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants | 26 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1016 Participants | 504 Participants | 512 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of Pack Years | 43.00 Pack Years | 44.00 Pack Years | 41 Pack Years |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 5 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 97 Participants | 46 Participants | 51 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 961 Participants | 478 Participants | 483 Participants |
| Region of Enrollment United States | 1071 Participants | 530 Participants | 541 Participants |
| Screening COPD Severity (GOLD) n (%) Moderate (% Predicted FEV1 50 to <80%) | 547 Participants | 273 Participants | 274 Participants |
| Screening COPD Severity (GOLD) n (%) Not Reported/Unknown | 6 Participants | 3 Participants | 3 Participants |
| Screening COPD Severity (GOLD) n (%) Severe (% Predicted FEV1 30 to <50%) | 511 Participants | 250 Participants | 261 Participants |
| Screening COPD Severity (GOLD) n (%) Very Severe (% Predicted FEV1 <30%) | 7 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Female | 552 Participants | 267 Participants | 285 Participants |
| Sex: Female, Male Male | 519 Participants | 263 Participants | 256 Participants |
| Smoking Status n (%) Current Smoker | 560 Participants | 278 Participants | 282 Participants |
| Smoking Status n (%) Ex-smoker | 511 Participants | 252 Participants | 259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 541 | 10 / 530 |
| other Total, other adverse events | 374 / 541 | 369 / 530 |
| serious Total, serious adverse events | 86 / 541 | 85 / 530 |
Outcome results
Primary
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.
Time frame: 0 to 52 weeks
Population: Safety Set - All subjects who were randomized to treatment and took at least one dose of study medication. Subjects were analyzed according to the actual treatment they received for the majority of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Perforomist Inhalation Solution | Kaplan-Meier Probability of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation at 52 Weeks | 15.5 percent |
| Matching Placebo | Kaplan-Meier Probability of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation at 52 Weeks | 14.9 percent |
Primary
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.
Time frame: 0 to 52 weeks
Population: Safety Set - All subjects who were randomized to treatment and took at least one dose of study medication. Subjects were analyzed according to the actual treatment they received for the majority of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Perforomist Inhalation Solution | Number of Subjects With a Primary Event of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation | 64 Participants |
| Matching Placebo | Number of Subjects With a Primary Event of Respiratory Death, First COPD-Related Emergency Room Visit, or First COPD Exacerbation-Related Hospitalisation | 57 Participants |
90% CI: [0.711, 1.308]Regression, Cox
Secondary
FEV1 Changes From Baseline at Months 3, 6, 9 and 12
Time frame: On treatment at months 3, 6, 9 and 12
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization. Only subjects with data collected and valid measurements included
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Perforomist Inhalation Solution | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 3 | 0.058 Litres | Standard Error 0.0116 |
| Perforomist Inhalation Solution | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 6 | 0.057 Litres | Standard Error 0.013 |
| Perforomist Inhalation Solution | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 9 | 0.050 Litres | Standard Error 0.0136 |
| Perforomist Inhalation Solution | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 12 | 0.030 Litres | Standard Error 0.0144 |
| Matching Placebo | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 12 | 0.000 Litres | Standard Error 0.016 |
| Matching Placebo | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 3 | 0.016 Litres | Standard Error 0.0123 |
| Matching Placebo | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 9 | 0.029 Litres | Standard Error 0.0151 |
| Matching Placebo | FEV1 Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FEV1: Month 6 | 0.017 Litres | Standard Error 0.0143 |
Secondary
FVC Changes From Baseline at Months 3, 6, 9 and 12
Time frame: On treatment at months 3, 6, 9 and 12
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization. Only subjects with data collected and valid measurements included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perforomist Inhalation Solution | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 3 | 0.1051 Litres | Standard Deviation 0.40479 |
| Perforomist Inhalation Solution | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 6 | 0.1006 Litres | Standard Deviation 0.38875 |
| Perforomist Inhalation Solution | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 9 | 0.1009 Litres | Standard Deviation 0.39533 |
| Perforomist Inhalation Solution | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 12 | 0.0645 Litres | Standard Deviation 0.4349 |
| Matching Placebo | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 12 | -0.0581 Litres | Standard Deviation 0.38069 |
| Matching Placebo | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 3 | 0.0062 Litres | Standard Deviation 0.38724 |
| Matching Placebo | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 9 | -0.0254 Litres | Standard Deviation 0.40947 |
| Matching Placebo | FVC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline FVC: Month 6 | -0.0241 Litres | Standard Deviation 0.37124 |
Secondary
Health Care Utilization and Economic Impact - Number of Emergency Department Visits
Time frame: 0 to 52 weeks
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Perforomist Inhalation Solution | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | 0 | 447 Participants |
| Perforomist Inhalation Solution | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | 1 | 78 Participants |
| Perforomist Inhalation Solution | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | 2 | 15 Participants |
| Perforomist Inhalation Solution | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | >=3 | 1 Participants |
| Matching Placebo | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | >=3 | 2 Participants |
| Matching Placebo | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | 0 | 437 Participants |
| Matching Placebo | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | 2 | 16 Participants |
| Matching Placebo | Health Care Utilization and Economic Impact - Number of Emergency Department Visits | 1 | 75 Participants |
Secondary
IC Changes From Baseline at Months 3, 6, 9 and 12
Time frame: On treatment at months 3, 6, 9 and 12
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization. Only subjects with data collected and valid measurements included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perforomist Inhalation Solution | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 3 | 0.0287 Litres | Standard Deviation 0.42478 |
| Perforomist Inhalation Solution | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 6 | 0.0440 Litres | Standard Deviation 0.44862 |
| Perforomist Inhalation Solution | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 12 | 0.0477 Litres | Standard Deviation 0.48057 |
| Perforomist Inhalation Solution | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 9 | 0.1584 Litres | Standard Deviation 1.8429 |
| Matching Placebo | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 12 | -0.0105 Litres | Standard Deviation 0.44289 |
| Matching Placebo | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 3 | -0.0119 Litres | Standard Deviation 0.39505 |
| Matching Placebo | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 6 | -0.0106 Litres | Standard Deviation 0.43483 |
| Matching Placebo | IC Changes From Baseline at Months 3, 6, 9 and 12 | Change from Baseline IC: Month 9 | -0.0118 Litres | Standard Deviation 0.43513 |
Secondary
Individual Components of the Primary Composite Endpoint - First COPD-related ER Visit and First COPD Exacerbation-Related Hospitalization
Time frame: 0 to 52 weeks
Population: Safety Set - All subjects who were randomized to treatment and took at least one dose of study medication. Subjects were analyzed according to the actual treatment they received for the majority of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Perforomist Inhalation Solution | Individual Components of the Primary Composite Endpoint - First COPD-related ER Visit and First COPD Exacerbation-Related Hospitalization | Subjects with a COPD- related ER Visit | 46 Participants |
| Perforomist Inhalation Solution | Individual Components of the Primary Composite Endpoint - First COPD-related ER Visit and First COPD Exacerbation-Related Hospitalization | Subjects with a COPD-Related Hospitalization | 39 Participants |
| Matching Placebo | Individual Components of the Primary Composite Endpoint - First COPD-related ER Visit and First COPD Exacerbation-Related Hospitalization | Subjects with a COPD- related ER Visit | 47 Participants |
| Matching Placebo | Individual Components of the Primary Composite Endpoint - First COPD-related ER Visit and First COPD Exacerbation-Related Hospitalization | Subjects with a COPD-Related Hospitalization | 43 Participants |
Secondary
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.
Time frame: 0 to 52 weeks
Population: Safety Set - All subjects who were randomized to treatment and took at least one dose of study medication. Subjects were analyzed according to the actual treatment they received for the majority of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Perforomist Inhalation Solution | Kaplan-Meier Probability of Protocol Defined COPD Exacerbation at 52 Weeks | 34.7 percent |
| Matching Placebo | Kaplan-Meier Probability of Protocol Defined COPD Exacerbation at 52 Weeks | 34.0 percent |
Secondary
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.
Time frame: 0 to 52 weeks
Population: Safety Set - All subjects who were randomized to treatment and took at least one dose of study medication. Subjects were analyzed according to the actual treatment they received for the majority of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Perforomist Inhalation Solution | Number of Subjects With Protocol-Defined COPD Exacerbation | 142 Participants |
| Matching Placebo | Number of Subjects With Protocol-Defined COPD Exacerbation | 135 Participants |
Secondary
Rescue Medication Usage
Number of puffs of rescue medication (albuterol pMDI) used per day
Time frame: 0 to 52 weeks
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perforomist Inhalation Solution | Rescue Medication Usage | Baseline | 2.55 Mean Puffs per Day | Standard Deviation 2.496 |
| Perforomist Inhalation Solution | Rescue Medication Usage | Treatment Phase | 1.92 Mean Puffs per Day | Standard Deviation 2.063 |
| Matching Placebo | Rescue Medication Usage | Baseline | 2.52 Mean Puffs per Day | Standard Deviation 2.484 |
| Matching Placebo | Rescue Medication Usage | Treatment Phase | 2.35 Mean Puffs per Day | Standard Deviation 2.521 |
Secondary
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.
Time frame: On treatment at months 3, 6, 9 and 12
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization. Only subjects with data collected were included
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Perforomist Inhalation Solution | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 3 | -3.252 units on a scale | Standard Error 0.5472 |
| Perforomist Inhalation Solution | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 6 | -2.329 units on a scale | Standard Error 0.6541 |
| Perforomist Inhalation Solution | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 9 | -2.021 units on a scale | Standard Error 0.7022 |
| Perforomist Inhalation Solution | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 12 | -1.453 units on a scale | Standard Error 0.7559 |
| Matching Placebo | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 12 | -1.475 units on a scale | Standard Error 0.8345 |
| Matching Placebo | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 3 | -2.027 units on a scale | Standard Error 0.5727 |
| Matching Placebo | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 9 | -2.115 units on a scale | Standard Error 0.7681 |
| Matching Placebo | Saint Georges Respiratory Questionnaire Scores: Changes From Baseline at Months 3, 6, 9, 12 | Change from Baseline SGRQ Total Score: Month 6 | -2.511 units on a scale | Standard Error 0.7156 |
Secondary
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.
Time frame: 0 to 52 weeks
Population: Safety Set - All subjects who were randomized to treatment and took at least one dose of study medication. Subjects were analyzed according to the actual treatment they received for the majority of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Perforomist Inhalation Solution | Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | Incidence of All Cause Mortalities | 3 Participants |
| Perforomist Inhalation Solution | Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | Incidence of Respiratory Related Mortalities | 0 Participants |
| Perforomist Inhalation Solution | Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | Incidence of COPD Related Mortalities | 0 Participants |
| Matching Placebo | Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | Incidence of All Cause Mortalities | 10 Participants |
| Matching Placebo | Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | Incidence of Respiratory Related Mortalities | 1 Participants |
| Matching Placebo | Summary of All Cause Mortality, COPD Related Mortality and Respiratory Related Mortality | Incidence of COPD Related Mortalities | 1 Participants |
Secondary
Summary of Subjects Requiring Intubation or Non-Invasive Ventilation
Time frame: 0 to 52 weeks
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Perforomist Inhalation Solution | Summary of Subjects Requiring Intubation or Non-Invasive Ventilation | 3 Participants |
| Matching Placebo | Summary of Subjects Requiring Intubation or Non-Invasive Ventilation | 10 Participants |
Secondary
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.
Time frame: On treatment at months 3, 6, 9 and 12
Population: Full Analysis Set: all subjects randomized who took at least one dose of study medication. Subjects were analyzed according to their assigned treatment at randomization.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Perforomist Inhalation Solution | Transition Dyspnea Index | Month 3 | 0.7 units on a scale | Standard Error 0.11 |
| Perforomist Inhalation Solution | Transition Dyspnea Index | Month 6 | 0.5 units on a scale | Standard Error 0.13 |
| Perforomist Inhalation Solution | Transition Dyspnea Index | Month 9 | 0.7 units on a scale | Standard Error 0.14 |
| Perforomist Inhalation Solution | Transition Dyspnea Index | Month 12 | 0.5 units on a scale | Standard Error 0.14 |
| Matching Placebo | Transition Dyspnea Index | Month 12 | 0.6 units on a scale | Standard Error 0.16 |
| Matching Placebo | Transition Dyspnea Index | Month 3 | 0.0 units on a scale | Standard Error 0.12 |
| Matching Placebo | Transition Dyspnea Index | Month 9 | 0.4 units on a scale | Standard Error 0.15 |
| Matching Placebo | Transition Dyspnea Index | Month 6 | 0.4 units on a scale | Standard Error 0.14 |