Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD
Brief summary
This is a long-term safety trial of 48 weeks. Eligible subjects will enter the 48-week, open-label treatment period to receive one of two treatments (SUN-101 given as 50 mcg twice a day or Spiriva® \[tiotropium\] given as 18 mcg once a day).
Detailed description
This is a Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter, long-term safety trial of 48 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer or Spiriva in approximately 1050 subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines. Eligible subjects will enter the 48-week, open-label treatment period following randomization to receive one of two treatments (SUN-101 given as 50 mcg BID or Spiriva® \[tiotropium\] given as 18 mcg QD). The hypothesis for this study is that the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subjects randomized to SUN-101 is numerically similar to the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subject randomized to Spiriva (tiotropium).
Interventions
SUN-101 (Glycopyrrolate) 50 mcg twice daily (BID) via eFlow Closed System (CS) nebulizer
DRUGSpiriva® 18 mcg QD Handihaler
Spiriva (tiotropium) 18 mcg once daily (QD) via Handihaler
Sponsors
Sunovion Respiratory Development Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients age ≥ 40 years, inclusive. 2. A clinical diagnosis of COPD according to the GOLD 2014 guidelines. 3. Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent). 4. Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 \< 80% of predicted normal and \> 0.7 L during Screening (Visit 1). 5. Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio \< 0.70 during Screening (Visit 1). 6. Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005). 7. Subject, if female ≤ 65 years of age and of child bearing potential, must have a negative serum pregnancy test at Visit 1. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control: a) an oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 1 month prior to entering the study with continued use throughout the study and for thirty days following participation; b) barrier method of contraception, e.g., condom and /or diaphragm with spermicide while participating in the study; and/or c) abstinence.. 8. Willing and able to provide written informed consent. 9. Willing and able to attend all study visits and adhere to all study assessments and procedures.
Exclusion criteria
1. Severe comorbidities including unstable cardiac or pulmonary disease or any other medical conditions that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject. 2. Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis or other non-specific pulmonary disease). 3. Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening (Visit 1). 4. Use of daily oxygen therapy \> 12 hours per day. 5. Respiratory tract infection within 6 weeks prior to Screening (Visit 1). 6. Use of systemic steroids within 3 months prior to Screening (Visit 1). 7. History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localized basal cell carcinoma of the skin. 8. Prolonged QTc (\> 450 msec for males and \> 470 msec for females) during Screening (Visit 1), or history of long QT syndrome. 9. History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months. 10. History of narrow angle glaucoma. 11. History of hypersensitivity or intolerance to aerosol medications. 12. Recent documented history (within the previous 3 months) of substance abuse. 13. Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator. 14. Participation in another investigational drug study where drug was received within 30 days prior to Screening (Visit 1) or current participation in another investigational drug trial, including a SUN-101 study. 15. Previously received SUN-101 (active treatment; formerly known as EP-101). 16. Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, beta2 agonists, or sympathomimetic amines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Discontinue the Study Due to TEAE | Up to 48 Weeks | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. |
| Percentage of Subjects With Treatment-emergent Adverse Events | Up to Week 48 | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. |
| Number of Subjects With Treatment-emergent Serious Adverse Events (SAE) | Up to Week 48 | A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date. |
| Percentage of Subjects With Treatment-emergent Serious Adverse | Up to Week 48 | A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date. |
| Number of Subjects Who Discontinue the Study Due to TEAE | Up to Week 48 | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. |
| Number of Subjects With Treatment-emergent Adverse Events (TEAE) | Up to Week 48 | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | Up to 48 Weeks | All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact. |
| Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | up to week 48 | All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact. |
| Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects | Up to Week 48 | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the FEV1 values collected at the end of the dosing interval at each clinic visit. The mean change from baseline in trough FEV1 over the 48 week treatment period is calculated by averaging the trough FEV1 changes from baseline across all study visits while subjects are taking randomized treatment. Values affected by other medication use were to be set to missing. |
| Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | Up to Week 48 | All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact. |
Countries
Czechia, Hungary, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer SUN-101 (Glycopyrrolate) 50 mcg twice daily (BID) via eFlow Closed System (CS) nebulizer
SUN-101 50 mcg BID eFlow (CS) nebulizer: SUN-101 (Glycopyrrolate) 50 mcg twice daily (BID) via eFlow Closed System (CS) nebulizer | 620 |
| Spiriva 18 mcg QD Handihaler Spiriva (tiotropium) 18 mcg once daily (QD) via Handihaler
Spiriva® 18 mcg QD Handihaler: Spiriva (tiotropium) 18 mcg once daily (QD) via Handihaler | 466 |
| Total | 1,086 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 62 | 11 |
| Overall Study | Death | 3 | 4 |
| Overall Study | Lack of Efficacy | 13 | 3 |
| Overall Study | Lost to Follow-up | 15 | 5 |
| Overall Study | non compliance with study medication | 6 | 2 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | sheduling conflict | 1 | 0 |
| Overall Study | sponsor decision | 0 | 3 |
| Overall Study | subject withdrew after randomization | 1 | 0 |
| Overall Study | Withdrawal by Subject | 79 | 33 |
Baseline characteristics
| Characteristic | SUN-101 50 mcg BID eFlow (CS) Nebulizer | Spiriva 18 mcg QD Handihaler | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 290 Participants | 210 Participants | 500 Participants |
| Age, Categorical Between 18 and 65 years | 330 Participants | 256 Participants | 586 Participants |
| Age, Continuous | 63.3 years STANDARD_DEVIATION 8.46 | 63.3 years STANDARD_DEVIATION 8.97 | 63.3 years STANDARD_DEVIATION 8.68 |
| background long-acting beta (2) agonist (LABA) use background LABA use -no | 353 Participants | 274 Participants | 627 Participants |
| background long-acting beta (2) agonist (LABA) use background LABA use -yes | 267 Participants | 192 Participants | 459 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk cerebrovascular disease | 28 Participants | 18 Participants | 46 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk clinically significant arrhythmia | 22 Participants | 14 Participants | 36 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk heart failure | 23 Participants | 9 Participants | 32 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk high cardiovascular risk | 401 Participants | 297 Participants | 698 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk hyertension | 362 Participants | 275 Participants | 637 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk ischemic heart disease | 61 Participants | 44 Participants | 105 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk low cardiovascular risk | 219 Participants | 169 Participants | 388 Participants |
| cardiovascular risk (low/high) and categories for high cardiovascular risk periheral arterial disease | 39 Participants | 24 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 611 Participants | 457 Participants | 1068 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Forced expiratory volume in one second (FEV1) | 1.3399 liters STANDARD_DEVIATION 0.49604 | 1.3257 liters STANDARD_DEVIATION 0.50186 | 1.3365 liters STANDARD_DEVIATION 0.51414 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 27 Participants | 62 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 582 Participants | 436 Participants | 1018 Participants |
| Region of Enrollment Czechia | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Hungary | 34 Participants | 20 Participants | 54 Participants |
| Region of Enrollment Russia | 25 Participants | 21 Participants | 46 Participants |
| Region of Enrollment United States | 556 Participants | 421 Participants | 977 Participants |
| Sex: Female, Male Female | 270 Participants | 206 Participants | 476 Participants |
| Sex: Female, Male Male | 350 Participants | 260 Participants | 610 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 620 | 4 / 466 |
| other Total, other adverse events | 195 / 620 | 133 / 466 |
| serious Total, serious adverse events | 76 / 620 | 49 / 466 |
Outcome results
Primary
Number of Subjects Who Discontinue the Study Due to TEAE
A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.
Time frame: Up to Week 48
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects Who Discontinue the Study Due to TEAE | 62 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects Who Discontinue the Study Due to TEAE | 13 participants |
Primary
Number of Subjects With Treatment-emergent Adverse Events (TEAE)
A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.
Time frame: Up to Week 48
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Treatment-emergent Adverse Events (TEAE) | 430 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects With Treatment-emergent Adverse Events (TEAE) | 312 participants |
Primary
Number of Subjects With Treatment-emergent Serious Adverse Events (SAE)
A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date.
Time frame: Up to Week 48
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Treatment-emergent Serious Adverse Events (SAE) | 76 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects With Treatment-emergent Serious Adverse Events (SAE) | 49 participants |
Primary
Percentage of Subjects Who Discontinue the Study Due to TEAE
A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.
Time frame: Up to 48 Weeks
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects Who Discontinue the Study Due to TEAE | 10.0 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects Who Discontinue the Study Due to TEAE | 2.8 percentage of participants |
Primary
Percentage of Subjects With Treatment-emergent Adverse Events
A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.
Time frame: Up to Week 48
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Treatment-emergent Adverse Events | 69.4 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects With Treatment-emergent Adverse Events | 67.0 percentage of participants |
Primary
Percentage of Subjects With Treatment-emergent Serious Adverse
A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date.
Time frame: Up to Week 48
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Treatment-emergent Serious Adverse | 12.3 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects With Treatment-emergent Serious Adverse | 10.5 percentage of participants |
Secondary
Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke
All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact.
Time frame: up to week 48
Population: Incidence rate: TT= Total Time in years. Total Time (TT) is defined as the time from the first date of study drug until the latter of the date of last contact or 30 days after the date of last dose. Incidence Rate (per 1000 person-years) = n/TT x 1000.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | MACE score | 6.4 event per 1000 person years |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | cardiovascular death | 2.1 event per 1000 person years |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal myocardial infarction | 4.3 event per 1000 person years |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal stroke | 0 event per 1000 person years |
| Spiriva 18 mcg QD Handihaler | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal stroke | 2.5 event per 1000 person years |
| Spiriva 18 mcg QD Handihaler | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | MACE score | 20.3 event per 1000 person years |
| Spiriva 18 mcg QD Handihaler | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal myocardial infarction | 12.7 event per 1000 person years |
| Spiriva 18 mcg QD Handihaler | Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | cardiovascular death | 5.1 event per 1000 person years |
Secondary
Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the FEV1 values collected at the end of the dosing interval at each clinic visit. The mean change from baseline in trough FEV1 over the 48 week treatment period is calculated by averaging the trough FEV1 changes from baseline across all study visits while subjects are taking randomized treatment. Values affected by other medication use were to be set to missing.
Time frame: Up to Week 48
Population: Intent to Treat (ITT) Population: all subjects who were randomized to treatment and received at least one dose of study medication. Subjects were analyzed based on the treatment they were randomized to.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects | 0.1016 liters | Standard Error 0.00698 |
| Spiriva 18 mcg QD Handihaler | Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects | 0.0931 liters | Standard Error 0.00779 |
p-value: 0.404195% CI: [-0.0114, 0.0283]ANCOVA
Secondary
Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke
All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact.
Time frame: Up to Week 48
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | MACE score | 3 participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal myocardial infarction | 2 participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal stroke | 0 participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | cardiovascular death | 1 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal stroke | 1 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | MACE score | 8 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | cardiovascular death | 2 participants |
| Spiriva 18 mcg QD Handihaler | Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal myocardial infarction | 5 participants |
Secondary
Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke
All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact.
Time frame: Up to 48 Weeks
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | MACE score | 0.5 percentage of participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | cardiovascular death | 0.2 percentage of participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal myocardial infarction | 0.3 percentage of participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal stroke | 0 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal stroke | 0.2 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | MACE score | 1.7 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | non-fatal myocardial infarction | 1.1 percentage of participants |
| Spiriva 18 mcg QD Handihaler | Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | cardiovascular death | 0.4 percentage of participants |