COPD
Conditions
Keywords
Chronic Obstructive Pulmonary Disease
Brief summary
This is a trial of 12 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer in subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines.
Detailed description
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, efficacy and safety trial of 12 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer in approximately 645 subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines. SUN-101 or placebo will be administered twice daily as an oral inhalation using the investigational eFlow CS nebulizer. Approximately 150 subjects will be enrolled in the substudy (at selected sites only). These subjects will be required to participate in serial spirometry, vital signs, ECGs, and an additional Holter monitor assessment at Visit 6 (Week 12). This subset of subjects will be referred to as the Substudy Population.
Interventions
SUN-101 50 mcg twice daily (BID) eFlow Closed System (CS) nebulizer
SUN-101 25 mcg twice daily (BID) eFlow Closed System (CS) nebulizer
DRUGPlacebo BID eFlow Closed System (CS) nebulizer
Placebo twice daily (BID) eFlow Closed System (CS) nebulizer
Sponsors
Sunovion Respiratory Development Inc.
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. 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, eg, 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 oral, intravenous, or intramuscular 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 QTcF (\> 450 msec for males and \> 470 msec for females) during Screening (Visit 1) as determined from the report provided by the central laboratory, 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 |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 | Baseline and Week 12 | ALL COLLECTED-Spirometry was performed according to internationally accepted standards.Trough FEV1 at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose.Change from baseline in trough FEV1 was calculated as the trough FEV1 value at Week 12 minus the morning trough FEV1 at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose). All collected values were used in this analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random (MAR) ALL COLLECTED and ON TREATMENT data are the same. The only difference is in the number of visits included for those participants who may have discontinued randomized treatment but remained in the study. for all endpoints |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12 | Baseline and Week 12 | ON TEATMENT-Spirometry was performed according to internationally accepted standards.Trough FEV1 at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose.Change from baseline in trough FEV1 was calculated as the trough FEV1 value at Week 12 minus the morning trough FEV1 at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose).Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 | Baseline and Week 12 | ALL COLLECTED Spirometry was performed according to internationally accepted standards. Trough FVC at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random |
| Change From Baseline in Trough Forced Vital Capacity (FVC) Week 12 | Baseline and Week 12 | ON TREATMENT Spirometry was performed according to internationally accepted standards. Trough FVC at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose. Change from baseline in trough FVC was calculated as the trough FVC value at Week 12 minus the morning trough FVC at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose).Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR). |
| Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study | Baseline and Week 12 | ALL COLLECTED Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: symptoms, activity, and impacts. A score was calculated for each of these 3 subscales and a Total score was calculated. In each case the lowest possible value is 0 and the highest 100. Higher values correspond to greater impairment of health status. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not. Values not collected remained as missing values and were assumed to be missing at random (MAR). |
| Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study | Baseline and Week 12 | ON TREATMENT Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: symptoms, activity, and impacts. A score was calculated for each of these 3 subscales and a Total score was calculated. In each case the lowest possible value is 0 and the highest 100. Higher values correspond to greater impairment of health status. Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR). |
| Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period | Week 0-12 | ALL COLLECTED Participants completed an electronic diary (eDiary) daily (night time) to record the number of puffs of rescue medication inhaled in the previous 24 hours. A negative change from baseline indicates improvement. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not. Values not collected remained as missing values and were assumed to be missing at random (MAR). |
| Number of Subjects With Major Adverse Cardiac Events (MACE) | Week 0-12 | ALL COLLECTED 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 for the double-blind period (from the first date of study medication until the date of last contact) |
| Percentage of Subjects With Major Cardiac Events (MACE) | Week 0-12 | ALL COLLECTED 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 for the double-blind period (from the first date of study medication until the date of last contact) |
| Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population | Baseline and Week 12 | ALL COLLECTED The standardized FEV1 AUC(0-12) was calculated at weeks 0 and 12 for the Substudy Population with extended spirometry measurements. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time. Intermittent missing spirometry measurements were ignored and the trapezoidal rule would simply span the missing time point(s). If the Hour 12 time point was missing, then the AUC(0-12) calculation was based on the time interval up to the last non-missing time point prior to Hour 12. If a subject has a missing baseline FEV1, then that subject had a missing AUC. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random (MAR). |
| Percent of Subjects With Treatment Emergent Adverse Events (TEAE) | Week 0-12 | ON TREATMENT A TEAE is defined as any non-serious AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE. |
| Number of Subjects With Treatment Emergent Serious Adverse Events (SAE) | Week 0-12 | ON TREATMENT A treatment emergent SAE is defined as any SAE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent SAE is an on-treatment SAE |
| Percent of Subjects With Treatment Emergent Serious Adverse Events (SAE) | Week 0-12 | ON TREATMENT A treatment emergent SAE is defined as any SAE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent SAE is an on-treatment SAE |
| Number of Subjects Who Discontinue Treatment Due to TEAE | Week 0-12 | ON TREATMENT A TEAE is defined as any AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE. |
| Percent of Subjects Who Discontinue Treatment Due to TEAE | Week 0-12 | ON TREATMENT A TEAE is defined as any AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE. |
| Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | Week 0-12 | ALL COLLECTED 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 for the double-blind period (from the first date of study medication until the date of last contact)I ncidence 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. |
| Number of Subjects With Treatment Emergent Adverse Events (TEAE) | Week 0-12 | ON TREATMENT A TEAE is defined as any non-serious AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE. |
| Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population | Baseline and Week 12 | ON TREATMENT The standardized FEV1 AUC(0-12) was calculated at weeks 0 and 12 for the Substudy Population with extended spirometry measurements. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time. Intermittent missing spirometry measurements were ignored and the trapezoidal rule would simply span the missing time points. If the Hour 12 time point was missing, then the AUC(0-12) calculation was based on the time interval up to the last non-missing time point prior to Hour 12. If a subject has a missing baseline FEV1, then that subject had a missing AUC.Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer SUN-101 50 mcg twice daily (BID) eFlow (R) Closed System (CR) nebulizer
SUN-101 50 mcg BID eFlow (CS) nebulizer: SUN-101 50 mcg twice daily (BID) eFlow Closed System (CS) nebulizer | 218 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer SUN-101 25 mcg twice daily (BID) eFlow (R) Closed System (CR) nebulizer
SUN-101 25 mcg BID eFlow (CS) nebulizer: SUN-101 25 mcg twice daily (BID) eFlow Closed System (CS) nebulizer | 217 |
| Placebo BID eFlow (CS) Nebulizer Placebo twice daily (BID) eFlow (R) Closed System (CR) nebulizer
Placebo BID eFlow Closed System (CS) nebulizer: Placebo twice daily (BID) eFlow Closed System (CS) nebulizer | 218 |
| Total | 653 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| All Collected | Death | 1 | 0 | 0 |
| All Collected | exacerbation of COPD | 0 | 0 | 1 |
| All Collected | instillation site pain | 0 | 0 | 1 |
| All Collected | invetigator disretion | 2 | 0 | 0 |
| All Collected | Lost to Follow-up | 3 | 2 | 3 |
| All Collected | moved/travel | 0 | 1 | 0 |
| All Collected | Withdrawal by Subject | 11 | 11 | 22 |
| On Study Treatment | Adverse Event | 10 | 8 | 20 |
| On Study Treatment | dissastisfaction with device | 2 | 1 | 4 |
| On Study Treatment | durg not working | 0 | 1 | 1 |
| On Study Treatment | investigator discretion | 2 | 0 | 0 |
| On Study Treatment | Lack of Efficacy | 2 | 3 | 4 |
| On Study Treatment | Lost to Follow-up | 2 | 1 | 1 |
| On Study Treatment | move/travel | 2 | 6 | 5 |
| On Study Treatment | non-compliance with study medication | 0 | 0 | 2 |
| On Study Treatment | Withdrawal by Subject | 7 | 3 | 5 |
Baseline characteristics
| Characteristic | SUN-101 25 mcg BID eFlow (CS) Nebulizer | Total | SUN-101 50 mcg BID eFlow (CS) Nebulizer | Placebo BID eFlow (CS) Nebulizer |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 95 Participants | 287 Participants | 83 Participants | 109 Participants |
| Age, Categorical Between 18 and 65 years | 122 Participants | 366 Participants | 135 Participants | 109 Participants |
| Age, Continuous | 63.1 years STANDARD_DEVIATION 8.78 | 63.1 years STANDARD_DEVIATION 8.42 | 62.5 years STANDARD_DEVIATION 8.09 | 63.7 years STANDARD_DEVIATION 8.37 |
| background long-acting beta(2) agonist (LABA) use background LABA use =no | 151 Participants | 456 Participants | 150 Participants | 155 Participants |
| background long-acting beta(2) agonist (LABA) use background LABA use =yes | 66 Participants | 197 Participants | 68 Participants | 63 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk cerebrovascular disease | 13 Participants | 37 Participants | 10 Participants | 14 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk clinically significant arrhythmia | 13 Participants | 22 Participants | 7 Participants | 2 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk heart failure | 7 Participants | 24 Participants | 9 Participants | 8 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk high cardiovascular risk | 139 Participants | 422 Participants | 141 Participants | 142 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk hyertension | 128 Participants | 393 Participants | 127 Participants | 138 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk low cardiovascular risk | 78 Participants | 231 Participants | 77 Participants | 76 Participants |
| cardiovascular risk (low/high) and categories for high caridovascular risk peripheral arterial disease | 13 Participants | 37 Participants | 10 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 19 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 210 Participants | 634 Participants | 212 Participants | 212 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced expiratory volume in one second (FEV1) | 1.3108 liters STANDARD_DEVIATION 0.50243 | 1.3325 liters STANDARD_DEVIATION 0.50297 | 1.3745 liters STANDARD_DEVIATION 0.52957 | 1.3122 liters STANDARD_DEVIATION 0.47511 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 53 Participants | 18 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 200 Participants | 594 Participants | 198 Participants | 196 Participants |
| Region of Enrollment United States | 217 Participants | 653 Participants | 218 Participants | 218 Participants |
| Sex: Female, Male Female | 99 Participants | 304 Participants | 98 Participants | 107 Participants |
| Sex: Female, Male Male | 118 Participants | 349 Participants | 120 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 218 | 23 / 217 | 38 / 218 |
| serious Total, serious adverse events | 10 / 218 | 8 / 217 | 11 / 218 |
Outcome results
Primary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
ALL COLLECTED-Spirometry was performed according to internationally accepted standards.Trough FEV1 at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose.Change from baseline in trough FEV1 was calculated as the trough FEV1 value at Week 12 minus the morning trough FEV1 at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose). All collected values were used in this analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random (MAR) ALL COLLECTED and ON TREATMENT data are the same. The only difference is in the number of visits included for those participants who may have discontinued randomized treatment but remained in the study. for all endpoints
Time frame: Baseline and Week 12
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 | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 | 0.0961 liters | Standard Error 0.01371 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 | 0.0886 liters | Standard Error 0.01369 |
| Placebo BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 | -0.0075 liters | Standard Error 0.01397 |
Comparison: The change from baseline in trough FEV1 was analyzed using a mixed model for repeated measures including terms for treatment, cardiovascular risk, background LABA use, visit, visit by treatment interaction, and baseline FEV1 as a covariate. An unstructured covariance matrix was used.p-value: <0.000195% CI: [0.0663, 0.1409]MMixed Model Repeat Measurement
Comparison: The change from baseline in trough FEV1 was analyzed using a mixed model for repeated measures including terms for treatment, cardiovascular risk, background LABA use, visit, visit by treatment interaction, and baseline FEV1 as a covariate. An unstructured covariance matrix was used.p-value: <0.000195% CI: [0.0589, 0.1334]Mixed Model Repeat Measurement
Primary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12
ON TEATMENT-Spirometry was performed according to internationally accepted standards.Trough FEV1 at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose.Change from baseline in trough FEV1 was calculated as the trough FEV1 value at Week 12 minus the morning trough FEV1 at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose).Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Baseline and Week 12
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 | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12 | 0.1025 liters | Standard Error 0.01497 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12 | 0.0814 liters | Standard Error 0.01475 |
| Placebo BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12 | -0.0238 liters | Standard Error 0.01534 |
Comparison: The change from baseline in trough FEV1 was analyzed using mixed model repeated measures including terms for treatment, cardiovascular risk, background LABA use, visit week, visit week by treatment interaction, and baseline FEV1 as a covariate. An unstructured covariance matrix was used.p-value: <0.000195% CI: [0.0856, 0.1672]Least squares mean (SE)
Comparison: The change from baseline in trough FEV1 was analyzed using mixed model repeated measures including terms for treatment, cardiovascular risk, background LABA use, visit week, visit week by treatment interaction, and baseline FEV1 as a covariate. An unstructured covariance matrix was used.p-value: <0.000195% CI: [0.0647, 0.1457]LS mean (SE)
Secondary
Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study
ALL COLLECTED Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: symptoms, activity, and impacts. A score was calculated for each of these 3 subscales and a Total score was calculated. In each case the lowest possible value is 0 and the highest 100. Higher values correspond to greater impairment of health status. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not. Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Baseline and Week 12
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 | Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study | -2.363 scores on a scale | Standard Error 0.8344 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study | -4.250 scores on a scale | Standard Error 0.8211 |
| Placebo BID eFlow (CS) Nebulizer | Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study | -0.844 scores on a scale | Standard Error 0.8396 |
Secondary
Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study
ON TREATMENT Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: symptoms, activity, and impacts. A score was calculated for each of these 3 subscales and a Total score was calculated. In each case the lowest possible value is 0 and the highest 100. Higher values correspond to greater impairment of health status. Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Baseline and Week 12
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 | Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study | -2.538 scores on a scale | Standard Error 0.8391 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study | -3.762 scores on a scale | Standard Error 0.8187 |
| Placebo BID eFlow (CS) Nebulizer | Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study | -0.690 scores on a scale | Standard Error 0.8535 |
Secondary
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12
ALL COLLECTED Spirometry was performed according to internationally accepted standards. Trough FVC at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random
Time frame: Baseline and Week 12
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 | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 | 0.1476 liters | Standard Error 0.02226 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 | 0.1515 liters | Standard Error 0.0222 |
| Placebo BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 | 0.0147 liters | Standard Error 0.2266 |
Secondary
Change From Baseline in Trough Forced Vital Capacity (FVC) Week 12
ON TREATMENT Spirometry was performed according to internationally accepted standards. Trough FVC at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose. Change from baseline in trough FVC was calculated as the trough FVC value at Week 12 minus the morning trough FVC at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose).Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Baseline and Week 12
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 | Change From Baseline in Trough Forced Vital Capacity (FVC) Week 12 | 0.1566 liters | Standard Error 0.02392 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Vital Capacity (FVC) Week 12 | 0.1393 liters | Standard Error 0.02353 |
| Placebo BID eFlow (CS) Nebulizer | Change From Baseline in Trough Forced Vital Capacity (FVC) Week 12 | -0.0101 liters | Standard Error 0.245 |
Secondary
Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period
ALL COLLECTED Participants completed an electronic diary (eDiary) daily (night time) to record the number of puffs of rescue medication inhaled in the previous 24 hours. A negative change from baseline indicates improvement. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not. Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Week 0-12
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 | Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period | -0.815 puffs (medication used) | Standard Error 0.1234 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period | -0.609 puffs (medication used) | Standard Error 0.1259 |
| Placebo BID eFlow (CS) Nebulizer | Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period | -0.632 puffs (medication used) | Standard Error 0.1257 |
Secondary
Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE)
ALL COLLECTED 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 for the double-blind period (from the first date of study medication until the date of last contact)I ncidence 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.
Time frame: Week 0-12
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 | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | MACE score | 45.5 events per 100 person-years |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | Cardiovascular Death | 15.2 events per 100 person-years |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | non-fatal myocardial infraction | 15.2 events per 100 person-years |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | non-fatal stroke | 15.2 events per 100 person-years |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | non-fatal stroke | 0 events per 100 person-years |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | MACE score | 0 events per 100 person-years |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | non-fatal myocardial infraction | 0 events per 100 person-years |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | Cardiovascular Death | 0 events per 100 person-years |
| Placebo BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | non-fatal stroke | 0 events per 100 person-years |
| Placebo BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | Cardiovascular Death | 0 events per 100 person-years |
| Placebo BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | non-fatal myocardial infraction | 0 events per 100 person-years |
| Placebo BID eFlow (CS) Nebulizer | Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE) | MACE score | 0 events per 100 person-years |
Secondary
Number of Subjects Who Discontinue Treatment Due to TEAE
ON TREATMENT A TEAE is defined as any AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE.
Time frame: Week 0-12
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study meidcation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects Who Discontinue Treatment Due to TEAE | 8 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects Who Discontinue Treatment Due to TEAE | 7 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects Who Discontinue Treatment Due to TEAE | 21 participants |
Secondary
Number of Subjects With Major Adverse Cardiac Events (MACE)
ALL COLLECTED 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 for the double-blind period (from the first date of study medication until the date of last contact)
Time frame: Week 0-12
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) | MACE score | 3 participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | Cardiovascular Death | 1 participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | non-fatal myocardial infraction | 1 participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | non-fatal stroke | 1 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | non-fatal stroke | 0 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | MACE score | 0 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | non-fatal myocardial infraction | 0 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | Cardiovascular Death | 0 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | non-fatal stroke | 0 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | Cardiovascular Death | 0 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | non-fatal myocardial infraction | 0 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects With Major Adverse Cardiac Events (MACE) | MACE score | 0 participants |
Secondary
Number of Subjects With Treatment Emergent Adverse Events (TEAE)
ON TREATMENT A TEAE is defined as any non-serious AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE.
Time frame: Week 0-12
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) | 105 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Treatment Emergent Adverse Events (TEAE) | 86 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects With Treatment Emergent Adverse Events (TEAE) | 114 participants |
Secondary
Number of Subjects With Treatment Emergent Serious Adverse Events (SAE)
ON TREATMENT A treatment emergent SAE is defined as any SAE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent SAE is an on-treatment SAE
Time frame: Week 0-12
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) | 10 participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Number of Subjects With Treatment Emergent Serious Adverse Events (SAE) | 8 participants |
| Placebo BID eFlow (CS) Nebulizer | Number of Subjects With Treatment Emergent Serious Adverse Events (SAE) | 11 participants |
Secondary
Percentage of Subjects With Major Cardiac Events (MACE)
ALL COLLECTED 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 for the double-blind period (from the first date of study medication until the date of last contact)
Time frame: Week 0-12
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 Cardiac Events (MACE) | MACE score | 1.4 percentage of participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | Cardiovascular Death | 0.5 percentage of participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | non-fatal myocardial infraction | 0.5 percentage of participants |
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | non-fatal stroke | 0.5 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | non-fatal stroke | 0 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | MACE score | 0 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | non-fatal myocardial infraction | 0 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | Cardiovascular Death | 0 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | non-fatal stroke | 0 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | Cardiovascular Death | 0 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | non-fatal myocardial infraction | 0 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percentage of Subjects With Major Cardiac Events (MACE) | MACE score | 0 percentage of participants |
Secondary
Percent of Subjects Who Discontinue Treatment Due to TEAE
ON TREATMENT A TEAE is defined as any AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE.
Time frame: Week 0-12
Population: Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study meidcation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Percent of Subjects Who Discontinue Treatment Due to TEAE | 3.7 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percent of Subjects Who Discontinue Treatment Due to TEAE | 3.2 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percent of Subjects Who Discontinue Treatment Due to TEAE | 9.6 percentage of participants |
Secondary
Percent of Subjects With Treatment Emergent Adverse Events (TEAE)
ON TREATMENT A TEAE is defined as any non-serious AE that occurred on or after the first dose of study medication and within 7 days after the last dose of study medication, or any serious AE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent AE is an on-treatment AE.
Time frame: Week 0-12
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 | Percent of Subjects With Treatment Emergent Adverse Events (TEAE) | 48.2 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percent of Subjects With Treatment Emergent Adverse Events (TEAE) | 39.6 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percent of Subjects With Treatment Emergent Adverse Events (TEAE) | 52.3 percentage of participants |
Secondary
Percent of Subjects With Treatment Emergent Serious Adverse Events (SAE)
ON TREATMENT A treatment emergent SAE is defined as any SAE that occurred on or after the first dose of study medication and within 30 days after the last dose of study medication. A treatment emergent SAE is an on-treatment SAE
Time frame: Week 0-12
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 | Percent of Subjects With Treatment Emergent Serious Adverse Events (SAE) | 4.6 percentage of participants |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Percent of Subjects With Treatment Emergent Serious Adverse Events (SAE) | 3.7 percentage of participants |
| Placebo BID eFlow (CS) Nebulizer | Percent of Subjects With Treatment Emergent Serious Adverse Events (SAE) | 5.0 percentage of participants |
Secondary
Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population
ON TREATMENT The standardized FEV1 AUC(0-12) was calculated at weeks 0 and 12 for the Substudy Population with extended spirometry measurements. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time. Intermittent missing spirometry measurements were ignored and the trapezoidal rule would simply span the missing time points. If the Hour 12 time point was missing, then the AUC(0-12) calculation was based on the time interval up to the last non-missing time point prior to Hour 12. If a subject has a missing baseline FEV1, then that subject had a missing AUC.Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Baseline and Week 12
Population: The Substudy Population consisted of all ITT subjects who participated in post-dose serial measurements, including serial spirometry, serial ECGs, serial vital sign measurements, as well as Holter monitoring at Visit 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population | 0.0708 liters | Standard Error 0.02792 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population | 0.0496 liters | Standard Error 0.0328 |
| Placebo BID eFlow (CS) Nebulizer | Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population | -0.0527 liters | Standard Error 0.0345 |
Secondary
Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population
ALL COLLECTED The standardized FEV1 AUC(0-12) was calculated at weeks 0 and 12 for the Substudy Population with extended spirometry measurements. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time. Intermittent missing spirometry measurements were ignored and the trapezoidal rule would simply span the missing time point(s). If the Hour 12 time point was missing, then the AUC(0-12) calculation was based on the time interval up to the last non-missing time point prior to Hour 12. If a subject has a missing baseline FEV1, then that subject had a missing AUC. All collected values were used in the analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random (MAR).
Time frame: Baseline and Week 12
Population: The Substudy Population consisted of all ITT subjects who participated in post-dose serial measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SUN-101 50 mcg BID eFlow (CS) Nebulizer | Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population | 0.0749 liters | Standard Error 0.02638 |
| SUN-101 25 mcg BID eFlow (CS) Nebulizer | Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population | 0.0579 liters | Standard Error 0.3011 |
| Placebo BID eFlow (CS) Nebulizer | Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population | -0.0474 liters | Standard Error 0.03229 |