Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD
- Conditions
- COPD
- Interventions
- Drug: Placebo BID eFlow Closed System (CS) nebulizer
- Registration Number
- NCT02347761
- Lead Sponsor
- Sunovion Respiratory Development Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 653
- Male or female patients age ≥ 40 years, inclusive
- A clinical diagnosis of COPD according to the GOLD 2014 guidelines
- Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent)
- Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 < 80% of predicted normal and > 0.7 L during Screening (Visit 1)
- Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio < 0.70 during Screening (Visit 1)
- Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005)
- 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
- Willing and able to provide written informed consent
- Willing and able to attend all study visits and adhere to all study assessments and procedures
- 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
- Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis or other non-specific pulmonary disease).
- Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening (Visit 1)
- Use of daily oxygen therapy > 12 hours per day
- Respiratory tract infection within 6 weeks prior to Screening (Visit 1)
- Use of oral, intravenous, or intramuscular steroids within 3 months prior to Screening (Visit 1)
- 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
- 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
- History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months.
- History of narrow angle glaucoma
- History of hypersensitivity or intolerance to aerosol medications
- Recent documented history (within the previous 3 months) of substance abuse
- Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator
- 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
- Previously received SUN-101 (active treatment; formerly known as EP-101).
- Contraindicated for treatment with, or having a history of reactions/hypersensitivity to anticholinergic agents, beta2 agonists, or sympathomimetic amines
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo BID eFlow (CS) nebulizer Placebo BID eFlow Closed System (CS) nebulizer Placebo twice daily (BID) eFlow (R) Closed System (CR) nebulizer SUN-101 50 mcg BID eFlow (CS) nebulizer SUN-101 50 mcg BID eFlow (CS) nebulizer SUN-101 50 mcg twice daily (BID) eFlow (R) Closed System (CR) nebulizer SUN-101 25 mcg BID eFlow (CS) nebulizer SUN-101 25 mcg BID eFlow (CS) nebulizer SUN-101 25 mcg twice daily (BID) eFlow (R) Closed System (CR) nebulizer
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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).
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).
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 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).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 randomNumber 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.
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.
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)
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).
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).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)
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 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
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.
Trial Locations
- Locations (43)
Minnesota Lung Center
🇺🇸Woodbury, Minnesota, United States
AppleMed Research, Inc.
🇺🇸Miami, Florida, United States
Clinical Trials of Florida, LLC
🇺🇸Miami, Florida, United States
Columbus Regional Research Institute
🇺🇸Columbus, Ohio, United States
Research Protocol Management Specialists
🇺🇸Pittsburgh, Pennsylvania, United States
Palmetto Medical Research Associates, LLC
🇺🇸Easley, South Carolina, United States
Pioneer Research Solutions, Inc.
🇺🇸Houston, Texas, United States
Columbus Clinical Research, Inc
🇺🇸Columbus, Ohio, United States
Clinical Research Consortium - Arizona
🇺🇸Tempe, Arizona, United States
Clinical Research of West Florida, Inc
🇺🇸Tampa, Florida, United States
Pinnacle Research Group, LLC
🇺🇸Anniston, Alabama, United States
Midwest Chest Consultants, P.C.
🇺🇸Saint Charles, Missouri, United States
Clinical Research Institute of Southern Oregon, PC
🇺🇸Medford, Oregon, United States
Optimed Research, LTD
🇺🇸Columbus, Ohio, United States
Spartanburg Medical Research
🇺🇸Spartanburg, South Carolina, United States
Pulmonary Associates, PA
🇺🇸Phoenix, Arizona, United States
Clinical Research Consortium
🇺🇸Las Vegas, Nevada, United States
Florida Institute for Clinical Research, LLC
🇺🇸Orlando, Florida, United States
Clermont Medical Research
🇺🇸Clermont, Florida, United States
Riverside Clinical Research
🇺🇸Edgewater, Florida, United States
Desert Sun Clinical Research, LLC
🇺🇸Tucson, Arizona, United States
Western States Clinical Research, Inc.
🇺🇸Wheat Ridge, Colorado, United States
Clinical Research of West Florida, Inc.
🇺🇸Clearwater, Florida, United States
Pulmonary Disease Specialists, PA, d/b/a PDS Research
🇺🇸Kissimmee, Florida, United States
Emerald Coast Research Associates
🇺🇸Panama City, Florida, United States
Pulmonary Research Institute of Southeast Michigan
🇺🇸Livonia, Michigan, United States
Abraham Reasearch, PLLC
🇺🇸Fort Mitchell, Kentucky, United States
AAIR Research Center
🇺🇸Rochester, New York, United States
American Health Research, Inc.
🇺🇸Charlotte, North Carolina, United States
PMG Research of Wilmington
🇺🇸Wilmington, North Carolina, United States
Hickory Research Center
🇺🇸Hickory, North Carolina, United States
North Carolina Clinical Research
🇺🇸Raleigh, North Carolina, United States
Safe Harbor Clinical Research
🇺🇸East Providence, Rhode Island, United States
Greenville Pharmaceutical Research, Inc
🇺🇸Greenville, South Carolina, United States
Upstate Pharmaceutical Research
🇺🇸Greenville, South Carolina, United States
CU Pharmaceutical Research
🇺🇸Union, South Carolina, United States
S. Carolina Pharmaceutical Research
🇺🇸Spartanburg, South Carolina, United States
Piedmont Research Partners, LLC
🇺🇸Indian Land, South Carolina, United States
Texas Pulmonary and Critical Care Consultants, PA
🇺🇸Fort Worth, Texas, United States
Sylvana Research Associates
🇺🇸San Antonio, Texas, United States
Pulmonary Research of Abingdon, LLC
🇺🇸Abingdon, Virginia, United States
Central Texas Health Research
🇺🇸New Braunfels, Texas, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸Richmond, Virginia, United States