Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD (GOLDEN-4)

Chronic Obstructive Pulmonary Disease Clinical Trial

— GOLDEN-4  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD: GOLDEN-4 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02347774
• Other study ID #: SUN101-302
• Status: Completed
• Phase: Phase 3
• First received: January 21, 2015
• Last updated: February 13, 2018
• Start date: February 2015
• Est. completion date: December 2015

Study information

• Verified date: February 2018
• Source: Sunovion Respiratory Development Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 641
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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 on-going 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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• COPD
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• SUN-101 50 mcg BID eFlow (CS) nebulizer
SUN-101 50 mcg twice daily (BID) eFlow (R) Closed System (CS) nebulizer
• SUN-101 25 mcg BID eFlow (CS) nebulizer
SUN-101 25 mcg BID eFlow (R) Closed System (CS) nebulizer
• Placebo eFlow (CS) nebulizer
Placebo BID eFlow (R) Closed System (CS) nebulizer

Locations

Country	Name	City	State
United States	SEC Lung, LLC	Andalusia	Alabama
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Innovative Clinical Research	Broomfield	Colorado
United States	IMMUNOe International Research Centers	Centennial	Colorado
United States	Lowcountry Lung and Critical Care, PA	Charleston	South Carolina
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Remington-Davis, Inc	Columbus	Ohio
United States	Sridhar Guduri, MD	Dublin	Ohio
United States	Duluth Biomedical Research, LLC	Duluth	Georgia
United States	Easley Clinical Research	Easley	South Carolina
United States	Liliestol Research LLC	Fargo	North Dakota
United States	Gaffney Pharmaceutical Research	Gaffney	South Carolina
United States	Spectrum Medical Research, LLC	Gaffney	South Carolina
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	Pulmonary Associates, PA	Glendale	Arizona
United States	PharmQuest	Greensboro	North Carolina
United States	Clinical Research of Lake Norman	Huntersville	North Carolina
United States	Jasper Summit Research, LLC	Jasper	Alabama
United States	New Phase Research & Development	Knoxville	Tennessee
United States	Longmont Pulmonary and Critical Care	Longmont	Colorado
United States	Delaware Valley Clinical Research	Marlton	New Jersey
United States	LaPorte County Institute for Clinical Research	Michigan City	Indiana
United States	Minnesota Lung Center	Minneapolis	Minnesota
United States	Clinical Research of Charleston	Mount Pleasant	South Carolina
United States	George Stanley Walker, MD	New Orleans	Louisiana
United States	Health Research of Hampton Roads, Inc.	Newport News	Virginia
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Ribo Research, LLC dba Peninsula Research Inc.	Ormond Beach	Florida
United States	Phoenix Medical Research Institute, LLC	Peoria	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Allergy Associates Research Center	Portland	Oregon
United States	PMG Research of Raleigh, LLC	Raleigh	North Carolina
United States	Pulmonary Associates of Richmond, Inc	Richmond	Virginia
United States	Southeast Regional Research Group	Rincon	Georgia
United States	Asthma and Allergy Center of Chicago, SC	River Forest	Illinois
United States	CU Pharmaceutical Research	Rock Hill	South Carolina
United States	Center for Clinical Trials of Sacramento, Inc.	Sacramento	California
United States	CAR.E. Clinical Research	Saint Louis	Missouri
United States	The Clinical Research Center, LLC	Saint Louis	Missouri
United States	Institute of HealthCare Assessment, Inc	San Diego	California
United States	Hope Clinical Research	Seneca	South Carolina
United States	Multicare Pulmonary Specialists	Tacoma	Washington
United States	Clinical Research Consortium	Tempe	Arizona
United States	Southeastern Research Center, LLC	Winston-Salem	North Carolina
United States	Pulmonary Care Research Group, PA	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion Respiratory Development Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kerwin E, Donohue JF, Goodin T, Tosiello R, Wheeler A, Ferguson GT. Efficacy and safety of glycopyrrolate/eFlow(®) CS (nebulized glycopyrrolate) in moderate-to-very-severe COPD: Results from the glycopyrrolate for obstructive lung disease via electronic n — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.; 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).	baseline and Week 12
Primary	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12	On-treatment 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.; 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).	Week 12
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 (MAR).	baseline and Week 12
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.; 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).	baseline and Week 12
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).	baseline and Week 12
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).	baseline and Week 12
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).	Week 0-12
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.	Week 0-12
Secondary	Percentage of Subjects With Treatment Emergent Adverse Events (TEAE)	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.	Week 0-12
Secondary	Number of Subjects With Treatment Emergent Serious Adverse Events (SAE)	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.	Week 0-12
Secondary	Percentage of Subjects With Treatment Emergent Serious Adverse Events (SAE)	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.	Week 0-12
Secondary	Number of Subjects Who Discontinue Treatment Due to TEAE	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.	Week 0-12
Secondary	Percentage of Subjects Who Discontinue Treatment Due to TEAE	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.	Week 0-12
Secondary	Number of Subjects With Major Adverse Cardiac Events (MACE)	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)	Week 0-12
Secondary	Percentage of Subjects With Major Adverse Cardiac Events (MACE)	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)	Week 0-12
Secondary	Incidence Rate Per 1000 Person-years of Subjects With Major Adverse Cardiac Events (MACE)	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); 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.	Week 0-12