Clinical trial NCT02347774: Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Chronic Obstructive Pulmonary Disease
Keywords: Chronic Obstructive Pulmonary Disease
COPD
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-27
Enrollment: 641
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
timeFrame: baseline and Week 12
measure: Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12
timeFrame: baseline and Week 12
measure: Change From Baseline in Trough Forced Vital Capacity (FVC)Week 12
timeFrame: baseline and Week 12
measure: Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study
timeFrame: baseline and Week 12
measure: Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study
timeFrame: baseline and Week 12
measure: Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period
timeFrame: Week 0-12
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAE)
timeFrame: Week 0-12
measure: Percentage of Subjects With Treatment Emergent Adverse Events (TEAE)
timeFrame: Week 0-12
measure: Number of Subjects With Treatment Emergent Serious Adverse Events (SAE)
timeFrame: Week 0-12
measure: Percentage of Subjects With Treatment Emergent Serious Adverse Events (SAE)
timeFrame: Week 0-12
measure: Number of Subjects Who Discontinue Treatment Due to TEAE
timeFrame: Week 0-12
measure: Percentage of Subjects Who Discontinue Treatment Due to TEAE
timeFrame: Week 0-12
measure: Number of Subjects With Major Adverse Cardiac Events (MACE)
timeFrame: Week 0-12
measure: Percentage of Subjects With Major Adverse Cardiac Events (MACE)
timeFrame: Week 0-12
measure: Incidence Rate Per 1000 Person-years of Subjects With Major Adverse Cardiac Events (MACE)
timeFrame: Week 0-12
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: SEC Lung, LLC
state: Alabama
city: Jasper
country: United States
facility: Jasper Summit Research, LLC
state: Alabama
city: Glendale
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Peoria
country: United States
facility: Phoenix Medical Research Institute, LLC
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium
state: Arizona
city: Sacramento
country: United States
facility: Center for Clinical Trials of Sacramento, Inc.
state: California
city: San Diego
country: United States
facility: Institute of HealthCare Assessment, Inc
state: California
city: Broomfield
country: United States
facility: Innovative Clinical Research
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe International Research Centers
state: Colorado
city: Longmont
country: United States
facility: Longmont Pulmonary and Critical Care
state: Colorado
city: Ormond Beach
country: United States
facility: Ribo Research, LLC dba Peninsula Research Inc.
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Winter Park
country: United States
facility: Pulmonary Care Research Group, PA
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Duluth
country: United States
facility: Duluth Biomedical Research, LLC
state: Georgia
city: Rincon
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: River Forest
country: United States
facility: Asthma and Allergy Center of Chicago, SC
state: Illinois
city: Michigan City
country: United States
facility: LaPorte County Institute for Clinical Research
state: Indiana
city: New Orleans
country: United States
facility: George Stanley Walker, MD
state: Louisiana
city: Minneapolis
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Saint Louis
country: United States
facility: CAR.E. Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: The Clinical Research Center, LLC
state: Missouri
city: Marlton
country: United States
facility: Delaware Valley Clinical Research
state: New Jersey
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Huntersville
country: United States
facility: Clinical Research of Lake Norman
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center, LLC
state: North Carolina
city: Fargo
country: United States
facility: Liliestol Research LLC
state: North Dakota
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Columbus
country: United States
facility: Remington-Davis, Inc
state: Ohio
city: Dublin
country: United States
facility: Sridhar Guduri, MD
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Portland
country: United States
facility: Allergy Associates Research Center
state: Oregon
city: Charleston
country: United States
facility: Lowcountry Lung and Critical Care, PA
state: South Carolina
city: Easley
country: United States
facility: Easley Clinical Research
state: South Carolina
city: Gaffney
country: United States
facility: Gaffney Pharmaceutical Research
state: South Carolina
city: Gaffney
country: United States
facility: Spectrum Medical Research, LLC
state: South Carolina
city: Mount Pleasant
country: United States
facility: Clinical Research of Charleston
state: South Carolina
city: Rock Hill
country: United States
facility: CU Pharmaceutical Research
state: South Carolina
city: Seneca
country: United States
facility: Hope Clinical Research
state: South Carolina
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc.
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc
state: Virginia
city: Tacoma
country: United States
facility: Multicare Pulmonary Specialists
state: Washington
Study officials:
affiliation: Sunovion Respiratory Development
name: Respiratory Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: Kerwin E, Donohue JF, Goodin T, Tosiello R, Wheeler A, Ferguson GT. Efficacy and safety of glycopyrrolate/eFlow(R) CS (nebulized glycopyrrolate) in moderate-to-very-severe COPD: Results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 3 and 4 randomized controlled trials. Respir Med. 2017 Nov;132:238-250. doi: 10.1016/j.rmed.2017.07.011. Epub 2017 Jul 19.
citation: Ohar J, Tosiello R, Goodin T, Sanjar S. Efficacy and safety of a novel, nebulized glycopyrrolate for the treatment of COPD: effect of baseline disease severity and age; pooled analysis of GOLDEN 3 and GOLDEN 4. Int J Chron Obstruct Pulmon Dis. 2018 Dec 18;14:27-37. doi: 10.2147/COPD.S184808. eCollection 2019.
citation: Ferguson GT, Kerwin EM, Donohue JF, Ganapathy V, Tosiello RL, Bollu VK, Rajagopalan K. Health-Related Quality of Life Improvements in Moderate to Very Severe Chronic Obstructive Pulmonary Disease Patients on Nebulized Glycopyrrolate: Evidence from the GOLDEN Studies. Chronic Obstr Pulm Dis. 2018 Jun 6;5(3):193-207. doi: 10.15326/jcopdf.5.3.2017.0178.