Clinical trial NCT02347761: Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD
Official title: 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-3 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Keywords: Chronic Obstructive Pulmonary Disease
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-27
Enrollment: 653
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. 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.

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 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

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: Baseline and Week 12
Secondary outcomes:
measure: Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population
timeFrame: Baseline and Week 12
measure: Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population
timeFrame: Baseline and Week 12
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 Major Adverse Cardiac Events (MACE)
timeFrame: Week 0-12
measure: Percentage of Subjects With Major Cardiac Events (MACE)
timeFrame: Week 0-12
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAE)
timeFrame: Week 0-12
measure: Percent 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: Percent 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: Percent of Subjects Who Discontinue Treatment Due to TEAE
timeFrame: Week 0-12
measure: Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE)
timeFrame: Week 0-12
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium - Arizona
state: Arizona
city: Tucson
country: United States
facility: Desert Sun Clinical Research, LLC
state: Arizona
city: Wheat Ridge
country: United States
facility: Western States Clinical Research, Inc.
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Clermont
country: United States
facility: Clermont Medical Research
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists, PA, d/b/a PDS Research
state: Florida
city: Miami
country: United States
facility: AppleMed Research, Inc.
state: Florida
city: Miami
country: United States
facility: Clinical Trials of Florida, LLC
state: Florida
city: Orlando
country: United States
facility: Florida Institute for Clinical Research, LLC
state: Florida
city: Panama City
country: United States
facility: Emerald Coast Research Associates
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc
state: Florida
city: Fort Mitchell
country: United States
facility: Abraham Reasearch, PLLC
state: Kentucky
city: Livonia
country: United States
facility: Pulmonary Research Institute of Southeast Michigan
state: Michigan
city: Edina
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Saint Charles
country: United States
facility: Midwest Chest Consultants, P.C.
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Consortium
state: Nevada
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Charlotte
country: United States
facility: American Health Research, Inc.
state: North Carolina
city: Hickory
country: United States
facility: Hickory Research Center
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Ohio
city: Columbus
country: United States
facility: Columbus Clinical Research, Inc
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Pittsburgh
country: United States
facility: Research Protocol Management Specialists
state: Pennsylvania
city: East Providence
country: United States
facility: Safe Harbor Clinical Research
state: Rhode Island
city: Easley
country: United States
facility: Palmetto Medical Research Associates, LLC
state: South Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research, Inc
state: South Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Indian Land
country: United States
facility: Piedmont Research Partners, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: S. Carolina Pharmaceutical Research
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Union
country: United States
facility: CU Pharmaceutical Research
state: South Carolina
city: Fort Worth
country: United States
facility: Texas Pulmonary and Critical Care Consultants, PA
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
city: Abingdon
country: United States
facility: Pulmonary Research of Abingdon, LLC
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
Study officials:
affiliation: Sunovion Respiratory Director
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.