Clinical trial NCT02276222: A Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD
Official title: A Randomized, Open-Label, Active-Controlled, Parallel-Group, Multicenter, Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD: GOLDEN-5 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Chronic Obstructive Pulmonary Disease
COPD
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-28
Enrollment: 1087
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 long-term safety trial of 48 weeks. Eligible subjects will enter the 48-week, open-label treatment period to receive one of two treatments (SUN-101 given as 50 mcg twice a day or Spiriva® \[tiotropium\] given as 18 mcg once a day).

Detailed description: This is a Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter, long-term safety trial of 48 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer or Spiriva in approximately 1050 subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines.

Eligible subjects will enter the 48-week, open-label treatment period following randomization to receive one of two treatments (SUN-101 given as 50 mcg BID or Spiriva® \[tiotropium\] given as 18 mcg QD).

The hypothesis for this study is that the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subjects randomized to SUN-101 is numerically similar to the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subject randomized to Spiriva (tiotropium).

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, e.g., 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 systemic 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 QTc (\> 450 msec for males and \> 470 msec for females) during Screening (Visit 1), 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: Number of Subjects With Treatment-emergent Adverse Events (TEAE)
timeFrame: Up to Week 48
measure: Percentage of Subjects With Treatment-emergent Adverse Events
timeFrame: Up to Week 48
measure: Number of Subjects With Treatment-emergent Serious Adverse Events (SAE)
timeFrame: Up to Week 48
measure: Percentage of Subjects With Treatment-emergent Serious Adverse
timeFrame: Up to Week 48
measure: Number of Subjects Who Discontinue the Study Due to TEAE
timeFrame: Up to Week 48
measure: Percentage of Subjects Who Discontinue the Study Due to TEAE
timeFrame: Up to 48 Weeks
Secondary outcomes:
measure: Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke
timeFrame: Up to Week 48
measure: Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke
timeFrame: Up to 48 Weeks
measure: Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke
timeFrame: up to week 48
measure: Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: SEC Lung LLC
state: Alabama
city: Birmingham
country: United States
facility: Achieve Clinical Research LLC
state: Alabama
city: Jasper
country: United States
facility: Jasper Summit Research LLC
state: Alabama
city: Chandler
country: United States
facility: Clinical Research Advantage, Inc.lEast Valley Family Physicians, PLC
state: Arizona
city: Tucson
country: United States
facility: Desert Sun Clinical Research LLC
state: Arizona
city: Fountain Valley
country: United States
facility: Allianz Research Institute, Inc.
state: California
city: Fresno
country: United States
facility: Research Center of Fresno, Inc.
state: California
city: Fullerton
country: United States
facility: California Research Medical Group, lnc.
state: California
city: Los Angeles
country: United States
facility: Southern California Institute For Respiratory Diseases, Inc.
state: California
city: Riverside
country: United States
facility: Integrated Research Group, Inc
state: California
city: San Diego
country: United States
facility: Institute of Healthcare Assessments Inc.
state: California
city: Waterbury
country: United States
facility: Waterbury Pulmonary Associates, LLC
state: Connecticut
city: Brandon
country: United States
facility: Tampa Bay Clinical Research Center
state: Florida
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, llC
state: Florida
city: Hialeah
country: United States
facility: The Community Research of South Florida
state: Florida
city: Miami
country: United States
facility: AppleMed Research, Inc
state: Florida
city: Miami
country: United States
facility: Research Institute of South Florida, 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: Ormond Beach
country: United States
facility: Ribo Research, LLC dba Peninsula Research, Inc.
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Vero Beach
country: United States
facility: Vero Lung Center
state: Florida
city: Lawrenceville
country: United States
facility: Gwinnett Biomedical Research
state: Georgia
city: Coeur d'Alene
country: United States
facility: H.C. Research LLC
state: Idaho
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
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: Valparaiso
country: United States
facility: Buynak Clinical Research, P.C.
state: Indiana
city: Fort Mitchell
country: United States
facility: Abraham Research, PLLC
state: Kentucky
city: Hazard
country: United States
facility: Kentucky Lung Clinics, PSC
state: Kentucky
city: Lafayette
country: United States
facility: Bendel Medical Research Center, LLC
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans Center for Clinical Research
state: Louisiana
city: Columbia
country: United States
facility: Howard County Center for Lung and Sleep Medicine, LLC
state: Maryland
city: Towson
country: United States
facility: Pulmonary and Critical Care Associates of Baltimore
state: Maryland
city: Cadillac
country: United States
facility: Cadillac Clinical Research LLC
state: Michigan
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: Minneapolis
country: United States
facility: Clinical Research Institute, Inc.
state: Minnesota
city: Minneapolis
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 PC
state: Missouri
city: Saint Louis
country: United States
facility: CARE Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: Midwest Clinical Research LLC
state: Missouri
city: Saint Louis
country: United States
facility: The Clinical Research Center
state: Missouri
city: Lincoln
country: United States
facility: Somnos Laboratories, Inc d/b/a Somnos Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Advantage Inc
state: Nevada
city: Marlton
country: United States
facility: Delaware Valley Clinical Research, LLC
state: New Jersey
city: Ocean City
country: United States
facility: Atlantic Research Center, LLC
state: New Jersey
city: Summit
country: United States
facility: Pulmonary and Allergy Associates, PA
state: New Jersey
city: Jamaica
country: United States
facility: ISA Clinical Research
state: New York
city: Charlotte
country: United States
facility: American Health Research, Inc.
state: North Carolina
city: Huntersville
country: United States
facility: ARSM Research
state: North Carolina
city: Huntersville
country: United States
facility: Clinical Research of Lake Norman
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, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research, LLC
state: North Dakota
city: Cincinnati
country: United States
facility: IVA Researcb
state: Ohio
city: Columbus
country: United States
facility: Remington Davis Inc
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Medford
country: United States
facility: Sunstone Medical Research, L.LC
state: Oregon
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: Easley
country: United States
facility: Palmetto Medical Research Associates
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: Greenville
country: United States
facility: Greenville Pharmaceutical Research, Inc.
state: South Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research, Inc.
state: South Carolina
city: Greer
country: United States
facility: DeGarmo Institute of Medical Research
state: South Carolina
city: Mount Pleasant
country: United States
facility: Clinical Research of Charleston
state: South Carolina
city: Seneca
country: United States
facility: Hope Clinical Research
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: Knoxville
country: United States
facility: New Phase Clinical Research & Development
state: Tennessee
city: Corsicana
country: United States
facility: Corsicana Medical Research, PLLC
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc
state: Texas
city: San Antonio
country: United States
facility: Alamo Clinical Research Associates
state: Texas
city: Tacoma
country: United States
facility: Pulmonary Consultants PLLC
state: Washington
city: Beroun
country: Czechia
facility: Medicentrum Beroun s.r o.
city: Jindřichův Hradec
country: Czechia
facility: MediTrial, s.r.o Internf a pneumoloqicka ambulance
city: Kyjov
country: Czechia
facility: Nemocnice Kyjov, p.o.
city: Neratovice
country: Czechia
facility: Plicni ambulance
city: Ostrava - Poruba
country: Czechia
facility: MephaCentrum, a s Plicni oddeleni
city: Ostrava-Poruba
country: Czechia
facility: MephaCentrum, a.s.
city: Praha
country: Czechia
facility: PNEUMa-HOST s LO.
city: Rokycany
country: Czechia
facility: PLiCNI AMBULANCE ROKYCANY, s.r o.
city: Zatec
country: Czechia
facility: Hrudnf ambulance s.r.o.
city: Balassagyarmat
country: Hungary
facility: Dr. Kenessey Albert Korhaz-Rendetointezet, TOd6gy6gyaszati
city: Csorna
country: Hungary
facility: Csornai Margit Korhaz, TOd6gy6gyaszat
city: Debrecen
country: Hungary
facility: Kenezy Gyula Korhaz es Rendelomtezet, Klinikai Farmakologiai
city: Farkasgyepű
country: Hungary
facility: Veszprern Megyei Tudbgyogyintezet
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi M6r Oktat6 Korhaz, Tudoqondozo
city: Kapuvar
country: Hungary
facility: Lumniczer Sandor Korhaz as Rendelointezet, Tudoqondozo
city: Komárom
country: Hungary
facility: Selye Janos Korhaz es Rendelointezet, Tud6gy6gyaszati Szakrendeles
city: Monor
country: Hungary
facility: Szakorvosi Rendelointezet Monor, Tudoqondozo
city: Nyiregyhaza
country: Hungary
facility: Revamed Eqeszsequqyi Szolqaltato Kft.
city: Siofok
country: Hungary
facility: Si6fok Kornaz-Rendelointezet, Tudoqondozo
city: Szazhalombatta
country: Hungary
facility: Farmakontroll Egeszsegugyi Szolqaltato Bt
city: Szeged
country: Hungary
facility: Csonqrad Megyei Mellkasi Beteqseqek Szakkorhaza, Tudoqondozo lntezet
city: Barnaul
country: Russian Federation
facility: Territorial SBI of Healthcare <Territorial Clinical Hospital>
city: Blagoveshchensk
country: Russian Federation
facility: FSBI Far Eastern Research Centre ofPhysiology and Pathology of Breathing of Siberian branch of RAMS
city: Chelyabinsk
country: Russian Federation
facility: SBI of Healthcare Regional Clinical Hospital #4 City consultative department for pulmonological patientsr
city: Ekaterinburg
country: Russian Federation
facility: Municipal Autonomous Institution (City ClinicalHospital #14)
city: Kemerovo
country: Russian Federation
facility: Municipal Budget Institution of Healthcare (City Clinical Hospital #3 n.a. M.A. Podgorbunsky)
city: Kemerovo
country: Russian Federation
facility: FSSI Scientific Research Institute of Complex Cardiovascular Pathology
city: Moscow
country: Russian Federation
facility: FSBI
city: Moscow
country: Russian Federation
facility: Non-State Private Institution of Healthcare <Scientific Clinical Center>
city: Nizhny-Novgorod
country: Russian Federation
facility: SBI of Healthcare of Nizhny-Novgorod region
city: Novosibirsk
country: Russian Federation
facility: SB1 of Healthcare of Novosibirsk region <Novosibirsk State Regional Clinical Hospital>l
city: Novosibirsk
country: Russian Federation
facility: SBI of Healthcare of Novosibirsk region <Novosibirsk State Regional Clinical Hospital>
city: Saint-Petersburg
country: Russian Federation
facility: SBEI of HPE <North-West State Medical University n.a. LL Mechnikov>
city: St. Petersburg
country: Russian Federation
facility: Alliance Biomedical, Russian Group LLC
city: Yaroslavl
country: Russian Federation
facility: SBr of Helathcareof Yaraslavl region Clinical Hospital of Emervency care n.a.N.V. Solovyev
Study officials:
affiliation: Sunovion Respiratory Development
name: Respiratory Medical Director
role: STUDY_DIRECTOR
References:
citation: Ferguson GT, Goodin T, Tosiello R, Wheeler A, Kerwin E. Long-term safety of glycopyrrolate/eFlow(R) CS in moderate-to-very-severe COPD: Results from the Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer (GOLDEN) 5 randomized study. Respir Med. 2017 Nov;132:251-260. doi: 10.1016/j.rmed.2017.08.020. Epub 2017 Aug 24.
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.