A Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— GOLDEN-5  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02276222
• Other study ID #: SUN101-303
• Status: Completed
• Phase: Phase 3
• First received: October 14, 2014
• Last updated: February 13, 2018
• Start date: October 2014
• Est. completion date: February 2016

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 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1087
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• 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, 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.

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 (Glycopyrrolate) 50 mcg twice daily (BID) via eFlow Closed System (CS) nebulizer
• Spiriva® 18 mcg QD Handihaler
Spiriva (tiotropium) 18 mcg once daily (QD) via Handihaler

Locations

Country	Name	City	State
Czechia	Medicentrum Beroun s.r o.	Beroun
Czechia	MediTrial, s.r.o Internf a pneumoloqicka ambulance	Jindrichuv Hradec
Czechia	Nemocnice Kyjov, p.o.	Kyjov
Czechia	Plicni ambulance	Neratovice
Czechia	MephaCentrum, a s Plicni oddeleni	Ostrava - Poruba
Czechia	MephaCentrum, a.s.	Ostrava-Poruba
Czechia	PNEUMa-HOST s LO.	Praha
Czechia	PLiCNI AMBULANCE ROKYCANY, s.r o.	Rokycany
Czechia	Hrudnf ambulance s.r.o.	Zatec
Hungary	Dr. Kenessey Albert Korhaz-Rendetointezet, TOd6gy6gyaszati	Balassagyarmat
Hungary	Csornai Margit Korhaz, TOd6gy6gyaszat	Csorna
Hungary	Kenezy Gyula Korhaz es Rendelomtezet, Klinikai Farmakologiai	Debrecen
Hungary	Veszprern Megyei Tudbgyogyintezet	Farkasgyepu
Hungary	Somogy Megyei Kaposi M6r Oktat6 Korhaz, Tudoqondozo	Kaposvar
Hungary	Lumniczer Sandor Korhaz as Rendelointezet, Tudoqondozo	Kapuvar
Hungary	Selye Janos Korhaz es Rendelointezet, Tud6gy6gyaszati Szakrendeles	Komárom
Hungary	Szakorvosi Rendelointezet Monor, Tudoqondozo	Monor
Hungary	Revamed Eqeszsequqyi Szolqaltato Kft.	Nyiregyhaza
Hungary	Si6fok Kornaz-Rendelointezet, Tudoqondozo	Siofok
Hungary	Farmakontroll Egeszsegugyi Szolqaltato Bt	Szazhalombatta
Hungary	Csonqrad Megyei Mellkasi Beteqseqek Szakkorhaza, Tudoqondozo lntezet	Szeged
Russian Federation	Territorial SBI of Healthcare <Territorial Clinical Hospital>	Barnaul
Russian Federation	FSBI Far Eastern Research Centre ofPhysiology and Pathology of Breathing of Siberian branch of RAMS	Blagoveshchensk
Russian Federation	SBI of Healthcare Regional Clinical Hospital #4 City consultative department for pulmonological patientsr	Chelyabinsk
Russian Federation	Municipal Autonomous Institution (City ClinicalHospital #14)	Ekaterinburg
Russian Federation	FSSI Scientific Research Institute of Complex Cardiovascular Pathology	Kemerovo
Russian Federation	Municipal Budget Institution of Healthcare (City Clinical Hospital #3 n.a. M.A. Podgorbunsky)	Kemerovo
Russian Federation	FSBI	Moscow
Russian Federation	Non-State Private Institution of Healthcare <Scientific Clinical Center>	Moscow
Russian Federation	SBI of Healthcare of Nizhny-Novgorod region	Nizhny-Novgorod
Russian Federation	SB1 of Healthcare of Novosibirsk region <Novosibirsk State Regional Clinical Hospital>l	Novosibirsk
Russian Federation	SBI of Healthcare of Novosibirsk region <Novosibirsk State Regional Clinical Hospital>	Novosibirsk
Russian Federation	SBEI of HPE <North-West State Medical University n.a. LL Mechnikov>	Saint-Petersburg
Russian Federation	Alliance Biomedical, Russian Group LLC	St. Petersburg
Russian Federation	SBr of Helathcareof Yaraslavl region Clinical Hospital of Emervency care n.a.N.V. Solovyev	Yaroslavl
United States	SEC Lung LLC	Andalusia	Alabama
United States	Achieve Clinical Research LLC	Birmingham	Alabama
United States	Tampa Bay Clinical Research Center	Brandon	Florida
United States	Cadillac Clinical Research LLC	Cadillac	Michigan
United States	Clinical Research Advantage, Inc.lEast Valley Family Physicians, PLC	Chandler	Arizona
United States	Lowcountry Lung and Critical Care, PA	Charleston	South Carolina
United States	American Health Research, Inc.	Charlotte	North Carolina
United States	IVA Researcb	Cincinnati	Ohio
United States	Clinical Research of West Florida	Clearwater	Florida
United States	H.C. Research LLC	Coeur d'Alene	Idaho
United States	Howard County Center for Lung and Sleep Medicine, LLC	Columbia	Maryland
United States	Remington Davis Inc	Columbus	Ohio
United States	Corsicana Medical Research, PLLC	Corsicana	Texas
United States	Avail Clinical Research, llC	DeLand	Florida
United States	Easley Clinical Research	Easley	South Carolina
United States	Palmetto Medical Research Associates	Easley	South Carolina
United States	Minnesota Lung Center	Edina	Minnesota
United States	Evanston Premier Healthcare Research LLC	Evanston	Illinois
United States	Lillestol Research, LLC	Fargo	North Dakota
United States	Abraham Research, PLLC	Fort Mitchell	Kentucky
United States	Allianz Research Institute, Inc.	Fountain Valley	California
United States	Research Center of Fresno, Inc.	Fresno	California
United States	California Research Medical Group, lnc.	Fullerton	California
United States	Gaffney Pharmaceutical Research	Gaffney	South Carolina
United States	Spectrum Medical Research, LLC	Gaffney	South Carolina
United States	Greenville Pharmaceutical Research, Inc.	Greenville	South Carolina
United States	Upstate Pharmaceutical Research, Inc.	Greenville	South Carolina
United States	DeGarmo Institute of Medical Research	Greer	South Carolina
United States	Kentucky Lung Clinics, PSC	Hazard	Kentucky
United States	The Community Research of South Florida	Hialeah	Florida
United States	Pioneer Research Solutions, Inc	Houston	Texas
United States	ARSM Research	Huntersville	North Carolina
United States	Clinical Research of Lake Norman	Huntersville	North Carolina
United States	ISA Clinical Research	Jamaica	New York
United States	Jasper Summit Research LLC	Jasper	Alabama
United States	New Phase Clinical Research & Development	Knoxville	Tennessee
United States	Bendel Medical Research Center, LLC	Lafayette	Louisiana
United States	Clinical Research Advantage Inc	Las Vegas	Nevada
United States	Gwinnett Biomedical Research	Lawrenceville	Georgia
United States	Somnos Laboratories, Inc d/b/a Somnos Clinical Research	Lincoln	Nebraska
United States	Pulmonary Research Institute of Southeast Michigan	Livonia	Michigan
United States	Southern California Institute For Respiratory Diseases, Inc.	Los Angeles	California
United States	Delaware Valley Clinical Research, LLC	Marlton	New Jersey
United States	Clinical Research Institute of Southern Oregon, PC	Medford	Oregon
United States	Sunstone Medical Research, L.LC	Medford	Oregon
United States	AppleMed Research, Inc	Miami	Florida
United States	Clinical Trials of Florida, LLC	Miami	Florida
United States	Research Institute of South Florida, Inc	Miami	Florida
United States	LaPorte County Institute For Clinical Research	Michigan City	Indiana
United States	Clinical Research Institute, Inc.	Minneapolis	Minnesota
United States	Minnesota Lung Center	Minneapolis	Minnesota
United States	Clinical Research of Charleston	Mount Pleasant	South Carolina
United States	New Orleans Center for Clinical Research	New Orleans	Louisiana
United States	Atlantic Research Center, LLC	Ocean City	New Jersey
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Florida Institute For Clinical Research, LLC	Orlando	Florida
United States	Ribo Research, LLC dba Peninsula Research, Inc.	Ormond Beach	Florida
United States	Allergy Associates Research Center	Portland	Oregon
United States	North Carolina Clinical Research	Raleigh	North Carolina
United States	Asthma and Allergy Center of Chicago SC	River Forest	Illinois
United States	Integrated Research Group, Inc	Riverside	California
United States	Midwest Chest Consultants PC	Saint Charles	Missouri
United States	CARE Clinical Research	Saint Louis	Missouri
United States	Midwest Clinical Research LLC	Saint Louis	Missouri
United States	The Clinical Research Center	Saint Louis	Missouri
United States	Alamo Clinical Research Associates	San Antonio	Texas
United States	Institute of Healthcare Assessments Inc.	San Diego	California
United States	Hope Clinical Research	Seneca	South Carolina
United States	S. Carolina Pharmaceutical Research	Spartanburg	South Carolina
United States	Spartanburg Medical Research	Spartanburg	South Carolina
United States	Pulmonary and Allergy Associates, PA	Summit	New Jersey
United States	Pulmonary Consultants PLLC	Tacoma	Washington
United States	Clinical Research of West Florida	Tampa	Florida
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	Pulmonary and Critical Care Associates of Baltimore	Towson	Maryland
United States	Desert Sun Clinical Research LLC	Tucson	Arizona
United States	CU Pharmaceutical Research	Union	South Carolina
United States	Buynak Clinical Research, P.C.	Valparaiso	Indiana
United States	Vero Lung Center	Vero Beach	Florida
United States	Waterbury Pulmonary Associates, LLC	Waterbury	Connecticut
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina
United States	Southeastern Research Center	Winston-Salem	North Carolina
United States	Minnesota Lung Center	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion Respiratory Development Inc.

Countries where clinical trial is conducted

United States,  Czechia,  Hungary,  Russian Federation, 

References & Publications (1)

Ferguson GT, Goodin T, Tosiello R, Wheeler A, Kerwin E. Long-term safety of glycopyrrolate/eFlow(®) CS in moderate-to-very-severe COPD: Results from the Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer (GOLDEN) 5 randomized study. Resp — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Treatment-emergent Adverse Events (TEAE)	A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.	Up to Week 48
Primary	Percentage of Subjects With Treatment-emergent Adverse Events	A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.	Up to Week 48
Primary	Number of Subjects With Treatment-emergent Serious Adverse Events (SAE)	A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date.	Up to Week 48
Primary	Percentage of Subjects With Treatment-emergent Serious Adverse	A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date.	Up to Week 48
Primary	Number of Subjects Who Discontinue the Study Due to TEAE	A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.	Up to Week 48
Primary	Percentage of Subjects Who Discontinue the Study Due to TEAE	A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date.	Up to 48 Weeks
Secondary	Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke	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 from the first date of study medication until the date of last contact.	Up to Week 48
Secondary	Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke	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 from the first date of study medication until the date of last contact.	Up to 48 Weeks
Secondary	Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke	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 from the first date of study medication until the date of last contact.	up to week 48
Secondary	Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects	Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the FEV1 values collected at the end of the dosing interval at each clinic visit. The mean change from baseline in trough FEV1 over the 48 week treatment period is calculated by averaging the trough FEV1 changes from baseline across all study visits while subjects are taking randomized treatment.; Values affected by other medication use were to be set to missing.	Up to Week 48