A Study of the Efficacy and Safety of EP-101 ( (SUN101) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease

COPD Clinical Trial

— GOLDEN-2  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of EP-101 (SUN101) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease: GOLDEN-2 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01706536
• Other study ID #: EP-101-04 (SUN101)
• Status: Completed
• Phase: Phase 2
• First received: October 10, 2012
• Last updated: February 6, 2018
• Start date: October 2012
• Est. completion date: April 2013

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 randomized, double-blind, placebo-controlled, parallel arm study. The study population will consist of subjects, 35 to 75 years of age, with a diagnosis of moderate to severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines.

Description:

This is a randomized, double-blind, placebo-controlled, parallel arm study. The study population will consist of subjects, 35 to 75 years of age, with a diagnosis of moderate to severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011). The primary analysis will compare each of the EP-101 (SUN101) dose groups to placebo with respect to the change from baseline in morning trough FEV1 on Day 29. Trough FEV1 is defined as the mean of the two FEV1 values obtained at 23 hours 30 minutes and 24 hours after Day 28 AM dose (ie, approximately 12 hours after the previous PM dose).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male and female subjects age 35 through 75 years, inclusive.

• A clinical diagnosis of moderate to severe COPD according to GOLD guidelines (2011).

• Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent).

• Post-bronchodilator (following inhalation of ipratropium bromide MDI) FEV1 = 30% and = 70% of predicted normal value during the Screening Period.

• Post-bronchodilator (following inhalation of ipratropium bromide MDI) FEV1/FVC ratio < 0.70 during the Screening Period.

• Post-bronchodilator (following inhalation of ipratropium bromide MDI) improvement in FEV1 = 12% and = 100 mL during the Screening Period.

• Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005).

• Subject, if female = 65 years of age and of child bearing potential, must have a negative serum pregnancy test at screening. 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 study participation.

• b. Barrier method of contraception, eg, condom and/or diaphragm with spermicide while participating in the study.

• c. Abstinence.

• Willing and able to provide written informed consent.

Exclusion Criteria:

• Current evidence or recent history of any clinically significant and unstable disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities.

• Current evidence or history of clinically significant abnormal cardiac rhythm and/or conduction findings, including Holter monitoring results during the Screening Period.

• Concomitant pulmonary disease or primary diagnosis of asthma.

• 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

• Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to the Screening Period.

• Use of daily oxygen therapy > 10 hours per day.

• Use of systemic steroids within 3 months prior to the Screening Period.

• Respiratory tract infection within 6 weeks prior to or during the Screening Period.

• History of tuberculosis, bronchiectasis or other non-specific pulmonary disease.

• History of urinary retention or bladder neck obstruction type symptoms.

• History of narrow-angle glaucoma.

• Prolonged QTc interval (> 450msec for males and > 470msec for females) during the Screening Period, or history of long QT syndrome.

• Recent history (previous 12 months) of excessive use or abuse of narcotic/illegal drugs.

• History of hypersensitivity or intolerance to ß2-agonists or anticholinergics.

• Participation in another investigational drug study where drug was received within 30 days prior to the Screening Period.

• Female subject who is pregnant or lactating

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
EP-101 Placebo AM + EP-101 Placebo PM
• EP-101 12.5 mcg
EP-101 12.5 mcg AM + EP-101 12.5 mcg PM
• EP-101 25 mcg
EP-101 25 mcg AM + EP-101 25 mcg PM
• EP-101 50 mcg
EP-101 50 mcg AM + EP-101 50 mcg PM
• EP-101 100 mcg
EP-101 100 mcg AM + EP-101 100 mcg PM

Locations

Country	Name	City	State
United States	Georgia Clinical Research	Austell	Georgia
United States	American Health Research	Charlotte	North Carolina
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Clinical Research of West Florida	Clearwater	Florida
United States	California Research Medical Group, Inc.	Fullerton	California
United States	Greenville Pharmaceutical Research, Inc	Greenville	South Carolina
United States	Upstate Pharmaceutical Research	Greenville	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Jasper Summit Research, LLC	Jasper	Alabama
United States	Gwinnett Biomedical Research	Lawrenceville	Georgia
United States	UCLA David Geffen School of Medicine	Los Angeles	California
United States	Clinical Research Institute of Southern Oregon, PC	Medford	Oregon
United States	Sunstone Medical Research LLC	Medford	Oregon
United States	Minnesota Lung Center	Minneapolis	Minnesota
United States	Central Texas Health Research	New Braunfels	Texas
United States	Pulmonary Associates, PA	Phoenix	Arizona
United States	Allergy Associates Research Center	Portland	Oregon
United States	North Carolina Clinical Research	Raleigh	North Carolina
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	Integrated Research Group	Riverside	California
United States	Capital Allergy & Respiratory Disease Center	Sacramento	California
United States	Institute of HealthCare Assessment, Inc.	San Diego	California
United States	South Carolina Pharmaceutical Research	Spartanburg	South Carolina
United States	Clinical Research of West Florida	Tampa	Florida
United States	Veritas Clinical Specialities, LTD	Topeka	Kansas
United States	CU Pharmacuetical Research	Union	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion Respiratory Development Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Donohue JF, Goodin T, Tosiello R, Wheeler A. Dose selection for glycopyrrolate/eFlow(®) phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies. Respir Res. 2017 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours after the in-clinic morning dose (i.e. approximately 12 hrs after the previous evening dose).	Baseline and Day 29
Secondary	The Standardized Change From Baseline FEV1 AUC(0-12)	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.	Day 28
Secondary	The Standardized Change From Baseline FEV1 AUC(12-24)	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.	Day 28
Secondary	The Peak FEV1 Change From Baseline	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Peak FEV1 is defined as the highest postdose FEV1 value within 4 hrs after the morning dose.	Day 28
Secondary	The Number of Subjects With Treatment-emergent Adverse Events	Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.	Baseline up to Day 28
Secondary	The Number of Subjects With Treatment-emergent Serious Adverse Events	Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.	Baseline up to Day 28
Secondary	The Number of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation	Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.	Baseline up to Day 28
Secondary	The Percentage of Subjects With Treatment-emergent Adverse Events	Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.	Baseline up to Day 28
Secondary	The Percentage of Subjects With Treatment-emergent Serious Adverse Events	Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.	Baseline up to Day 28
Secondary	The Percentage of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation	Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.	Baseline up to Day 28