A Study of the Efficacy and Safety of EP-101 ( (SUN101) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (GOLDEN-2)

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)

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Placebo; Drug: EP-101 12.5 mcg; Drug: EP-101 25 mcg; Drug: EP-101 50 mcg; Drug: EP-101 100 mcg

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Jasper, Alabama, United States, 35501
      • Jasper Summit Research, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, PA
  • California
    • Fullerton, California, United States, 92835
      • California Research Medical Group, Inc.
    • Los Angeles, California, United States, 90095
      • UCLA david geffen school of medicine
    • Riverside, California, United States, 92506
      • Integrated Research Group
    • Sacramento, California, United States, 95819
      • Capital Allergy & Respiratory Disease Center
    • San Diego, California, United States, 92120
      • Institute of HealthCare Assessment, Inc.
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida
  • Georgia
    • Austell, Georgia, United States, 30106
      • Georgia Clinical Research
    • Lawrenceville, Georgia, United States, 30046
      • Gwinnett Biomedical Research
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Veritas Clinical Specialities, LTD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minnesota Lung Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • American Health Research
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon, PC
    • Medford, Oregon, United States, 97504
      • Sunstone Medical Research LLC
    • Portland, Oregon, United States, 97202
      • Allergy Associates Research Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Upstate Pharmaceutical Research
    • Greenville, South Carolina, United States, 29615
      • Greenville Pharmaceutical Research, Inc
    • Spartanburg, South Carolina, United States, 29303
      • South Carolina Pharmaceutical Research
    • Union, South Carolina, United States, 29379
      • CU Pharmacuetical Research
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • New Braunfels, Texas, United States, 78130
      • Central Texas Health Research
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Pulmonary Associates of Richmond, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 β2-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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: EP-101 Placebo; EP-101 Placebo AM + EP-101 Placebo PM	Drug: Placebo; EP-101 Placebo AM + EP-101 Placebo PM; Other Names: SUN101
Experimental: EP 101 12.5 mcg; EP-101 12.5 mcg AM + EP-101 12.5 mcg PM	Drug: EP-101 12.5 mcg; EP-101 12.5 mcg AM + EP-101 12.5 mcg PM; Other Names: SUN101
Experimental: EP-101 25 mcg; EP-101 25 mcg AM + EP-101 25 mcg PM	Drug: EP-101 25 mcg; EP-101 25 mcg AM + EP-101 25 mcg PM; Other Names: SUN101
Experimental: EP-101 50 mcg; EP-101 50 mcg AM + EP-101 50 mcg PM	Drug: EP-101 50 mcg; EP-101 50 mcg AM + EP-101 50 mcg PM; Other Names: SUN101
Experimental: EP-101 100 mcg; EP-101 100 mcg AM + EP-101 100 mcg PM	Drug: EP-101 100 mcg; EP-101 100 mcg AM + EP-101 100 mcg PM; Other Names: SUN101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Standardized Change From Baseline FEV1 AUC(0-12)	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.	Day 28
The Standardized Change From Baseline FEV1 AUC(12-24)	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.	Day 28
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Sunovion Respiratory Development Inc.
• Investigators: Study Director: Respiratory Medical Director, MD, Sunovion Respiratory Development

Publications and helpful links

General Publications

• Donohue JF, Goodin T, Tosiello R, Wheeler A. Dose selection for glycopyrrolate/eFlow(R) phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies. Respir Res. 2017 Dec 4;18(1):202. doi: 10.1186/s12931-017-0681-z.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: October 10, 2012
• First Submitted That Met QC Criteria: October 10, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Actual): March 8, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: EP-101-04 (SUN101)