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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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)

Conditions
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COPD

Intervention / Treatment
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* Drug: Placebo
* Drug: EP-101 12.5 mcg
* Drug: EP-101 25 mcg
* Drug: EP-101 50 mcg
* Drug: EP-101 100 mcg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: EP-101 Placebo<br>EP-101 Placebo AM + EP-101 Placebo PM | Drug: Placebo<br>* EP-101 Placebo AM + EP-101 Placebo PM<br>* Other names: SUN101;|
| Experimental: EP 101 12.5 mcg<br>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM | Drug: EP-101 12.5 mcg<br>* EP-101 12.5 mcg AM + EP-101 12.5 mcg PM<br>* Other names: SUN101;|
| Experimental: EP-101 25 mcg<br>EP-101 25 mcg AM + EP-101 25 mcg PM | Drug: EP-101 25 mcg<br>* EP-101 25 mcg AM + EP-101 25 mcg PM<br>* Other names: SUN101;|
| Experimental: EP-101 50 mcg<br>EP-101 50 mcg AM + EP-101 50 mcg PM | Drug: EP-101 50 mcg<br>* EP-101 50 mcg AM + EP-101 50 mcg PM<br>* Other names: SUN101;|
| Experimental: EP-101 100 mcg<br>EP-101 100 mcg AM + EP-101 100 mcg PM | Drug: EP-101 100 mcg<br>* EP-101 100 mcg AM + EP-101 100 mcg PM<br>* Other names: SUN101;|

What is the study measuring?
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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 |