Clinical trial NCT01706536: A Study of the Efficacy and Safety of EP-101 ( (SUN101) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2012-10-15
Enrollment: 275
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and Day 29
Secondary outcomes:
measure: The Standardized Change From Baseline FEV1 AUC(0-12)
timeFrame: Day 28
measure: The Standardized Change From Baseline FEV1 AUC(12-24)
timeFrame: Day 28
measure: The Peak FEV1 Change From Baseline
timeFrame: Day 28
measure: The Number of Subjects With Treatment-emergent Adverse Events
timeFrame: Baseline up to Day 28
measure: The Number of Subjects With Treatment-emergent Serious Adverse Events
timeFrame: Baseline up to Day 28
measure: The Number of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation
timeFrame: Baseline up to Day 28
measure: The Percentage of Subjects With Treatment-emergent Adverse Events
timeFrame: Baseline up to Day 28
measure: The Percentage of Subjects With Treatment-emergent Serious Adverse Events
timeFrame: Baseline up to Day 28
measure: The Percentage of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation
timeFrame: Baseline up to Day 28
Other outcomes:
Locations:
city: Jasper
country: United States
facility: Jasper Summit Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Fullerton
country: United States
facility: California Research Medical Group, Inc.
state: California
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine
state: California
city: Riverside
country: United States
facility: Integrated Research Group
state: California
city: Sacramento
country: United States
facility: Capital Allergy & Respiratory Disease Center
state: California
city: San Diego
country: United States
facility: Institute of HealthCare Assessment, Inc.
state: California
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Austell
country: United States
facility: Georgia Clinical Research
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Biomedical Research
state: Georgia
city: Topeka
country: United States
facility: Veritas Clinical Specialities, LTD
state: Kansas
city: Minneapolis
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Charlotte
country: United States
facility: American Health Research
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Medford
country: United States
facility: Sunstone Medical Research LLC
state: Oregon
city: Portland
country: United States
facility: Allergy Associates Research Center
state: Oregon
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research, Inc
state: South Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Spartanburg
country: United States
facility: South Carolina Pharmaceutical Research
state: South Carolina
city: Union
country: United States
facility: CU Pharmacuetical Research
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
Study officials:
affiliation: Sunovion Respiratory Development
name: Respiratory Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: 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.