Study to Investigate the Dose Response, Safety and Efficacy of Nebulized EP-101(SUN101) in Patients With Chronic Obstructive Pulmonary Disease (COPD): GOLDEN-1 Study

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, four-period, incomplete block design cross-over study using EP-101(SUN101) and open-label active controls (tiotropium bromide and ipratropium bromide). The study population will consist of subjects of 40-75 years of age with moderate to severe COPD. Approximately 133 subjects diagnosed with moderate to severe COPD will be enrolled in order to achieve minimum 105 subjects completing the study.

Following a run-in phase, each subject will be randomly assigned to one of 7 treatment sequences,(96 sequences when order of administration is considered), with each sequence comprised of four 7-day Treatment Periods. There will be a washout period of 7 days between each Treatment Period. Study visits will be conducted on Days 1 and 7 of each Treatment Period, with an overnight stay required in the clinic during these visits. A Final Study Visit will be conducted 7 days following the last study treatment.

During each Treatment Period, study treatments will be administered once daily (QD), except for ipratropium inhalation solution, which will be administered three times daily (TID). EP-101 (SUN101)active and placebo treatments will be administered using an investigational high-efficiency eFlow® nebulizer. Tiotropium bromide (Spiriva®) will be administered in an open-label manner via Handihaler® dry-powder inhaler (DPI). Ipratropium bromide inhalation solution will be administered in an open-label manner via general purpose nebulizer.

This study was previously posted by Elevation Pharmaceuticals, Inc. On September 5, 2012, Elevation was acquired by merger with Sunovion Pharmaceuticals Inc. ("Sunovion"), which resulted in Elevation becoming a direct wholly-owned subsidiary of Sunovion. In conjunction with this acquisition, the name of Elevation has been changed to Sunovion Respiratory Development Inc.

Inclusion criteria

• 40-75 years of age
• Clinical diagnosis of moderate to severe COPD
• Current/ex-smokers with at least 10 pack-year smoking history
• Post-bronchodilator FEV1 ≥ 30% and ≤ 70% predicted normal values
• Post-bronchodilator FEV1/FVC ratio of ≤ 0.70
• Post-bronchodilator improvement in FEV1 ≥ 12% and ≤ 30%, and a minimum of 100 mL
• Willing and able to remain at the study site for at least 24 hours at each study visit
• Signed written informed consent

Exclusion criteria

• Current evidence or recent history of any clinically significant and unstable disease or abnormality (e.g., myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes)
• Primary diagnosis of asthma
• History of malignancy within the past 5 years
• History of COPD exacerbation within 6 weeks of Screening
• Daily oxygen therapy > 10 hours per day
• Systemic steroids use within 6 weeks of Screening
• Respiratory tract infection within 6 weeks of Screening
• History of tuberculosis, bronchiectasis
• History of urinary retention or bladder neck obstruction type symptoms
• History of glaucoma
• Prolonged QTc interval (>460msec) or history of long QT syndrome
• Recent history of alcohol or drug abuse
• Females who are pregnant or breastfeeding, or if of child-bearing potential unwilling to practice acceptable birth control methods
• History of hypersensitivity or intolerance to aerosol medications
• Participation in another investigational drug study within 30 days of Screening