A Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD

This is a long-term safety trial of 48 weeks. Eligible subjects will enter the 48-week, open-label treatment period to receive one of two treatments (SUN-101 given as 50 mcg twice a day or Spiriva® \[tiotropium\] given as 18 mcg once a day).

This is a Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter, long-term safety trial of 48 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer or Spiriva in approximately 1050 subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines.

Eligible subjects will enter the 48-week, open-label treatment period following randomization to receive one of two treatments (SUN-101 given as 50 mcg BID or Spiriva® \[tiotropium\] given as 18 mcg QD).

The hypothesis for this study is that the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subjects randomized to SUN-101 is numerically similar to the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subject randomized to Spiriva (tiotropium).

Eligibility Criteria:
Inclusion Criteria:

1. Male or female patients age ≥ 40 years, inclusive.
2. A clinical diagnosis of COPD according to the GOLD 2014 guidelines.
3. Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent).
4. Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 \< 80% of predicted normal and \> 0.7 L during Screening (Visit 1).
5. Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio \< 0.70 during Screening (Visit 1).
6. Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005).
7. Subject, if female ≤ 65 years of age and of child bearing potential, must have a negative serum pregnancy test at Visit 1. 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 participation; b) barrier method of contraception, e.g., condom and /or diaphragm with spermicide while participating in the study; and/or c) abstinence..
8. Willing and able to provide written informed consent.
9. Willing and able to attend all study visits and adhere to all study assessments and procedures.

Exclusion Criteria:

1. Severe comorbidities including unstable cardiac or pulmonary disease or any other medical conditions that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject.
2. Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis or other non-specific pulmonary disease).
3. Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening (Visit 1).
4. Use of daily oxygen therapy \> 12 hours per day.
5. Respiratory tract infection within 6 weeks prior to Screening (Visit 1).
6. Use of systemic steroids within 3 months prior to Screening (Visit 1).
7. 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.
8. Prolonged QTc (\> 450 msec for males and \> 470 msec for females) during Screening (Visit 1), or history of long QT syndrome.
9. History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months.
10. History of narrow angle glaucoma.
11. History of hypersensitivity or intolerance to aerosol medications.
12. Recent documented history (within the previous 3 months) of substance abuse.
13. Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator.
14. Participation in another investigational drug study where drug was received within 30 days prior to Screening (Visit 1) or current participation in another investigational drug trial, including a SUN-101 study.
15. Previously received SUN-101 (active treatment; formerly known as EP-101).
16. Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, beta2 agonists, or sympathomimetic amines.