Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD

This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter,
efficacy and safety trial of 12 weeks of treatment with nebulized SUN-101 using an
Investigational eFlow® Closed System (CS) nebulizer in approximately 645 subjects with
chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic
Obstructive Lung Disease (GOLD 2014) guidelines.

SUN-101 or placebo will be administered twice daily as an oral inhalation using the
investigational eFlow CS nebulizer. Approximately 150 subjects will be enrolled in the
substudy (at selected sites only). These subjects will be required to participate in serial
spirometry, vital signs, ECGs, and an additional Holter monitor assessment at Visit 6 (Week
12). This subset of subjects will be referred to as the Substudy Population.

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, eg, 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 oral, intravenous, or intramuscular 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 QTcF (> 450 msec for males and > 470 msec for females) during Screening
(Visit 1) as determined from the report provided by the central laboratory, 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