Effect of Ensifentrine Treatment on CAT Score

Prior treatment

• Hospitalizations for COPD (or COPD exacerbation), pneumonia, or other serious infection or treatment with oral or parenteral (oral, intravenous, or intramuscular) glucocorticoids within the past 12 weeks.
• Major surgery (requiring general anesthesia) within the past 6 weeks, lack of full recovery from surgery, or planned surgery through the end of the study.
• Concomitant clinically significant pulmonary disease other than COPD (e.g., asthma, tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea (unless controlled with stable continuous positive airway pressure \[CPAP\] use), known alpha-1 antitrypsin deficiency, core pulmonale or other non-specific pulmonary disease).
• Severe comorbidities including unstable cardiac, (e.g., myocardial infarction within 1 year prior to screening, unstable angina within 6 months, or unstable or life-threatening arrhythmia requiring intervention within 3 months) or any other clinically significant medical conditions including uncontrolled diseases (e.g., endocrine, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric or ophthalmic diseases) 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.
• Previous lung resection or lung reduction surgery within 1-year.
• Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day.
• Use of prohibited medications, including nebulized medication, within the time intervals.
• Use of an experimental drug within 30 days or 5 half-lives, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days.
• A disclosed history or one known to the Investigator of significant noncompliance in previous investigational studies or with prescribed medications.

Other illness

• Lower respiratory tract infection within the past 6 weeks or an active infection.
• History of life-threatening COPD, including Intensive Care Unit admission and/or requiring intubation within 1-year.
• HIV infection or other immunodeficiency.
• History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin.
• Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator.
• Known diagnosis of severe chronic kidney disease.
• Current or history of drug or alcohol abuse within the past 5 years.

Lab values

• Known alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN), alkaline phosphatase and/or bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN is acceptable if fractionated bilirubin \< 35%).
• Any other known abnormal clinical, cardiac or laboratory (hematology, biochemistry or viral) findings, deemed by an investigator to be clinically significantly abnormal.

Other

• Pulmonary rehabilitation unless such treatment has been stable for at least 4 weeks and remains stable during the study.
• Findings on physical examination that an investigator considers to be clinically significant.
• Women who are breast feeding.
• Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days.
• Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned.
• Any other reason that the Investigator considers makes the subject unsuitable to participate.

• Capable of giving informed consent.
• Current or former cigarette smokers with a history of cigarette smoking ≥ 10 pack years.
• Established clinical history of moderate to severe COPD.
• Pre- and post-albuterol FEV1/FVC ratio of \< 0.70.
• Post-albuterol FEV1 ≥ 30 % and ≤ 75% of predicted normal.
• ≥2 on the modified Medical Research Council (mMRC) Dyspnea Scale.
• ≥10 on the COPD Assessment Test™.
• Taking stable dual (LAMA+LABA) or triple (LAMA+LABA+ICS) maintenance therapy for at least 8 weeks.
• Capable of using a standard jet nebulizer and performed spirometry assessment.