A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD

Exclusion Criteria24

• Concomitant clinically significant pulmonary disease other than COPD (i.e., 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
• Within 6 months prior to randomization, a COPD exacerbation requiring hospitalization
• Within 3 months prior to randomization, use of oral or systemic therapies for COPD exacerbations (for example, oral, intravenous, or intramuscular glucocorticoids, antibiotics, theophylline, and roflumilast)
• History of life-threatening COPD, including Intensive Care Unit admission and/or requiring intubation
• Severe comorbidities including
• unstable cardiac disease (myocardial infarction within 1 year prior to randomization, unstable angina within 6 months prior to randomization, unstable or life-threatening arrhythmia requiring intervention within 3 months prior to randomization, diagnosis of New York Heart Association (NYHA) class III or IV heart disease, or
• any other clinically significant medical conditions including uncontrolled diseases (e.g., endocrine, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric \[e.g. untreated significant depression, anxiety or history of suicidality\], 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
• History of or clinically significant on-going bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within 6 months prior to randomization
• History of narrow angle glaucoma
• History of hypersensitivity or intolerance to aerosol medications, albuterol, ensifentrine, or glycopyrrolate or any of its excipients/components, anticholinergic agents, or sympathomimetic amines
• History of or current malignancy of any organ system, treated or untreated within the 5 years prior to randomization, except for localized basal or squamous cell carcinoma of the skin
• Other significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator
• Findings on physical examination that an investigator considers to be clinically significant or abnormal during the Screening Period including hematology, biochemistry, viral serology, and ECG
• Prior or current use of Ohtuvayre (ensifentrine)
• Previous lung resection or lung reduction surgery within 1-year of randomization
• Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day. As needed oxygen use (≤ 12 hours per day) is not exclusionary
• Pulmonary rehabilitation unless such treatment has been stable from 4 weeks prior to signing the ICF and plans to remain stable during the study. Pulmonary rehabilitation programs should not be started or completed during participation in the study
• Major surgery (requiring general anesthesia) in the 6 weeks prior randomization, lack of full recovery from surgery at randomization, or planned surgery through the end of the study
• Current or history of drug or alcohol abuse within the 5 years prior to randomization
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min as tested during the Screening Period
• Alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≥ 2 × ULN, alkaline phosphatase and/or total bilirubin \> 1.5 × ULN (subjects with Gilbert's syndrome can be included with total bilirubin \>1.5 × ULN as long as direct bilirubin is ≤ 1.5 × ULN)
• Use of an experimental drug within 30 days or 5 half-lives of signing the ICF, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days prior to signing the ICF
• Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days prior to informed consent
• 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