Chronic Dosing Cross-Over Study to Assess the Efficacy and Safety of Glycopyrronium (PT001) in Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma

Exclusion Criteria

• 1. Life-Threatening Asthma: A subject must not have life-threatening asthma. Lifethreatening asthma is defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s) within the 12 months prior to Visit 1a (Screening).
• 2. Worsening Asthma: A subject must not have experienced a worsening of asthma that involved an emergency department visit, hospitalization, or use of oral/parenteral corticosteroids within 6 weeks of Screening (Visit 1a).
• 3. Seasonal or Exercise-Induced Asthma Alone: Subjects with only seasonal or exerciseinduced asthma are excluded from participation.
• 4. Concurrent Respiratory Disease: A subject must not have current evidence or diagnosis of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, chronic bronchitis, emphysema, COPD, or other respiratory abnormalities other than asthma.
• 5. Concurrent Conditions/Diseases: A subject with historical or current evidence of any clinically significant, or comorbid or uncontrolled condition or disease state that, in the opinion of the Investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.
• 6. Smoking History: Current smokers or former smokers who have stopped smoking within 6 months prior to enrollment or with a >10 pack year history of cigarettes, cigars, or pipe smoking. E-cigarettes and inhaled marijuana should be treated in the same manner as tobacco products.
• 7. Inhaled Anticholinergic Use: Subjects must not have used inhaled anticholinergics for at least the 2 weeks prior to Screening (Visit 1a).
• 8. Pregnant women or nursing mothers
• 9. Respiratory Tract Infection: Subjects who have had a respiratory tract infection within 6 weeks prior to Screening (Visit 1a). Subjects who develop a respiratory tract infection during the Screening Period must discontinue from the trial, but will be permitted to reenroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection).
• 10. Uncontrolled Hypertension: Subjects who, in the opinion of the Investigator, have clinically significant uncontrolled hypertension.
• 11. Liver Function: Subjects with abnormal liver function tests defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin ≥1.5 times the upper limit of normal on repeat testing.
• 12. Renal: a. Subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator (if treated and asymptomatic, the subject is eligible for enrollment). Subjects with a trans-urethral resection of prostate or full resection of the prostate within 6 months prior to Visit 1a are excluded from the study.
• b. Subjects with bladder neck obstruction or urinary retention that is clinically
• significant in the opinion of the Investigator.
• c. Subjects with a calculated creatinine clearance ≤30 mL/minute using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula [Levey, 2009] at Visit 1a
• and on repeat testing prior to Visit 3.
• Note: Subjects with overactive bladder syndrome treated with oral anticholinergics that have been on treatment for at least one month are allowed in the study.
• 13. Glaucoma: Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of glaucoma (non-angle closure), that in the opinion of the Investigator, has not been adequately treated will also be excluded. Subjects with previously diagnosed glaucoma who have intraocular pressure controlled with medication(s) are eligible. All medications approved for control of intraocular pressures are allowed including topical ophthalmic
• non-selective β-blockers such as betaxolol, carteolol, levobunolol, metipranolol, or timolol.
• 14. Cancer: Subjects who have cancer that has not been in complete remission for at least 5 years.
• Note: Subjects with squamous cell carcinoma and basal cell carcinoma of the skin that have been resected for cure are not considered exclusionary. Subjects with localized prostate cancer that in the opinion of the Investigator, has been adequately worked up, is clinically controlled, and the subject’s participation in the study would not represent a safety concern, are eligible.
• 15. Drug Allergy: Subjects who have a history of hypersensitivity to lactose, milk proteins, or to any component of the MDI or dry powder inhaler (DPI)
• 16. Substance Abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2-year period prior to Screening (Visit 1a).
• 17. Cardiac Conditions/Disease: Subjects with documented myocardial infarction within a year from the Screening (Visit 1a) are to be excluded. Subjects with a recent history of acute coronary syndrome, or who have undergone percutaneous coronary intervention or coronary artery bypass graft within 3 months of Screening (Visit 1a) are to be excluded.