A Phase IIb, Randomized, Double-blind, Placebo- Controlled, Parallel Group Study to Assess the Efficacy and Safety of Ensifentrine-glycopyrrolate Fixed-dose Combination at Two Dose Levels Compared to Glycopyrrolate or Ensifentrine Monotherapy in Subjects With COPD
This study will assess the safety and efficacy of fixed dose combinations of ensifentrine with two different glycopyrrolate dose levels compared to placebo and to the individual components of the fixed dose combinations, each administered twice a day via standard jet nebulizer, in adult subjects with chronic obstructive pulmonary disease (COPD).
• Males are eligible to participate if they agree to use contraception or abstinence, and refrain from donating fresh unwashed semen during the study and for at least 30 days post-study
• Females are eligible to participate if they are not pregnant, breastfeeding and if one of the following conditions apply:
‣ Not a woman of child-bearing potential OR
⁃ Agrees to follow the contraceptive guidance from screening throughout the study and for at least 30 days post-study
⁃ Agrees not to donate eggs for the purpose of reproduction from screening throughout the study and for at least 30 days post-study
• Current of former cigarette smokers with a history of smoking ≥ 10 pack years at the time of signing informed consent \[number of pack years = (number of cigarettes per day / 20) × number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to signing informed consent. Smoking cessation programs are permitted during the study
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD
• A score of ≥ 2 on the Modified Medical Research Council (mMRC) Dyspnea Scale at the Screening Visit
• Post-bronchodilator (4 puffs of albuterol) spirometry during the Screening Period demonstrating both the following:
‣ FEV1/forced vital capacity (FVC) ratio of \< 0.70 AND
⁃ FEV1 ≥ 30 % and ≤ 70% of predicted normal
• A posterior-anterior chest x-ray (CXR) during the Screening Period or within 12 months of signing the Informed Consent Form (ICF) showing no clinically significant abnormalities unrelated to COPD. If a CXR within the past 12 months is not available but a computed tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR
• Subjects on no maintenance/background therapy or subjects on stable maintenance as either long-acting β2-agonist (LABA) or long-acting β2-agonist/Inhaled corticosteroid (LABA/ICS) therapy are eligible. Subjects taking maintenance therapy must demonstrate regular use of maintenance therapy, in any form, for at least 60 days prior to signing informed consent and agree to continue use of their current permitted LABA or LABA/ICS medication for the duration of the screening and treatment period
• Capable of withholding from short-acting bronchodilators for 4 hours prior to spirometry testing. Subjects receiving maintenance therapy with a LABA or LABA/ICS must be capable of withholding twice-daily maintenance therapy for 24 hours and once-daily maintenance therapy for 48 hours prior to initiation of any spirometry
• Capable of using the study jet nebulizer correctly
• Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines
• Willing and able to attend all study visits and adhere to all study assessments and procedures