Revefenacin in Chinese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease(COPD)

This study is a phase III clinical study to assess the efficacy and safety of Revefenacin inhalation solution 175 mcg administered once daily via nebulization for 12 weeks compared to placebo in a population of Chinese subjects with moderate to very severe COPD.

This will be a multi-center, randomized, double blind, placebo-controlled, parallel group study, randomizing approximately 320 male or female moderate-very severe COPD subjects. Subjects will receive study drug for 12 weeks. Treatments to be received during the study will include one of the following, administered using a centrally-provided, standard jet nebulizer and compressor via a mouthpiece: A. Revefenacin inhalation solution 175 mcg Quaque die (QD). B. Placebo inhalation solution QD. Subjects will have approximately 6 clinic visits (encompassing a screening period of up to 30 days and a treatment period of 12 weeks), and a follow-up telephone call 1-2 weeks after the End of Treatment (EoT) visit.

Eligibility Criteria:
Inclusion Criteria:

* Key inclusion criteria include:

  * Males and females of Chinese ethnicity, at least 40 years of age. Females may be of either childbearing or non-childbearing potential. All females of childbearing potential must be using an acceptable, highly effective method of contraception and have a negative pregnancy test at screening.
  * A clinical diagnosis for at least 6 months prior to screening of COPD according to Global Initiative for Chronic Obstructive Lung Disease(GOLD) guidelines.
  * Subject is capable of performing reproducible spirometry maneuvers as described by current American Thoracic Society/European Respiratory Society (ATS/ERS) Guidelines and has a post-ipratropium (500 mcg nebulized) Forced Expiratory Volume in

    1 second(FEV1)/Forced Vital Capacity(FVC) ratio \<0.7 at Visit 2.
  * Subject has moderate to very severe COPD with a post-ipratropium (500 mcg nebulized) FEV1 less than 80% of predicted normal (using the Global Lung Function Initiative reference range; ) and an absolute FEV1 \>700 mL at Visit 2
  * Current smoker or ex-smoker, with a history of at least 10 pack-years of tobacco smoking. Ex-smokers must have stopped smoking \>6 months prior to Visit 1.

Exclusion Criteria:

* Key exclusion criteria include:

  * Previously dosed with Revefenacin.
  * Current diagnosis of asthma.
  * Alpha-1 anti-trypsin deficiency.
  * Other chronic or active respiratory disorder (e.g., clinically significant \[as determined by the Investigator\] bronchiectasis, pulmonary fibrosis, sarcoidosis, pneumoconiosis, active tuberculosis).
  * Symptoms of, or treatment for an Acute Exacerbation of COPD(AECOPD) requiring antibiotics and/or oral/systemic corticosteroids or in-patient hospitalization during the 28 days preceding screening or during the screening period between Visit 1 and Visit 3.
  * Pneumonia requiring hospitalization within 28 days prior to screening or during the screening period between Visit 1 and Visit 3.
  * Lower respiratory tract infection requiring treatment with antibiotics during the 28 days preceding screening or during the screening period between Visit 1 and Visit 3.
  * History or presence of pulmonary hypertension, respiratory failure, cor pulmonale or right ventricular failure which may impact the safety of the subject in the clinical judgement of the Investigator.
  * History of pulmonary lobectomy, lung volume reduction surgery, or lung transplantation.
  * Use of supplemental oxygen therapy for more than 15 hours per day (includes night-time use).
  * Subjects with hepatic impairment.
  * Subject suffers from any medical condition that would preclude the use of inhaled anticholinergics, including narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or urinary retention.
  * Subjects who are unable to stop any of the following medications, and refrain from their use throughout the study until the final dose of study drug:

    * Short-acting β2 agonists (except study-supplied salbutamol).
    * Short-acting anticholinergic agents (except those used for reversibility testing).
    * Long-acting anticholinergics (except study supplied medication).
    * Combination β2 agonists/anticholinergic agents.
    * Combination β2 agonists/inhaled corticosteroids/anticholinergic agents.
    * Phosphodiesterase 4 inhibitors.
    * Theophyllines.
    * Leukotriene inhibitors.
    * Orally inhaled nedocromil or cromolyn sodium.
    * Oral or parenteral corticosteroids.