revefenacin in chinese subjects with moderate to very severe chronic obstructive pulmonary disease(copd)

Conditions: COPD

Summary: 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.

Keywords: revefenacin long-acting muscarinic receptor antagonist(lama)