A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Cavosonstat Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Exclusion Criteria

• •Patients meeting any of the following criteria must be excluded from the study (full details in main text):
• •* Patients with other respiratory disorders: current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, uncontrolled or unstable sleep apnea, cor pulmonale, clinically significant pulmonary hypertension or other active pulmonary diseases
• •* Chest X-ray (or computerized tomography \[CT\] scan) reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD
• •* Moderate or severe AECOPD within the previous four weeks
• •* An upper or lower respiratory tract infection that required the use of antibiotics within the previous four weeks
• •* Long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for more than 12 hours a day
• •* Oral therapies for COPD (e.g. oral steroids, theophylline and roflumilast) or antibiotics or oral corticosteroid therapy within four weeks prior to screening
• •* Prior history of, or planned pneumonectomy or lung volume reduction surgery
• •* Participation in the acute phase of a pulmonary rehabilitation program within four weeks of screening or planned during the study
• •* History of malignancy of any organ system within five years, except skin cancer which has been stable over one year and the investigator believes is no clinical significance.
• •* Patients with uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant. This includes any hepatic disease or moderate to severe renal impairment.
• •* Documented clinically significant cardiovascular disease such as: any history of arrhythmias, angina, recent (\<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months prior to Screening.
• •* Known or suspected history of alcohol or drug abuse within the last 5 years. Positive urine drug screen and blood alcohol level screen.
• •* Clinically significant abnormal values for laboratory safety tests (hematology, blood chemistry, viral serology or urinalysis) at Screening, as determined by the Investigator.
• •* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than twice the upper limit of normal.
• •* Received an experimental drug within 30 days or five half-lives, whichever is longer.
• •* Women who are pregnant or breast-feeding.
• •* Prior exposure to a GSNOR inhibitor.
• •* Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
• •* A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
• •* Any other reason that the Investigator considers makes the patient unsuitable to participate.