Clinical trial NCT01636713 (phase 3, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: gsk573719/vi 62.5/25, gsk573719/vi 125/25, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. Type of subject: outpatient.

          2. Informed Consent: A signed and dated written informed consent prior to study
             participation.

          3. Age: 40 years of age or older at Screening (Visit 1).

          4. Gender: Male or female subjects are eligible to participate in the study.

          5. COPD History: An established clinical history of COPD in accordance with the
             definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]
             as follows:

          6. Tobacco Use and Smoking History: Current or former cigarette smokers with a history of
             cigarette smoking of more than or equal to 10 pack-years

          7. Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a
             post-albuterol/salbutamol FEV1 of less than or equal to 70% of predicted normal values
             calculated using NHANES III reference equations at Visit 1 [Hankinson1999,Hankinson,
             2010].

          8. Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnoea Scale (mMRC)
             at Screening (Visit 2)

        Exclusion Criteria:

          1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
             during the study.

          2. Asthma: A current diagnosis of asthma.

          3. Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung
             infections (such as tuberculosis) and lung cancer are absolute exclusionary
             conditions. A subject, who in the opinion of the investigator has any other
             significant respiratory conditions in addition to COPD should be excluded. Examples
             may include clinically significant, bronchiectasis, pulmonary hypertension,
             sarcoidosis or interstitial lung disease.

          4. Other Diseases/Abnormalities: Subjects with historical or current evidence of
             clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
             immunological, endocrine (including uncontrolled diabetes or thyroid disease) or
             haematological abnormalities that are uncontrolled and/or a previous history of cancer
             in remission for < 5 years prior to Visit 1 (localized carcinoma of the skin that has
             been resected for cure is not exclusionary).

          5. Chest X-Ray: A chest X-ray or computed tomography (CT) scan that reveals evidence of
             clinically significant abnormalities not believed to be due to the presence of COPD. A
             chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available
             within 6 months prior to Visit 1.

          6. Contraindications: A history of allergy or hypersensitivity to any
             anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or
             magnesium stearate or a medical condition such as of narrow-angle glaucoma, prostatic
             hypertrophy or bladder neck obstruction that, in the opinion of the study physician
             contraindicates study participation or use of an inhaled anticholinergic.

          7. Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit
             1.

          8. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior
             to Screening (Visit 1).

          9. 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at
             Visit 1, including the presence of a paced rhythm on a 12-lead electrocardiogram (ECG)
             which causes the underlying rhythm and ECG to be obscured. Investigators will be
             provided with ECG reviews conducted by a centralized independent cardiologist to
             assist in evaluation of subject eligibility.

         10. Screening Labs: Significantly abnormal finding from clinical chemistry and haematology
             tests at Visit 1.

         11. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour
             period required prior to spirometry testing at each study visit.

         12. Medications prior to Screening: List are provided in the protocol

         13. Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed
             for greater than 12 hours a day. As-needed oxygen use (i.e., less than 12 hours per
             day) is not exclusionary.

         14. Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use)
             of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.

         15. Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary
             rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the
             maintenance phase of a pulmonary rehabilitation program are not excluded.

         16. Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2
             years prior to Visit 1.

         17. Affiliation with Investigator Site: Is an investigator, sub-investigator, study
             coordinator, employee of a participating investigator or study site, or immediate
             family member of the aforementioned that is involved in this study.