Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Fluticasone Furoate/GW642444 Inhalation Powder
Product Code: Fluticasone Furoate/GW642444 Inhalation Powder
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Flu
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the IB/IB Supplements and Prescribing Information (tiotropium bromide). Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. Subjects eligible for enrolment in the study must meet all of the following criteria: 1.Type of subject: Outpatient 2.Informed consent: Subjects must give their signed and dated written informed consent to participate. 3.Gender: Male or female subjects Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception. 4.Age: equal or more than 40 years of age at Screening (Visit 1) 5.COPD diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]: COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences. 6.Severity of Disease: •Subject with a measured post-albuterol/salbutamol FEV1/FVC ratio of =0.70 at Screening (Visit 1) [Pelligrino, 2005] •Subjects with a measured post-albuterol/salbutamol FEV1 =30 to =70% of predicted normal values calculated (via centralized vendor equipment) using NHANES III reference equations [Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1). Post-bronchodilator spirometry will be performed approximately 10-15 minutes after the subject has self-administered 4 inhalations (i.e., total 400mcg) of albuterol/salbutamol via an MDI with a valved-holding chamber. The study-provided central spirometry equipment will calculate the FEV1/FVC ratio and FEV1 percent predicted values. 7.Tobacco use: Subjects with a current or prior history of more than10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or cigar use cannot be used to calculate pack-year history. Number of pack years = (number of cigarettes per day/20) x number of years smoked 8.Cardiovascular Disease/Risk Factors: Subjects must have either •A history of diagnosed cardiovascular disease or a prior cardiovascular event including any of the following: •Established (i.e., by clinical signs or imaging studies) coronary artery disease (CAD) •Established (i.e., by clinical signs or imaging studies) peripheral vascular (i.e., arterial) disease (PVD) •Previous stroke •Objectively confirmed TIA (i.e., transient neurological deficit documented by a health-care professional) •Previous Myocardial Infarction (MI) (Note: An MI within 6 months prior to Visit 1 is exclusionary) OR •Presence of one of the following cardiovascular risk fa
Exclusion criteria
Exclusion criteria: 1. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD) 2. Other respiratory disorders: Subjects with 1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases 3. Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1) 4. Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. 5. Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks prior to Screening (Visit 1). 6. Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 6 weeks prior to Screening (Visit 1): Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician. 7. Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening (Visit 1). 8. COPD exacerbation/lower respiratory tract infection during Run-In Period: Subjects who experience a moderate/severe COPD exacerbation (See definitions in Section 6.3.13) and/or a lower respiratory infection (including pneumonia) during the Run-In period. 9. Abnormal clinically significant laboratory finding: Subjects who have an abnormal, clinically significant finding in any liver chemistry, biochemical, or haematology tests at Screening (Visit 1) or upon repeat prior to randomization. 10. Abnormal and clinically significant 12-lead ECG at Screening (Visit 1): Subjects who have an abnormal, clinically significant ECG finding at Screening (Visit 1) or upon repeat prior to randomization. Investigators will be provided with ECG reviews, conducted by a centralized, independent cardiologist, to assist in evaluation of subject eligibility. For this study, an abnormal and clinically significant finding that would preclude a subject from entering the trial is defined as a 12-lead tracing that is interpreted as, but not limited to, the findings listed in Appendix 1 (See Protocol). The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 1 (See Protocol) and determine if the subject is precluded from entering the study (ECG[s] collected prior to randomization). For further exclusion criteria, please refer to the Protocol Section 4.3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy (particularly the change from baseline trough in 24-hour weighted-mean serial FEV1 at the end of a 12-week treatment period) and safety of FF/VI Inhalation Powder 100/25mcg once-daily (QD) via the NDPI compared with tiotropium bromide inhalation powder 18mcg delivered QD via the HandiHaler over a 12-week treatment period in subjects with COPD who have or are at risk for co-morbid cardiovascular disease.;Secondary Objective: Characterize the time to onset (increase of 100mL above baseline in FEV1) on Treatment Day 1 (Visit 2) of both FF/VI Inhalation Powder 100/25 mcg QD and tiotropium bromide inhalation powder 18mcg QD. Evaluate the change from baseline in clinic visit trough FEV1 at Treatment Day 84 (Visit 5) of both FF/VI Inhalation Powder 100/25 mcg QD and tiotropium bromide inhalation powder 18mcg QD.;Primary end point(s): Change from baseline trough in 24-hour weighted-mean serial FEV1 at the end of 12 weeks of treatment on Treatment Day 84 (Visit 5). This weighted mean is calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15 and 30 minutes and 1, 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours on Treatment Day 84 (Visit 5). Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes pre-dose on Treatment Day 1 (Visit 2). ;Timepoint(s) of evaluation of this end point: Treatment Day 84 (Visit 5) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to onset (increase of 100mL above baseline in FEV1) on Treatment Day 1 (Visit 2) Change from baseline in Clinic Visit trough (pre-bronchodilator and pre-dose) FEV1 at Treatment Day 84 (Visit 5) ;Timepoint(s) of evaluation of this end point: Treatment Day 1 (Visit 2) Treatment Day 84 (Visit 5) | — |
Countries
Canada, Czech Republic, Poland, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research and Development Ltd
Outcome results
None listed