A 12-week study to evaluate the effect of the drug fluticasone furoate/vilanterol at the dose of 100/25 mcg Inhalation Powder delivered once daily via a Novel Dry Powder Inhaler (NDPI) on arterial stiffness compared with the drug Tiotropium bromide at the dose of 18 mcg delivered once daily via a HandiHaler in subjects with Chronic Obstructive Pulmonary Disease (COPD)
- Conditions
- Subjects with Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 14.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2010-024435-16-IT
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 248
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 A female is eligible to enter and participate in the study if she is of: Non-child bearing potential OR Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods used consistently and correctly 4. Age: >=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 (ATS) /European Respiratory Society(ERS) [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. Tobacco use: Subjects with a current or prior history of >=10 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 7. Severity of Disease: • Subjects with a measured post-albuterol/salbutamol FEV1 <70% of predicted normal values calculated using NHANES III reference equations [Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1). • Subjects with a measured post-albuterol/salbutamol FEV1/FVC ratio of <=0.70 at Screening (Visit 1) [Pelligrino, 2005] 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. 8. Exacerbation History: Subjects who have been hospitalised or have been treated with oral corticosteroids or antibiotics for their COPD within the last 3 years prior to Screening (V1). 9. Baseline aPWV: subjects with a measured aPWV >= 12.0 m/s at Screening (Visit 1).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22
1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study. 2. 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. 3. Other respiratory disorders: The investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. 4. A cardiovascular event: (e.g., Acute Coronary Syndrome, Stroke, Coronary Artery Bypass Surgery, Percutaneous Coronary Intervention) in the 6 months prior to Visit 1. 5. Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1) or having had lung transplantation. 6. Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of â??acute worsening of COPD that is managed by subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician in the 6 weeks prior to Visit 1â?? or â??subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Visit 1â?? 7. Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1. 8. Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, gastrointestinal, neurological, psychiatric, renal, hepatic, immunological, endocrine view protocol for further information. 9. Current severe heart failure (New York Heart Association class IV). Subject will be excluded if they have a known ejection fraction of < 30 %. 10. Hypertension: In the judgment of the investigator the subject does not have uncontrolled hypertension meaning that they are unlikely to require medication adjustments during the study period. 11. Abnormal and clinically significant 12-lead ECG, view protocol for further information. 12. Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years, view protocol for further information. 13. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications and or milk allergies view protocol. 14. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years. 15. Medication prior to spirometry, view protocol for further information. 16. Additional medication: view criterion 16 page 24 of the protocol. 17. Initiation, discontinuation and/or changing dose of medications reported to affect a PWV: Subjects who have started, discontinued and/or are receiving the following medications, view protocol for further information. 18. Oxygen therapy: Supplemental oxygen, with the following exceptions: •ï? Use at high altitude (> 5000 feet) provided subject does not require a flow rate of > 2 L/minute, view protocol for further information. 19. Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program, view protocol for further information. 20. A body mass index (BMI) of >=ï? 35kg/m2 21. Lipid Panel: Subjects with LDL>3.3mmol/L, total cholesterol >5.2mmol/L, and triglycerides >2.24mmol/L (based on Visit 1 fasting lipid panel). 22. Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits. 23. Questionable validity of consent: Su
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to evaluate the effect of FF/VI Inhalation Powder 100/25 mcg administered once daily (QD) compared with Tiotropium 18 mcg QD on arterial stiffness measured as aortic pulse wave velocity (aPWV) in subjects with COPD and aPWV â?¥ 12.0 m/s at baseline.;Secondary Objective: The secondary objectives of the study are to confirm the efficacy of FF/VI Inhalation Powder 100/25 mcg QD compared with Tiotropium 18 mcg QD in improving lung function in subjects with COPD and aPWVâ?¥12.0 m/s at baseline, and to further evaluate the safety in those subjects.;Primary end point(s): The primary endpoint is change from baseline in aortic pulse wave velocity (aPWV) at the end of the 12-week study treatment period. View protocol page 40 for further information.;Timepoint(s) of evaluation of this end point: At week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Other Efficacy Endpoints: â?¢Change from baseline in morning clinic visit trough FEV1 (pre-bronchodilator and pre-dose) at the end of the 12-week study treatment period, â?¢Change from baseline in morning clinic visit trough IC (pre-bronchodilator and pre-dose) at the end of the 12-week study treatment period. Exploratory: â?¢Change from baseline in Central pulse pressure, â?¢Change from baseline in Augmentation Index (AIx), â?¢Change from baseline in Peripheral pulse pressure, â?¢COPD Assessment Test (CAT), â?¢EuroQol Questionnaire (EQ-5D), â?¢St Georgeâ??s Respiratory Questionnaire-C (SGRQ-C), â?¢Healthcare resource utilization Safety: â?¢Incidence of Adverse Events (AEs),â?¢Change from baseline in pulse rate (PR) and mean arterial pressure (MAP) at the end of 12-week treatment period, â?¢Oropharyngeal examination findings at the end of the 12-week treatment period, â?¢Incidence of COPD exacerbations;Timepoint(s) of evaluation of this end point: At week 12