| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Chronic Obstructive Pulmonary Disease (COPD) |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10038738 |
| E.1.2 | Term | Respiratory, thoracic and mediastinal disorders |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate the 24 hour spirometric effect (FEV1) of Fluticasone Furoate/ Vilanterol Inhalation Powder 100/25mcg once daily compared with Salmeterol/Fluticasone Propionate Inhalation Powder 50/250mcg twice daily over a 12 week treatment period in subjects with COPD. |
|
| E.2.2 | Secondary objectives of the trial |
| A secondary objective of the study is to characterize the time to onset (increase of 100mL above baseline in FEV1) on Treatment Day 1 of both Fluticasone Furoate/Vilanterol Inhalation Powder 100/25 and Salmeterol/Fluticasone Propionate Inhalation Powder 50/250 |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Informed consent: Subjects must give their signed and dated written informed consent to participate 2. Gender: Male or female subjects A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. However in questionable cases, a blood sample with FSH > 40MIU/ml and estradiol <40pg/ml (<140 pmol/L) is confirmatory. OR Child bearing potential, has a negative pregnancy test at screening, and agrees to use one of the contraceptive methods listed in the prococolAge:=>40 years of age at Screening (Visit 1) 4. 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 Agenzia italiana del farmaco - OsSC - Area Promotore Fascicolo 2010-021059-25 18/48 consequences. 5. Severity of Disease: . Subject with a measured post-salbutamol FEV1/FVC ratio of 0.70 at Screening (Visit 1) . Subjects with a measured post-salbutamol FEV1 70% of predicted normal values calculated (via centralized vendor equipment) using NHANES III reference equations at Screening (Visit 1). Post-bronchodilator spirometry will be performed approximately 10-15 minutes after the subject has selfadministered 4 inhalations (i.e., total 400mcg) of 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. 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 |
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| E.4 | Principal exclusion criteria |
| 1.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. Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer,bronchiectasis,sarcoidosis, pulmonary fibrosis, pulmonary hypertension,interstitial lung diseases, or other active pulmonary diseases 3.Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit1)4. 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. Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Screening (Visit 1).6. 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.Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening (Visit 1). 8. Subjects with historical or current evidence of uncontrolled or clinically significant disease such as cardiovascular (i.e., patients requiring ICD or pacemaker requiring a rate set >60 bpm), hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or haematological abnormalities. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. 9.Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis. 10.Subjects with a history of hypersensitivity to any of the study medications (e.g., betaagonists, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the investigator, contraindicates the subject.s participation will also be excluded. 11. Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years 12. Subjects who are medically unable to withhold their salbutamol and/or their ipratropium for the 4-hour period required prior to spirometry testing at each study visit. 13.Use of the following medications within the following time intervals prior to Screening (Visit 1) or during the study:view page 26 of the protocol 14. Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., <=12 hours per day) is not exclusionary.15. Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study. Subjects who are in the maintenance phase of a Pulmonary Rehabilitation Program are not excluded 16. Subjects at risk of non-compliance, or unable to comply with study procedures.Any infirmity, disability, or geographic location that would limit compliance for scheduled visits. 17. Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.18.Women who are pregnant or lactating or are planning on becoming pregnant during the study |
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| E.5 End points |
| E.5.1 | 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 after measurements at 5, 15, 30, and 60 minutes and 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) |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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