| 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 | 9.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10038738 |
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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 |
| To evaluate safety and efficacy of FF/GW642444 50mcg/25mcg QD and FF/GW642444 100mcg/25mcg QD and FF/GW642444 200mcg/25mcg QD versus GW642444 25mcg QD on the annual rate of moderate and severe exacerbations in subjects with COPD over a 52 week treatment period. This study will evaluate the contribution of the ICS on reducing the rate of exacerbations when used in combination with a fixed dose of the long-acting beta-agonist (LABA) in patients with COPD. |
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| E.2.2 | Secondary objectives of the trial |
| Secondary objectives in this study are to evaluate long term safety and other efficacy assessments and to further investigate any reported cases of pneumonia in subjects with COPD. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the IB/IB supplements and other pertinent documents. 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 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/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.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.Number of pack years = (number of cigarettes per day/20) x number of years smoked Note: Pipe and/or cigar use cannot be used to calculate pack year history. 7.Severity of Disease: Subject with a measured post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 at Screening (Visit 1) Subjects with a measured post-albuterol/salbutamol FEV1 70% of predicted normal values calculated using NHANES III reference equations [Hankinson, 1999] 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 FEV1/FVC ratio and FEV1 percent predicted values will be calculated. 8. History of Exacerbations: A documented history (e.g., medical record verification) of at least one COPD exacerbation in the 12 months prior to Visit 1 that required either oral corticosteroids, antibiotics and/or hospitalization. Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence (color). Subject verbal reports are not acceptable. |
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| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study: 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.α1-antitrypsin deficiency: Subjects with α-1 antitrypsin deficiency as the underlying cause of COPD 4.Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases 5.Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening 6.Chest X-ray: Chest X-ray (posteroanterior with lateral) reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD or another condition that would hinder the ability to detect an infiltrate on CXR (e.g.cardiomegaly, pleural effusion or scarring etc).All subjects will have a chest x-ray at Screening Visit 1 (or historical radiograph obtained within 2 weeks prior to screening) that will be over-read by a central vendor. 7.Risk Factors for Pneumonia: immune suppression (HIV, Lupus, etc) or other risk for pneumonia (e.g.neurological disorders affecting control of the upper airway, such as Parkinson s, Myasthenia Gravis, etc). 8.A moderate and severe COPD exacerbation that has not resolved at least 14 days prior to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if applicable). 9.Pneumonia and/or moderate and severe COPD exacerbation at Visit 1 10.Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled.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. 11.Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled. 12.Hypertension: Subjects with clinically significant hypertension that is uncontrolled 13.Cancer: 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. 14.Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g.beta-agonists, corticosteroid) or components of the inhalation powder (e.g.lactose, magnesium stearate).In addition, patients with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates the subject s participation will also be excluded. 15.15. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years
16. Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol or their ipratropium for the 4-hour period required prior to spirometry testing at each study visit.
17. Additional prohibited medication. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary Efficacy Endpoint Annual rate of moderate and severe exacerbations 6.2.2. Secondary Efficacy Endpoints Time to first moderate or severe exacerbation Annual rate of exacerbations requiring oral corticosteroids Pre-dose FEV1 |
|
| 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.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
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| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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 |
|
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 10 |
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