E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
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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 assess indacaterol (300 & 600 µg o.d. via SDDPI) superiority in patients with COPD as compared to placebo with respect to 24 h post dose (trough) FEV1 after 12 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
KEY:Effect of indacaterol (300 & 600 µg o.d.) on % ‘days of poor control’ over 52 weeks, versus placebo. Effect of indacaterol versus placebo on the following: St Georges Respiratory Questionnaire, after 12 weeks Time to first COPD exacerbation over 52 weeks QoL after 4, 8, 12, 24, 44 and 52 weeks. COPD exacerbation rates over 52 weeks TDI focal score after 4, 8, 12, 24, 44 and 52 weeks. Trough FEV1 measured on Day 2 and after 52 weeks. Spirometry at all time points with respect to early, peak and trough response. Morning and evening PEF, clinical symptoms and use of rescue medication over 52 weeks. •Long term tolerability and safety (ECG, laboratory tests, blood pressure, and adverse events).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure 2.Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the GOLD Guidelines (2005) and: a)Smoking history of at least 20 pack years b)Post-bronchodilator FEV1 < 80 % and ≥30 %of the predicted normal value c)Post-bronchodilator FEV1/FVC < 70% (Post referes to within 30 min after inhalation of 400 µg of salbutamol
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing women 2. Women of child-bearing potential UNLESS they meet a pre-defined definition of post-menopausal, OR are using one or more pre-specified acceptable methods of contraception: 3. Patients who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 1 or during the run-in period. 4. Patients requiring oxygen therapy for chronic hypoxemia (excluding acute COPD exacerbation). This is typically patients requiring oxygen therapy >15h per day delivered by home oxygen cylinder or concentrator. 5. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. 6. Patients with concomitant pulmonary disease including a history of lung cancer, pulmonary tuberculosis or clinically significant bronchiectasis. 7. Patients with a history (up to and including Visit 1) of asthma indicated by (but not limited to): a) Blood eosinophil count > 400/mm3 b) Onset of symptoms prior to age 40 years. 8. Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or HbA1C > 6.5% of total Hb. 9. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding stable AF), uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the investigator’s opinion might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. 10. Any patient with lung cancer or other active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of the skin is acceptable. 11. Patients with a history of long QT syndrome or whose QTc interval(Bazett’s) measured at Visit 1 or Visit 3 is prolonged to > 450 ms (males) or > 470 ms (females). 12. Patients with a history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof. 13. Patients who do not maintain regular day/night, waking/sleeping cycles 14. Patients who have had treatment with other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 15. Patients who have had live attenuated vaccinations within 30 days prior to Visit 1 and during the run-in period. (Influenza vaccination is acceptable provided it is not administered within 48 h prior to Visits 1, 2 or 3). 16. Treatments for COPD and allied conditions: the following medications must not be used prior to Visit 1 for at least the minimum washout period specified below or at any time during the study: a) The long acting anti-cholinergic agent tiotropium: 7 days b) Short acting anti-cholinergics: 8 h c) Fixed combinations of beta-2-agonists and inhaled corticosteroids: 48 h (Patients taking fixed dose combination therapy must switch to inhaled corticosteroid as monotherapy plus salbutamol/albuterol as rescue therapy) d) Fixed combination of beta-2-agonists and inhaled anticholinergics: 8h e)Long-acting beta-2-agonists: 48 h f) Short acting beta-2-agonists (other than those prescribed in the study): 6 h g) Theophylline and other xanthines: 1 week h) Parenteral or oral corticosteroids: 1 month 17. Treatments for COPD and allied conditions: The following medications should not be used unless they have been stabilized: a) Cromoglycate, nedocromil, ketotifen, inhaled or nasal corticosteroids and leukotriene antagonists - at least one month prior to Visit 1. b) Antihistamines (excluding those in 18c below) - at least 5 days prior to Visit 1. 18. Other excluded medications: a) Non-potassium sparing diuretics (unless administered as a fixed dose combination with a potassium sparing diuretic). b) Beta-blocking agents c) Cardiac anti-arrhythmics Class Ia (e.g., disopyramide, procainamide, quinidine), Class III (e.g., amiodarone, dofetilide, ibutilide, sotalol), terfenadine, astemizole, mizolastin and any drug with potential to significantly prolong the QT interval. d) Tricyclic antidepressants and monoamino-oxidase inhibitors. [Fluoxetine or any other selective serotonin uptake receptor inhibitor may only be permitted if the patient’s treatment regimen has been stable for at least 1 month prior to Visit 2 and they present with a current and historically normal ECG] 19. Patients unable to use a dry powder inhaler device or perform spirometry measurements. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to determine if indacaterol 600 µg is superior to placebo and indacaterol 300 µg is superior to placebo with respect to 24 hour post dose (trough) FEV1 in patients with COPD following 12 weeks of treatment. |
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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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 159 |
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
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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 | 6 |
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 | 6 |