E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COPD (chronic obstructive pulmonary disease) |
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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 | 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 demonstrate the superiority of indacaterol (150 μg o.d.) versus salmeterol (50 μg b.i.d.) with respect to standardized area under the curve (AUC) for forced expiratory volume in one second (FEV1) between 5 min and 11 h 45 min after the morning dose on day 84 of treatment in patients with moderate to severe COPD. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the superiority of indacaterol (150 μg o.d.) versus salmeterol (50 μg b.i.d.) with respect to trough FEV1 after 84 days of treatment in both arms: Trough refers to the mean of FEV1 at 23:10 and 23:45h after the morning dose of indacaterol, and the mean of FEV1 at 11:10 and 11:45h after the anticipated time of the evening dose of salmeterol. To compare spirometry for indacaterol (150 μg o.d.) with salmeterol (50 μg b.i.d.). To evaluate the effect of indacaterol 150 μg o.d. compared with salmeterol 50 μg b.i.d. in respect to TDI focal score on Day 84. To compare the relative safety of indacaterol (150 μg o.d.) versus salmeterol (50 μg b.i.d) with respect to ECGs, laboratory tests, blood pressure, heart rate, and adverse events. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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, 2007, Appendix 2) and additionally including: • Smoking history of at least 10 pack years • Post-bronchodilator FEV1 <80% and ≥30% of the predicted normal value at screening (Visit 2). • Post-bronchodilator FEV1/FVC < 70% at screening (Visit 2) |
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL) 2. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL or are using one or more of the acceptable methods of contraception define in the protocol. 3. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation; 4. Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening. In the event of an exacerbation occurring during the run-in period, the patient must discontinue from the study. The patient may re-enroll once the inclusion/exclusion criteria have been met 5. Patients whose body mass index is less than 15 or greater than 40 kg/m2; 6. Patients requiring oxygen therapy for chronic hypoxemia (excluding acute COPD exacerbation). This is typically patients requiring oxygen therapy >15 h per day delivered by home oxygen cylinder or concentrator 7. Patients who have had a respiratory tract infection within 6 weeks prior to screening. Patients who develop a respiratory tract infection between prescreening and randomizationmust discontinue from the trial, but may be permitted to re-enroll at a later date once the inclusion/exclusion criteria have been met 8. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis 9. Patients with a history of asthma indicated 10. 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 > 8.0 % of total Hb measured at screening 11. 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 chronic stable atrial fibrillation) or other clinically significant ECG findings, uncontrolled hypertension and other significant cardiac disease or conduction defect, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the opinion of the investigator or Novartis responsible personnel might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study 12. Any patient with lung cancer or a history of lung cancer 13. Any patient with 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. Patients with a history of cancer (excluding lung cancer) and 5 years or more disease-free survival time may only be included in the study by agreement with Novartis Headquarters personnel on a case-by-case basis 14. Patients with a history (or family history) of long QT syndrome or whose QTc interval (Fridericia) measured at screening is prolonged: >450 ms (males) or >470 ms (females) as assessed by the central ECG interpretation. Patients who; - fail the screening ECG (with the exception of machine failures) should not be rescreened; - fail the baseline site assessed ECG and considered clinically significant by the investigator 15. Patients with a history of hypersensitivity to any of the study drugs or to drugs with similar classification, including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof 16. Patients who do not maintain regular day/night, waking/sleeping cycles 17. Patients who have had treatment with investigational drugs at the time of enrollment, or within 30 days or 5 half-lives prior to screening whichever is longer 18. Patients who have had live attenuated vaccinations within 30 days prior to the screening visit or during the run-in period. 19. Patients receiving any prohibited medications listed in protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate superiority of indacaterol (150 μg o.d.) versus salmeterol (50 μg b.i.d.) in respect to standardized area under the curve (AUC) for forced expiratory volume (FEV1) between 5 min and 11 h 45 min after the morning doses after 84 days treatment in patients with moderate to severe COPD. |
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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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 82 |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |