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 | 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 superiority of indacaterol 150 μg o.d. in combination with tiotropium 18 μg o.d. versus tiotropium 18 μg o.d. with respect to standardized AUC for FEV1 between 5 min – 8 h post-dose after 12 weeks of treatment in patients with moderate to severe COPD. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate superiority of indacaterol 150 μg o.d. in combination with tiotropium 18 μg o.d versus tiotropium 18 μg o.d with respect to trough FEV1 24h post-dose after 12 weeks of treatment in patients with moderate to severe COPD. The 24 h post-dose trough FEV1 is defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post-dose.
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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 and over, who have signed an Informed Consent Form prior to initiation of any study-related activities 2.Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the GOLD Guidelines, 2007, Appendix 2) and including: a)Smoking history of at least 10 pack years, both current and ex-smokers are eligible b)Post-bronchodilator FEV1 ≤65% and ≥ 30% of the predicted normal value (Visit 2) c)Post-bronchodilator FEV1/FVC < 70% (Visit 2) (Post refers to 10-15 min after inhalation of 400 µg (4x100µg) of salbutamol, equivalent to 4x90 µg albuterol delivered at the mouthpiece, at 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 post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 mIU/mL or are using one or more of the acceptable methods of contraception. 3.Patients with body mass index (BMI) less than 15 or more than 40 kg/m2 4.Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening (Visit 2). In the event of an exacerbation occurring during the run-in period (Visits 2-4), the patient must discontinue from the study. The patient may be re-screened once the inclusion/exclusion criteria have been met 5.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 6.Patients who have had a respiratory tract infection within 6 weeks prior to Visit 2. Patients who develop a respiratory tract infection between Visit 2 and Visit 4 must discontinue from the trial, but may be re-screened at a later date once the inclusion/exclusion criteria have been met 7.Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), or clinically significant bronchiectasis 8.Patients with a history (up to and including Visit 2) of asthma indicated by (but not limited to): a) onset of respiratory symptoms (such as cough, wheezing, shortness of breath) suggestive of asthma prior to age 40 years b) history of a diagnosis of asthma 9.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 hemoglobin measured at Visit 2 10.Patients with contraindications for tiotropium treatment including medical history of symptomatic prostatic hypertrophy, bladder neck obstruction, narrow angle glaucoma and moderate to severe renal impairment (creatinine clearance ≤ 50 mL/min) 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 investigator or Novartis responsible personnel might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study 12.Patients with lung cancer or a history of lung cancer 13.Patients with active malignancy or a history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. Patients with a history of malignancy 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 Visit 2 is prolonged: >450 ms (males) or >470 ms (females) as assessed by the central ECG interpetation.
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate superiority of indacaterol 150 μg o.d. in combination with tiotropium 18 μg o.d. versus tiotropium 18 μg o.d. with respect to standardized AUC for FEV1 between 5 min – 8 h post-dose after 12 weeks of 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 |
Both arms receive open label tiotropium in combination with blinded indacaterol or placebo. |
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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.8.6 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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |