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 | 10061877 |
E.1.2 | Term | Obstructive airways disorder |
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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 the effect of 14 days treatment with QVA149 600µg/100µg, QVA149 300µg/100µg, QVA149 150µg/100µg on change in mean 24-h heart rate (ventricular rate) compared to placebo delivered by the Single Dose Dry Powder Inhaler (SDDPI) Concept 1 once a day in patients with moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of 14 days treatment with QVA149 600µg/100µg, 300µg/100µg and 150µg/100µg on change in mean 24-h heart rate (ventricular rate) compared to QAB149 300µg. To evaluate the effect of QVA149 600µg/100µg, 300µg/100µg, 150µg/100µg compared to placebo and QAB149 300µg on: Change in QTc at all time points assessed via ECGs on day 1, day 7 and day 14 (although all time points will be assessed, the main focus will be change in QTc at 30min, 4 h and 23h 45min post dose) 24 hour Holter assessments on day 1 and day 14 in terms of Change in heart rate at 30min, 4 h and 23h 45min hours post dose Number of Ventricular ectopic events including Singular premature ventricular contraction (PVC) Couplets, defined as two PVCs preceded and followed by regular beats Non-sustained Ventricular tachycardia (defined as three or more PVCs and not meeting the definition of sustained ventricular tachycardia) pls see protocol |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure. 2. Patients with moderate to severe stable COPD according to the GOLD Guidelines (2006) (see Appendix 3). 3. Patients who have smoking history of at least 10 pack years. 4. Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal and post-bronchodilator FEV1/FVC <0.70 at Visit 1 and Visit 3. |
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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 urine pregnancy test. 2. Women of child-bearing potential (WOCBP), 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 FSH levels >40 mIU/mL, OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, hysterectomy) hormonal contraception (implantable, patch, oral) double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) (if accepted by local regulatory authority and ethical committee) Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 3. Patients requiring long term oxygen therapy (> 15 hr a day) on a daily basis for chronic hypoxemia, or who have been hospitalized or visited an emergency room for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the screening period (up to Visit 4). 4. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection during the screening period must discontinue from the trial, but will be permitted to re-enroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection). 5. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis. 6. Patients with any history of asthma 7. Patients with blood eosinophil count > 400/mm3 8. 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, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia (excluding stable AF), uncontrolled hypertension, narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. 9. Patients with a history of episodes of cardiac failure, life threatening arrhythmias as seen during screening Holter monitoring and evidence of acute ischemic changes during the screening ECGs 10. Patients with uncontrolled diabetes Type I or 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 Visit 1. 11. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 12. Patients who are contraindicated for or who have shown an untoward reaction to inhaled anticholinergic agents. 13. Patients with a history of long QT syndrome or whose QTc (Fridericia method) interval measured at screening (Visit 1) is prolonged (>450 ms for males or >470 for females). 14. Patients with a history of untoward reactions to sympathomimetic amines, inhaled medication or any component thereof, or any of the study drugs or to drugs with similar chemical structures. 15. Pls see protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the effect of 14 days treatment with QVA 149 600/100 microgrami, QVA 149 300/100 microgrami, QVA 149 150/100 microgrami on change in mean 24-h heart rate (ventricular rate) compared to placebo delivered by the Single Dose Dry Powder Inhaler (SDDPI) Concept 1 once a day in patients with moderate to severe stable Chronic Obstructive Pulomonary Disease (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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.5 | 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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 5 |