| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic obstructive pulmonary disease (COPD) |
|
| MedDRA Classification |
| 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 (200 & 400 µg o.d. via Certihaler) effectiveness in patients with COPD as compared to placebo with respect to 24 h post dose (trough) FEV1 after 12 weeks of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the effect of indacaterol (200 & 400 µg o.d.) on the following:
1.Number of ‘days of poor control’ over 52 weeks as compared to placebo.
2.To demonstrate non-inferiority of indacaterol versus tiotropium with respect to trough FEV1 following 12 weeks of treatment.
3.Health related quality of life, as compared with placebo
4.Exacerbation rates and time to first exacerbation over 52 weeks as compared with placebo.
5.TDI focal score, as compared with placebo.
6.To compare indacaterol to placebo (superiority) and to tiotropium (non-inferiority) with respect to trough FEV1 on Day 2 and after 52 weeks.
7.Spirometry (FEV1 and FVC) at all time points with respect to the early response, approximate peak response and trough response, compared to placebo.
8.Other clinical variables such as PEF and use of rescue medication as compared to placebo, and
9.To assess the long term tolerability and safety of indacaterol |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| 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 consistent with the GOLD Guidelines (2005) and:
a) Smoking history of at least 20 pack years.
b) Pre-bronchodilator FEV1 at Visit 2 and Visit 3 < 65% of the predicted normal value. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 h during which no short-acting b2-agonist has been inhaled, and 48 h for long-acting b2-agonists.
c) Pre-bronchodilator FEV1 at least 0.75 L and FVC < 70%
|
|
| E.4 | Principal exclusion criteria |
1. Pregnant or nursing women
2. Women of child-bearing potential UNLESS they meet pre-specified definition of post-menopausal OR are using pre-defined acceptable methods of contraception:
3. Patients who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 2 or during the run-in period.
4. Patients requiring long term oxygen therapy for chronic hypoxemia.
5. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 2.
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 Visit 2) 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 with contraindications for tiotropium treatment including symptomatic prostatic hypertrophy, bladder neck obstruction or narrow angle glaucoma.
10. 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, 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.
11. 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.
12. Patients with a history of long QT syndrome or prolonged QTc (Bazett’s) intervals (> 450 ms males; > 470 ms females)
13. 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.
14. Patients who do not maintain regular day/night, waking/sleeping cycles
15. 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
16. Patients who have had live attenuated vaccinations within 30 days prior to Visit 2 and during the run-in period. (Influenza vaccination is acceptable provided it is not administered within 48 h prior to Visits 1 or 2).
17. Treatments for COPD and allied conditions: the following medications must not be used prior to Visit 2 for at least the minimum washout period specified below or at any time during the study:
a) The long acting anti-cholinergic agent tiotropium (other than as prescribed in the study): 7 days
b) Short acting anti-cholinergics: 8 h
c) Fixed combinations of b2-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) Long-acting b2-agonists: 48 h
e) Short acting b2-agonists (other than those prescribed in the study): 6 h
f) Theophylline and other xanthines: 1 month
g) Parenteral or oral corticosteroids: 1 month
18. 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 2.
b) Antihistamines (excluding those in 18c below) - at least 5 days prior to Visit 2.
19. 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]
20. Patients unable to use a dry powder inhaler device or perform spirometry measurements.
21. Patients unable or unwilling to complete a daily diary card.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary objective is to determine if indacaterol (200 & 400 µg o.d.) is superior to placebo with respect to 24 h post dose (trough) FEV1 in patients with COPD following 12 weeks of treatment.
The trough in FEV1 is defined as the average of the 23 h 30 min and the 23 h 55 min values taken in the clinic. at Visits 4 (Day 2), 9 (Week 13) and 17 (Week 53) only. At all other visits the trough in FEV1 is defined as the value taken in the clinic at 5 min prior to dosing.
|
|
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | Yes |
| 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 |
|
| 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
|
| The study treatment period is planned to be 52 weeks with a 14 day run-in period at study start. The study ends on the day of the last patient's last visit. |
|
| 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 | 4 |
| 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 | 4 |
Print
