| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| moderate to severe COPD (Chronic Obstructive Pulmonary disease) |
|
| 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 |
|
| 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 determine if indacaterol (150 and/or 300 μg) is superior to placebo in terms of FEV1 at 5 mins post-dose. |
|
| E.2.2 | Secondary objectives of the trial |
- To compare the effects of indacaterol (150 and 300 μg) versus salmeterol/fluticasone (50/500 μg) in terms of FEV1 at 5 mins post-dose.
- To compare the effects of indacaterol (150 and 300 μg) versus salbutamol (200 μg) in terms of FEV1 at 5 mins post-dose.
- To compare the effects of salmeterol/fluticasone (50/500 μg) and salbutamol (200 μg) versus placebo in terms FEV1 at 5 mins post-dose.
- To evaluate the effects of indacaterol (150 and/or 300 μg), salmeterol/fluticasone (50/500 μg), salbutamol (200 μg) and placebo in terms of:
• Proportion of patients with at least 10, 12 and 15% increase in FEV1 from period baseline at 5, 15 and 30 mins, and 1 and 2 h post-dose
• Proportion of patients with at least 12% and 200 mL increase in FEV1 from period baseline at 5, 15 and 30 mins, and 1 and 2 h post-dose
• FEV1 at 15 and 30 mins, and 1 and 2 h post-dose
- To compare the effects of indacaterol 150 μg versus indacaterol 300 μg in terms of FEV1 at 5 mins post-dose. |
|
| 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, 2006) and:
d) Smoking history of at least 20 pack years
e) Post-bronchodilator FEV1 <80% and ≥30% of the predicted normal value.
f) Post-bronchodilator FEV1/FVC < 70% (‘Post-’ refers to 15-30 mins after inhalation of 400 μg of salbutamol at Visit 2) |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or nursing (lactating) women
2. Women of child-bearing potential, 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 following acceptable methods of contraception:
• surgical sterilization
• hormonal contraception
• double-barrier methods
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 and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation
3. Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 2 or during the run-in period
4. Patients requiring long-term oxygen therapy (>15 h a day) for chronic hypoxemia.
5. 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 3 must discontinue from the trial, but may be permitted to re-enroll at a later date
6. Patients with concomitant pulmonary disease, pulmonary tuberculosis or clinically significant bronchiectasis
7. Patients with a history (up to and including Visit 2) of asthma indicated by at least one of the following:
a) blood eosinophil count >400/mm3
b) onset of asthma 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 glycosylated hemoglobin (HbA1c) >8.0% of total hemoglobin measured at Visit 2
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 a history of lung cancer
11. Any patient with active cancer or a history of cancer with less than 5 years disease-free survival time. Localized basal cell carcinoma of the skin is acceptable. Patients with a history of 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-bycase basis
12. Patients with a history of long QT syndrome or whose QTc interval (Bazett’s) measured at Visit 2 or Visit 3 is prolonged: >450 ms (males) or >470 ms (females) as assessed by the central ECG interpretation (Visit 2) or investigator’s interpretation of the pre-dose ECGs (Visit 3). Patients who fail the screening ECG (with the exception of machine failures) should not be re-screened
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 prior to Visit 2, whichever is longer
16. Patients who have been vaccinated with live attenuated vaccines within 30 days prior to Visit 2 or during the run-in period.
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 anticholinergic agent tiotropium
b) Short acting anticholinergics
c) Fixed combinations of β2-agonists and inhaled corticosteroids
d) Fixed combinations of an anticholinergic and short acting β2-agonist
e) Long-acting β2-agonists
f) Short-acting β2-agonists
g) Theophylline and other xanthines
h) Parenteral or oral corticosteroids
18. The following medications should not be used unless they have been stabilized:
a) Inhaled or nasal corticosteroids
b) Antihistamines
19. Other excluded medications:
a) Non-potassium sparing diuretics
b) Systemic non-selective beta-blocking agents
c) Cardiac anti-arrhythmics Class Ia and Class III , terfenadine, astemizole,
mizolastin and any other drug with potential to significantly prolong the QT interval.
d) Tricyclic antidepressants and monoamino-oxidase inhibitors.
e) Cromoglycate, nedocromil, ketotifen and leukotriene antagonists |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is to determine if indacaterol (150 and/or 300 µg) is superior to placebo in terms of FEV1 at 5 mins post-dose in patients with COPD. |
|
| 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 | No |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
| |
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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