| 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 determine if indacaterol (150 µg o.d. and/or 300 µg o.d.) is superior to placebo in terms of 24 h post dose trough FEV1 after 14 days of treatment in each treatment period in patients with COPD. |
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| E.2.2 | Secondary objectives of the trial |
-To determine if indacaterol are at least non-inferior to 18 µg tiotropium in terms of 24 h post-dose trough FEV1 after 14 days of treatment in each treatment period in patients with COPD.
-To evaluate the effects of indacaterol and tiotropium in terms of peak effect and time to peak effect level as determined by FEV1 on Day 1 of treatment in each treatment period.
-To evaluate the area under the FEV1 time curves (0-24 h) on Day 1 and Day 14 in each treatment period
-To evaluate the effects of indacaterol and tiotropium in terms of 24 h post-dose trough FEV1 after 1 day of treatment in each treatment period. Treatment comparison will be made for FEV1 at each scheduled time point.
-To evaluate the safety of indacaterol in terms of vital signs, glucose and potassium, ECG and adverse events.
-To explore the pharmacokinetics of indacaterol after single (on Day 1) and multiple (on Day 14) dose administration.
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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, 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:
a)Smoking history of at least 10 pack years (current or previous smokers)
b)Post-bronchodilator FEV1 < 80% and ≥30% of the predicted normal value.
c)Post-bronchodilator FEV1/FVC < 70%
(‘Post-’ refers to 15-30 min after inhalation of 400 µg of salbutamol at Visit 1)
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| E.4 | Principal exclusion criteria |
1.Pregnant or nursing 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
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 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
3.Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 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 1. Patients who develop a respiratory tract infection between Visit 1 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 of asthma including all patients with:blood eosinophil count > 400/mm3, 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 HbA1C > 8.0 % of total Hb measured at Visit 1
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 unstable ischemic heart disease, arrhythmia , 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
11.Any patient with lung cancer or a history of lung cancer
12.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-by-case basis
13.Patients with a history of long QT syndrome or whose QTc interval (Bazett’s) measured at Visit 1 or Visit 3 is prolonged: > 450 ms (males) or > 470 ms (females) as assessed by the central ECG interpretation (Visit 1) or investigator’s interpretation of the pre-dose ECGs (Visit 3). Patients who fail the screening ECG should not be re-screened.
14.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
15.Patients who do not maintain regular day/night, waking/sleeping cycles
16.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 1, whichever is longer
17.Patients who have had live attenuated vaccinations within 30 days prior to Visit 1 or during the run-in period.
18.Treatments for COPD and allied conditions: the following medications must not be used prior to Visit 1 for at least the minimum washout period specified below or at any time during the study :The long acting anti-cholinergic agent tiotropium, Short acting anti-cholinergics, Fixed combinations of β2-agonists and inhaled corticosteroids, Fixed combinations of a short-acting anti-cholinergic and short acting β2-agonist, Long-acting β2-agonists, Short-acting β2-agonists, Theophylline and other xanthines, Parenteral or oral corticosteroids.
20.Other excluded medications:Non-potassium sparing diuretics, Systemic beta-blocking agents, Cardiac anti-arrhythmics, Tricyclic antidepressants and monoamino-oxidase inhibitors, Cromoglycate, nedocromil, ketotifen and leukotriene antagonists
21.Patients unable to successfully use a dry powder inhaler device, MDI or perform spirometry measurements
22.Patients with a known history of non-compliance to medication or who are unable or unwilling to complete a Patient Diary
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| E.5 End points |
| E.5.1 | Primary end point(s) |
"Primary efficacy variable:
Trough FEV1 after 14 days of treatment in each treatment period for superiority of indacaterol (150 o.d. and 300 µg o.d.) versus placebo."
Therefore, the primary endpoint is the trough FEV1 post Day 14 dose. This is measured on Day 15 in each of the 3 treatment periods. This relates directly to the primary objective of the study.
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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 | 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| 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 | 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
|
| Completion of the study will be when all randomized patients have completed the study or prematurely withdrawn. |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 14 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
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