E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 demonstrate the superiority of indacaterol (150 μg o.d.) in patients with moderate to severe COPD as compared to placebo with respect to exercise endurance time (measured through constant-load cycle ergometry testing) after 3 weeks treatment. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of indacaterol (150 μg o.d.) compared to placebo on trough (i.e. 24h post dose) Inspiratory Capacity (IC) after 3 weeks of treatment 2. To evaluate the effect of indacaterol (150 μg o.d.) compared to placebo on trough (i.e. 24h post dose) FEV1 after 3 weeks of treatment 3. To evaluate the effects of indacaterol (150 μg o.d.) compared to placebo on pulmonary function tests after 3 weeks of treatment whilst: • The patient is not exercising (i.e. the patient is at rest) • The patient is exercising 4. To evaluate the effect of indacaterol (150 μg o.d.) compared to placebo on exertional dyspnea (Borg CR10 Scale®) during exercise after 3 weeks treatment. 5. To evaluate the effect of indacaterol (150 μg o.d.) compared to placebo on leg discomfort (Borg CR10 Scale®) during exercise after 3 weeks treatment 6. To assess the effect of indacaterol (150 μg o.d.) on patient activity measured using an actigraphy device, as compared with placebo after 3 weeks treatment |
|
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, 2007), Appendix 3 of the protocol and additionally including: a. Smoking history of at least 10 pack years. b. Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value at screening. c. Post-bronchodilator FEV1/FVC < 70% at screening. |
|
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 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 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 (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). 3. Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment and/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, the patient must discontinue from the study. The patient may re-enroll once the inclusion/exclusion criteria have been met. 4. Patients whose body mass index is less than 15 or greater than 40 kg/m2. 5. Patients requiring oxygen therapy for chronic hypoxemia (excluding acute COPD exacerbation). This is typically patients requiring oxygen therapy more than 15 h per day delivered by home oxygen cylinder or concentrator. 6. Patients with a Wmax value < 20 W (as determined by the incremental cycle endurance test) at Visit 2 7. Patients who have had a respiratory tract infection within 6 weeks prior to screening (Visit 2). Patients who develop a respiratory tract infection between prescreening (Visit 1) and randomization (Visit 3) must discontinue from the trial, but may be permitted to re-enroll at a later date once inclusion/exclusion criteria have been met (at least 6 weeks after the start of the respiratory tract infection) 8. Patients with contra-indications of cardiopulmonary exercise testing as described in the protocol. 9. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis. 10. Patients with a history of asthma indicated by (but not limited to): - onset of respiratory symptoms suggestive of asthma prior to age 40 years - a history of a diagnosis of asthma 11. Patients with Type I diabetes or uncontrolled Type II diabetes including patients with a history of blood glucose levels consistently outside the normal range or HbA1C > 8.0% of total Hb measured at screening (Visit 2) 12. 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) those described in the protocol. 13. Any patient with lung cancer or a history of lung cancer 14. Any patient with 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). 15. Patients with a history (or family history) of long QT syndrome or whose QTc interval (Fridericia’s) measured at screening (Visit 2) is prolonged: > 450 ms (males) or > 470 ms (females) as assessed by the investigator. 16. Patients who have had live attenuated vaccinations within 30 days prior to screening visit (Visit 2) or during the run-in period. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate the superiority of indacaterol (150 μg o.d.) in patients with moderate to severe COPD as compared to placebo with respect to exercise endurance time (measured through constant-load cycle ergometry testing) after 3 weeks treatment. |
|
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 | 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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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
| |
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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |