E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe 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 demonstrate the superiority of indacaterol (300 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 of treatment. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of indacaterol (300 μg o.d.) compared to placebo on trough Inspiratory Capacity (IC) after 3 weeks of treatment. • To evaluate the effect of indacaterol (300 μg o.d.) compared to placebo on trough FEV1 after 3 weeks of treatment. • To evaluate the effects of indacaterol (300 μg o.d.) compared to placebo on pulmonary function tests after 3 weeks of treatment whilst: 1. The patient is not exercising (i.e. patient is at rest). 2. The patient is exercising. • To evaluate the effect of indacaterol (300 μg o.d.) compared to placebo on exertional dyspnea (Borg CR10 Scale®) during exercise after 3 weeks treatment. • To evaluate the effect of indacaterol (300 μg o.d.) compared to placebo on leg discomfort (Borg CR10 Scale®) during exercise after 3 weeks treatment. • To assess the effect of indacaterol (300 μg o.d.) on patient activity measured using an actigraphy device, as compared with placebo after 3 weeks treatment. |
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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 20 pack years b) Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value. c) Post-bronchodilator FEV1/FVC < 70% |
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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 definition of postmenopausal. 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 oxygen therapy or who experience oxygen desaturation to <80% during cycle exercise on room air 5. Patients with a Wmax value < 20 W at Visit 2 6. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 2. Patients who develop a respiratory tract infection prior to randomization must discontinue from the trial, but may be permitted to re-enroll at a later date 7. Patients with contra-indications of cardiopulmonary exercise testing 8. Patients with concomitant pulmonary disease, pulmonary tuberculosis or clinically significant bronchiectasis 9. Patients with a history of asthma 10. Patients with Type I diabetes. Patients with uncontrolled Type II diabetes signified 11. Patients who, in the judgment of the investigator, 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 12. Any patient with lung cancer or a history of lung cancer 13. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time. 14. Patients with a history of long QT syndrome or whose QTc interval measured at Visit 2 or Visit 4 is prolonged: > 450 ms (males) or > 470 ms (females) as assessed by the investigator. Patients who fail the screening ECG should not be re-screened. 15. 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 16. Patients who do not maintain regular day/night, waking/sleeping cycles 17. Patients who have had treatment with investigational drugs at the time of enrollment, or within 30 days or 5 half-lives prior to Visit 2, whichever is longer. 18. Patients who have had live attenuated vaccinations within 30 days prior to Visit 2 or during the run-in period. 19. 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: • The long acting anti-cholinergic agent tiotropium • Short acting anti-cholinergics • Fixed combinations of β2-agonists and inhaled corticosteroids • Fixed combinations of SABAs plus inhaled anticholinergics • LABAs • SABAs • Theophylline and other xanthines • Parenteral or oral corticosteroids 20. Treatments for COPD and allied conditions: The following medications should not be used unless they have been stabilized: • Cromoglycate, nedocromil, ketotifen, inhaled or nasal corticosteroids and leukotriene • Antihistamines 21. Other excluded medications: • Non-potassium sparing diuretics • Non-selective beta-blocking agents • Cardiac anti-arrhythmics Class Ia, Class III, terfenadine, astemizole, mizolastin. • Tricyclic antidepressants and monoamino-oxidase inhibitors. 22. Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements 23. 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) |
Exercise duration time (in seconds) is measured through constant-load cycle ergometry testing at 75% Wmax (in seconds) after 3 weeks treatment with indacaterol (300 µg o.d.) compared to placebo. The primary variable, exercise duration time (in seconds), is defined as the interval between the onset of imposed constant work rate and the point of symptom limitation at Visit 5 and 8. The baseline measurement is defined as the exercise duration time (in seconds) at Visit 3 and 6.
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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 | 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 | Information not present in EudraCT |
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 | 10 |
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 | 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
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The trial finishes when the last patient finishes the last visit of their second crossover period. |
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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 | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |