E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COPD (chronic obstructive pulmonary disease) |
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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 |
•Evening dosing of indacaterol versus placebo: To assess the efficacy of indacaterol 300 µg o.d. when dosed in the evening compared to placebo in patients with moderate to severe COPD, as assessed by trough FEV1 at 23 h 10 min and 23 h 45 min post dose taken on Day 14. |
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E.2.2 | Secondary objectives of the trial |
•Safety:To assess the safety of indacaterol 300 µg dosed in the evening with regard to ECGs, laboratory tests, blood pressure, heart rate, and adverse events. •Morning and evening dosing of indacaterol versus placebo after 14 days treatment: To compare descriptively trough FEV1 of indacaterol 300 µg o.d. when dosed in the morning versus placebo with trough FEV1 when dosed in the evening versus placebo in patients with moderate to severe COPD.
Exploratory objectives : - Comparisons versus placebo of trough FEV1 for indacaterol 300 µg o.d. (evening dosing), indacaterol 300 µg o.d. (morning dosing), and FEV1 for salmeterol 50 µg bid after 14 days of treatment. All treatment contrasts not already covered by the primary and secondary comparisons will be evaluated. see other exploratory objectives in the protocol page 7-8. |
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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% (Post-bronchodilator refers to approximately 15-30 min after inhalation of 400 µg of salbutamol)
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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 Follicle Stimulating Hormone levels > 40 mIU/mL or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization , hormonal contraception, and double-barrier methods. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 3.Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the period between Visit 2 and Visit 3. 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 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 . 7.Patients with concomitant pulmonary disease, pulmonary tuberculosis or clinically significant bronchiectasis 8.Patients with a history of asthma 9.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 2. 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 measured at Visit 2 or Visit 3 is prolonged: > 450 ms (males) or > 470 ms (females) as assessed by the central ECG interpretation or investigator’s interpretation of the pre-dose ECGs. 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 investigational drugs at the time of enrollment, or within 30 days or 5 half-lives prior to Visit 2, whichever is longer. 17.Patients who have been vaccinated with attenuated vaccines within 30 days prior to Visit 2 or during the run-in period. 18.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 b2-agonists and inhaled corticosteroids •Fixed combinations of a short acting β2-agonist (SABA) plus inhaled anticholinergic •LABAs •SABAs •Theophylline and other xanthines •Parenteral or oral corticosteroids 19.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 antagonists •Antihistamines 20.Other excluded medications: •Non-potassium sparing diuretics •Systemic beta-blocking agents •Cardiac anti-arrhythmics Class Ia, Class III, and any other drug with potential to significantly prolong the QT interval. •Tricyclic antidepressants and monoamino-oxidase inhibitors. 21.Patients unable to successfully use a single or multiple dose dry powder inhaler device 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) |
This study is designed to demonstrate that dosing in the evening is effective, providing full 24h bronchodilation.
The primary variables (trough FEV1) are the mean of spirometry (FEV1) measurements at two time points observed at the end of the dosing period, namely at 23h10mn and 23h45mn post evening dose of day 14 of each treatment period. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Health-related Quality of Life |
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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 |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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
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Completion of the study will be when all randomized patients have completed the study or prematurely withdrawn. |
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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 | 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 |