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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess indacaterol (200 & 400 µg o.d. via Certihaler) superiority in patients with COPD as compared to placebo with respect to 24 h post dose (trough) FEV1 after 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of indacaterol (200 & 400 µg o.d. via Certihaler) on the following: 1.Number of ‘days of poor control’ reported over the 52 week randomized treatment period, as compared to placebo. 2.Effect on the St Georges Respiratory Questionnaire (SGRQ), as compared with placebo after 12 weeks treatment as compared with placebo 3.Effect on time to first exacerbation during the 52-week randomised treatment period as compared with placebo. For other secondary objectives see protocol. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
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 according to the GOLD Guidelines (2005) and: a) Smoking history of at least 20 pack years b) Pre-bronchodilator FEV1 < 65% of the predicted normal value and at least 0.75 L. This criterion for FEV1 must be demonstrated after a washout period of at least 6 h during which no short-acting b2-agonist has been inhaled, and 48 h for long-acting b2-agonists. c) Pre-bronchodilator FEV1/FVC < 70%
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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 human chorionic gonadotrophin laboratory test (> 5 mIU/mL) 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 (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: a) surgical sterilization (e.g., bilateral tubal ligation, hysterectomy) b) hormonal contraception (implantable, patch, oral) c) double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) 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 (e.g., calendar, ovulation, symptothermal, post-ovulation methods) 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 1 or during the run-in period 4. Patients requiring long term (> 6 months) oxygen therapy for chronic hypoxemia. (‘prn’ use up to 10 h total in any given 24 h period is acceptable) 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 (at least 6 weeks after the start of the respiratory tract infection). 6. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis 7. Patients with a history (up to Visit 1) of asthma indicated by (but not limited to): a) Blood eosinophil count > 400/mm3 b) Onset of respiratory 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 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, 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 (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of the skin is acceptable. Patients with a history of cancer (excluding lung cancer) and 5 years or more disease free survival time may be included in the study by agreement with Novartis Headquarters personnel on a case-by-case basis. 12. Patients with a history of long QT syndrome or whose QTc interval (Bazett’s) is prolonged to > 450 ms (males) or > 470 ms (females) 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 (e.g., night shift workers) 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 1, whichever is longer For remaining exclusion criteria see protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to determine if indacaterol (200 & 400 µg o.d.) is superior to placebo with respect to 24 hour post dose (trough) FEV1 in patients with COPD following 12 weeks of treatment.
The trough in FEV1 is defined as the average of the 23 h 30 min and the 23 h 55 min values taken in the clinic at Visits 4 (Day 2), 9 (Week 13) and 17 (Week 53) only. At all other visits the trough in FEV1 is defined as the value taken in the clinic at 5 minutes prior to dosing.
The baseline measurement is defined as the average of the FEV1 values taken in the clinic at 30 and 5 minutes prior to dosing at Visit 3. The primary variable is ‘trough FEV1’ at Visit 9.
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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 | Yes |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Double dummy, placebo controlled |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 study treatment is planned to last for 52 weeks with a 14-day run-in period at the start of the study. The trial will end on the date of the last patient's last visit. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |