E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 evaluate the bronchodilator effect of three different indacaterol dosing regimens (once-daily/q.d., alternate day/q.o.d. and twice daily/b.i.d.) on trough FEV1 after two-weeks of treatment in patients with persistent asthma. • To assess the bronchodilator effect of q.d. and b.i.d. indacaterol dosing regimens on Standardized* FEV1 AUC(0-24h). • To assess the bronchodilator effect of q.o.d and q.d. indacaterol dosing regimens on Standardized* FEV1 AUC(0-48h) and FEV1 AUC(24-48h).
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E.2.2 | Secondary objectives of the trial |
• To assess FEV1 and FVC at each post-dose time-point on Days 1/2 and Days 16/17/18/19 (q.d. and b.i.d. treatment). • To assess FEV1 and FVC at each post-dose time-point on Days 123 and Days 15/16/17/18/19 (q.o.d. treatment). • Peak FEV1 on Day 1 and 16. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female adult patients aged 18 years or above who have signed an Informed Consent Form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to the first study visit. 2. Patients with persistent asthma, diagnosed according to GINA guidelines 2008 and who additionally meet the following criteria: • Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the package leaflet, in a stable regimen for the month prior to first study visit. • Patients with an FEV1 at screening of ≥50% and ≤90% of the predicted normal value for the patient. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 hours during which no short acting β2-agonist has been inhaled, and a minimum of 48 hours for a long acting β2-agonist and 7 days for tiotropium. • Patients who demonstrate an increase of ≥12% and ≥200 mL in FEV1 over their pre-bronchodilator value within 30 minutes after inhaling a total of 400 μg/360 μg of salbutamol/albuterol MDI (or equivalent dose of DPI) (the reversibility test). Reversibility will have to be demonstrated after an appropriate washout period as described above. The administration of salbutamol/albuterol for the reversibility test is to be within 30 minutes after pre bronchodilator spirometry. Reversibility has to be demonstrated at screening or between screening and pre-dose Day 1, in order for patients to be included in the trial. 3. Females patients may be included but must comply with the following in order to be included: • Women of child-bearing potential (WOCBP) (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) may be included providing they are using two effective methods of contraception (for example oral contraceptive and condom).. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Note: Reliable contraception must be maintained throughout the study. • Postmenopausal women may be included providing they meet the following criteria: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 IU/L assessed at screening, • Sterilized women may be included if they have undergone surgical bilateral oophorectomy with or without hysterectomy at least 6-months previously. 4. BMI must be within the range 18-40 kg/m2 (inclusive). 5. Vital signs (after 3 minutes resting measured in the supine position) not considered by the Investigator to be indicative of a disorder which would make it unsafe for subject to participate in the study or require medical intervention. 6. Able to communicate well with the investigator and comply with the requirements of the study. 7. Male subjects must be using two highly effective methods of contraception, (comprising a barrier method condom or occlusive cap plus spermicide) plus ensure use by the female partner of a second method of contraception. These measures should be in place for the entire duration of the study up the Study Completion visit, and males should refrain from fathering a child in the three (3) months following the last study drug administration.
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E.4 | Principal exclusion criteria |
1. Patients who have a smoking history of greater than 10 pack years, (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked). Current smokers who smoke greater than 10 cigarettes per day. Smokers should maintain their usual smoking habits throughout the course of the study. 2. Patients who have had previous intubation for a severe asthma attack/exacerbation. 3. Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to the first study visit. 4. Patients who have had an emergency room visit for an asthma attack/exacerbation within 6 weeks prior to the first study visit or any time between the first study visit and pre-dose Day 1. 5. Patients who have had a lower respiratory tract infection within 6 weeks prior to the first study visit or any time between the first study visit and pre-dose Day 1. 6. Patients with seasonal allergy whose asthma is likely to deteriorate during the study period. 7. Patients who require the use of ≥8 inhalations per day of the short-acting β2-agonist (100 µg/90 µg salbutamol/albuterol MDI or equivalent dose of DPI) on any 2 consecutive days from screening to randomization. 8. Patients diagnosed with COPD as defined by the (GOLD Guidelines, 2009). 9. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest X-ray to be no longer active) or clinically significant bronchiectasis. 10. Any patient with lung cancer or a history of lung cancer. (...) 29. Patients with a history of hypersensitivity or allergy to indacaterol or other similar drugs in its class or to the excipients (including lactose) of the drug product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The primary endpoint is a change from baseline in trough FEV1 (48 hours after the final alternate day/q.o.d. dose: 24 hours after the final once daily/q.d. dose: 12 hours after the evening twice daily/b.i.d. dose). • To assess the bronchodilator effect of q.d. and b.i.d. indacaterol dosing regimens on Standardized FEV1 AUC(0-24h). • To assess the bronchodilator effect of q.o.d. and q.d. indacaterol dosing regimens on Standardized FEV1 AUC(0-48h) and FEV1 AUC(24-48h).
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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 | Yes |
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 |
tolerability; to evaluate 3 different dose regimens |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 |
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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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please refer to the protocol |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |