E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 assess the bronchodilator effect of once-daily indacaterol as a PulmoSphereTM formulation and lactose-blended indacaterol in adult patients with persistent asthma compared with placebo as measured by trough FEV1 after 7-days treatment. |
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E.2.2 | Secondary objectives of the trial |
To assess the bronchodilator effect of once-daily indacaterol pulmosphere formulation/lactose blend in patients with asthma compared with placebo as measured by other measures of lung function
• To assess rescue medication use (Short acting beta agonists (SABA)) over the course of the treatment.
• To assess the safety and tolerability of once-daily indacaterol pulmpsphere/lactose blend in comparison to placebo in terms of the number and percentage of adverse events, laboratory analysis, vital
signs (blood pressure and pulse rate) and ECGs over the course of the treatment.
• To assess the pharmacokinetics of indacaterol following a single dose and after 7 days repeated dosing |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male and female patients with asthma, aged 18 or above, diagnosed according to GINA guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2010) 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 at least 4 weeks prior to screening.
• Patients with an FEV1 at screening and initial baseline of ≥50% 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 washout of 48 hours for a long acting β2-agonist or 7 days for
tiotropium/indacaterol. If appropriate washout has not been achieved when the patient attends for screening the Screening Part 1 assessments should be completed and the patient should return for Screening Part 2.
• Patients who demonstrate an increase of ≥12% and ≥200 mL in FEV1 over their prebronchodilator value after inhaling a total of 400 μg of salbutamol (the reversibility test) as per ATS/ERS Task force: Standardisation of Lung Function Testing guidelines.
Reversibility will have to be demonstrated after an appropriate washout period as described in Section 3.1. The administration of salbutamol for the reversibility test is to be within 30 minutes after pre bronchodilator spirometry. If the patient does not show reversibility this may be repeated once. |
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E.4 | Principal exclusion criteria |
Patients who require the use of ≥ 12 puffs/24 hours of rescue medication for 48 hours between screening and randomization.
• Patients who have a decline in PEFR from the reference PEFR (taken at screening) of ≥30% for 5 of the 6 consecutive scheduled PEFR readings (includes readings taken at morning and evening) between screening and randomization.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use effective contraception during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of the bronchodilator effect of once-daily indacaterol as a PulmoSphere formulation and lactose-blended indacaterol in adult patients with persistent asthma compared with placebo as measured by trough FEV1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 7 days of treatment |
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E.5.2 | Secondary end point(s) |
To assess the bronchodilator effect of once-daily indacaterol pulmosphere forumulation/lactose belnd in patients with asthma
compared with placebo as measured by:
• Peak and time to peak FEV1
• FEV1, Forced Vital Capacity (FVC), FEV1/FVC and forced expiratory flow 25–75% (FEF25-75)
• Standardized FEV1 AUC between baseline (pre-dose) and 4 hr post-dose (AUC0-4h) and
12 hr post-dose (AUC0-12h)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
QAB149 QAB149/Inhalation powder, hard capsule/ 75 mcg |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | No |
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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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |