E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe persistent asthma |
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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 | 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 safety of indacaterol 300 and 600 µg o.d over 26 weeks, in patients with moderate to severe persistent asthma who are receiving background therapy with inhaled corticosteroid. The assessment of safety will include all safety measurements including adverse events and asthma exacerbations however, particular attention will be paid to the key safety variables for this class of drug namely serum potassium and glucose, heart rate, blood pressure, and QTc. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of indacaterol (300 and 600 µg o.d.) on pulmonary function assessments (trough FEV1, and FVC) over 26 weeks. To evaluate the effect of indacaterol (300 and 600 µg o.d.) on asthma exacerbation rates over 26 weeks. To characterize long term exposure and PK to indacaterol (300 and 600 µg o.d.) using sparse sampling and application of a population PK and PK/PD model in order to analyze the effects of age, gender and race on PK variables. |
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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 patients aged ≥ 12 years who have signed an Informed Consent form prior to initiation of any study-related procedure. In the case of patients below the legal parent/guardian. 2. Patients with moderate to severe persistent asthma, diagnosed according to GINA guidelines (Updated 2006) and who additionally meet the following criteria: a) Patients who have used treatment with a bronchodilator, either regularly or on-demand, and who have used a daily dose of at least 100 µg BDP or equivalent dose of an alternative ICS (up to the maximum daily dose as recommended in the package leaflet) for at least one month prior to Visit 1. The ICS dose must have been stable during this period and must be expected to remain stable throughout the study. b) Patients whose FEV1 is ≥50% of the predicted normal value for the patient, allowing for race correction if appropriate, at both Visit 1 and Visit 2. This criterion for FEV1 is to be demonstrated after an appropriate washout period for all bronchodilators (e.g. at least six hours for short-acting bronchodilators such as albuterol and 48 hours for long acting bronchodilators such as salmeterol and formoterol) prior to the evaluation. c) Patients with documented (in the previous 6 months) or who demonstrate (prior to visit 2) a ≥12% and at least 200 ml increase in FEV1, over their pre-bronchodilator value within 30 minutes after inhaling a total of 200/180 µg salbutamol/albuterol (i.e. two inhalations), demonstrated after an appropriate washout period for all bronchodilators (e.g. at least six hours for short-acting bronchodilators such as albuterol and 48 hours for long acting bronchodilators such as salmeterol and formoterol) prior to the evaluation. |
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E.4 | Principal exclusion criteria |
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 hCG laboratory test (> 5 IU/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 postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m OR are using one or more of the following acceptable methods of contraception a) surgical sterilization (e.g., bilateral tubal ligation) 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). For females aged 12 to 17 years acceptable methods of contraception may include total abstinence at the discretion of the investigator. 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 used tobacco products within the 12 month period prior to Visit 1, or 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). 4. Patients who suffer from COPD as diagnosed by the GOLD guidelines (2006). 5. Patients who have had emergency room treatment for an acute asthma attack in the 6 weeks prior to Visit 1 or who have been hospitalized for an acute asthma attack in the 6 months prior to Visit 1, or at any time between Visit 1 and Visit 2. 6. Patients who have had a respiratory tract infection within 6-weeks prior to Visit 1. PLS SEE PROTOCOL |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the long term safety of indacaterol 300 & 600 μg o.d compared with salmeterol over 52 weeks, in patients with persistent asthma who are receiving background therapy with inhaled corticosteroid and are provided with a short acting β2 agonist as rescue medication prn. The assessment of safety will include all safety variables however, particular attention will be paid to the key safety parameters for this class of drug namely, serum potassium, blood glucose, heart rate, blood pressure, QTc, lung function assessments (FEV1 and FVC), adverse events and asthma exacerbations. |
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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 | 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 | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |