E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate and severe persisitent 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 (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 | No |
E.3 | Principal inclusion criteria |
1.Male and female adults/adolescents aged ≥ 12 years (or ≥ 18 years depending upon reguatory IRB/IEC/REB approval) , who have signed an Informed Consent Form prior to initiation of any study-related procedure. In the case of patients below the legal age of consent, the Informed Consent Form must also be signed by the patient’s 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 (HFA) or equivalent (up to the maximum daily dose as recommended in the package leaflet) for at least one month prior to Visit 1. In addition patients must have been taking a stable dose for at least one month prior to Visit 1. b)Patients whose FEV1 is ≥50% of the predicted normal value for the patient 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 and 48 hours for long acting bronchodilators 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 prior to the evaluation.
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E.4 | Principal exclusion criteria |
-Pregnant or nursing (lactating) women -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/m OR are using one or more of the following acceptable methods of contraception(surgical sterilization, hormonal contraception, double-barrier methods). 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 -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 -Patients who suffer from COPD as diagnosed by the GOLD guidelines (2006). -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. -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 2 must discontinue from the trial, but may be permitted to re-enroll at a later date -Patients with diabetes Type I or those with uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or HbA1C >8.0% measured at Visit 1. -Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically significant condition or a clinically relevant laboratory abnormality such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding stable atrial fibrillation), uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state, that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. -Any patient with active cancer or a history of cancer with less than 5 years disease free survival time. Localized basal cell carcinoma (without metastases) of the skin is acceptable. Patients with a history of cancer and 5 years or more disease free survival time may be included in the study by agreement with Novartis H.Q.personnel on a case-by-case basis. -Patients with a history of long QT syndrome, or whose QTc interval is prolonged to > 450 ms (males) or > 470 ms (females). -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. -Patients who do not maintain regular day/night, waking/sleeping cycles -Patients who have had live attenuated vaccinations within 30 days prior to Visit 1 or during the run-in period. -Patients with a known history of non-compliance to medication or who are unable or unwilling to complete a patient daily diary. -Treatments for asthma and allied conditions: the following medications must not be used prior to Visit 1 for at least the minimum washout period specified below or at any time during the study: a)The long acting anti-cholinergic agent tiotropium (bromide): 7 days. b)Short acting anti-cholinergics: 8 h c)Fixed combinations of 2-agonists and inhaled corticosteroids: 48 h d)Long-acting 2-agonists: 48 h e)Short acting 2-agonists: 6 h f)Theophylline and other xanthines: 7 days g)Parenteral or oral corticosteroids: 3 months. 16.Treatments for asthma: The following medications should not be used unless they have been stabilized for at least one month prior to Visit 1: Cromoglycate, nedocromil, ketotifen, omalizumab, inhaled corticosteroids and leukotriene antagonists. -Other excluded medications: a)Non-potassium sparing diuretics b)All beta-blocking agents c)Cardiac anti-arrhythmics Class Ia, Class III and any drug with potential to significantly prolong the QT interval. d)Tricyclic antidepressants and monoamino-oxidase inhibitors. e)Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives prior to Visit 1, whichever is longer -Patients unable to use a dry powder inhaler device or perform spirometry measurements.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the safety of indacaterol 300 µg and 600 µg o.d. in patients with moderate to severe persistent asthma following 26 weeks of treatment. 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.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 | Yes |
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) | 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 |
additionally double dummy |
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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 | 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.8.5.1 | Number of sites anticipated in the EEA | 70 |
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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date of 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 | |
E.8.9.1 | In the Member State concerned months | |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |