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 | 5.1 |
E.1.2 | Level | llt |
E.1.2 | Classification code | 10003553 |
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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 compare the effect of the two combinations of ciclesonide (320 µg/day) and formoterol (9 µg/day or 18 µg/day) administered once daily in the evening versus monotherapy of formoterol (18 µg od in the evening) on time to first experience of lack of efficacy (LOE)
- to estimate the effect sizes for the comparisons of two combinations of ciclesonide (320 µg/day) and formoterol (9 µg/day or 18 µg/day) administered once daily in the evening versus monotherapy of ciclesonide (320 µg od in the evening) and monotherapy of formoterol (18 µg od in the evening) with regard to 24 h serial measurements of pulmonary function as well as trough FEV1
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E.2.2 | Secondary objectives of the trial |
- the safety and tolerability of 8-week treatment with a fixed combination of ciclesonide and formoterol administered od in the evening in comparison to monotherapy with either formoterol or ciclesonide, e.g. by assessing adverse events, physical exami-nations, ECG and vital signs |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Written informed consent - Male or female outpatients - Age 18 to 75 years - History of bronchial asthma for at least 6 months - Patients, who are in good health with the exception of asthma
Depending on the individual pre-treatment, additionally, one of the following criteria must be met at B0: - In patients pre-treated with 200 - 250 µg fluticasone propionate (or equivalent) per day as monotherapy and at constant dosage during at least four weeks prior to entry into the study, the FEV1 has to be > 60% to < 80% of predicted when rescue medication has been withheld for at least 6 h - In patients pre-treated with 200 - 250 µg fluticasone propionate (or equivalent) per day in combination with one of the following drugs: · an inhaled long-acting ß-agonist (LABA) in a fixed or free ICS combination, or · sustained-release theophylline, or · a leukotriene antagonist, or · a lipoxygenase inhibitor, or · an inhaled anticholinergic, or · an oral ß-agonist, or · inhaled disodium cromoglycate, or · inhaled nedocromil at constant dosage during at least four weeks prior to entry into the study, the FEV1 has to be > 60% to < or = 85% of predicted when rescue medication has been withheld for at least 6 h and asthma controller has been withheld for at least 24 h. |
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E.4 | Principal exclusion criteria |
a) Diseases and health status: · Clinically relevant abnormal laboratory values (e.g. abnormal serum potassium and glucose levels) suggesting an unknown disease and requiring further clinical evaluation, · Concomitant severe diseases or diseases which are contraindications for the use of inhaled corticosteroids (ICS) (e.g. active and inactive pulmonary tuberculosis or relevant fungal, bacterial or viral infections of the lower respiratory tract demanding specific treatment), or contraindications for the use of long-acting beta2-agonists (LABAs, e.g. di-agnosis or history of significant cardiovascular diseases, insulin-dependent diabetes mellitus, uncontrolled hypertension, hyperthyroidism, thyrotoxicosis, phaeochromocytoma, hypokalaemia, prolonged QTc interval (male > 430 ms, female > 450 ms) or tachyarrhythmia), · Suffering from chronic obstructive pulmonary disease (COPD) (i.e. chronic bronchitis or emphysema) and/or other relevant lung diseases causing alternating impairment in pulmonary function (e.g. infection of lower airways within 4 weeks prior to entry into the study), · Current smoking or cessation of smoking within the last 6 months, · Previous smoking with a smoking history > or = 10 cigarette pack-years, · More than one in-patient hospitalization or emergency care visit due to asthma exacerbations in the past year before B0
b) Medications: · Use of injectable corticosteroids or oral systemic corticosteroids within 2 months prior to entry into the study, or more than 3 courses during the last 6 months, · Use of other drugs not allowed and washout times of prohibited drugs cannot be adhered to, · Known or suspected hypersensitivity to ICS, formoterol, lactose monohydrate or to other excipients of the DPI, · Known or suspected hypersensitivity to salbutamol or to excipients of the MDI, · Beginning of immunotherapy within the study period, · Pre-treatment with variable doses of ICS, either as monotherapy or in combination with a non-steroidal controller, during the last 4 weeks prior to entry into baseline period,
c) Common criteria: · Pregnancy or intention to become pregnant during the course of the study, breast feeding, or lack of safe contraception in women of child-bearing potential, · Participation in another study within the 30 days preceding and during the present study, · Previous enrolment into the current study, · Enrolment of the investigator, his/her family members or employees at the investigational site, · Known or suspected non-compliance, alcohol or drug abuse, · Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, · Reversal of sleep pattern (e.g. night shift workers) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Variables of primary interest:
· Time to the first experience of LOE, · Difference in time-averaged AUC (FEV1) over a 24 h dosing interval after 2 weeks of treatment versus the reference profile at visit T0 (based on serial measurements), · Difference in trough FEV1 (more precisely, FEV1 prior to the dose of the 24 h profile, after 2 weeks of treatment compared to FEV1 at the beginning of the 24 h profile at visit T0), |
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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 | 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) | 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 | No |
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.8.6 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 | 7 |
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 | 7 |