E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The patients will have mild steroid naïve asthma, that is, patients who suffer from intermitent or persistent mild symptoms of asthma and who have not received inhaled steroids at least within 3 months prior to inclusion. Patients, who are active smokers will be not included in the study, since smoking can affect the values of exhaled NO. Only ex-smokers who have stopped smoking at least 1 year ago will be allowed to participate, if they have a smoking history of less than 10 pack-years. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003555 |
E.1.2 | Term | Asthma bronchial |
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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 |
This study will compare the anti-inflammatory effects of inhaled Budesonide when it is administered 5 minutes after the inhalation of Formoterol (sequential treatment) and when it is given together with Formoterol at the same time. Our hypothesis is that the sequential treatment is more effective in reducing the underlying bronchial inflammation as the simultaneous administration of both drugs. The parameter to measure the reduction of the inflammation will be the fractional exhaled nitric oxide, as a sensitive and non invasive inflammation marker. |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints are other parameters which also quantify indirectly the presence of bronchial inflammation, such as: ·The lung function parameters of FEV1 and FVC. ·eNO concentration at visits 2 to 5. ·Number of eosinophils in induced sputum at screening visit 2 and at visit 6. ·PC30 to methacholine. ·The slope of reduction of eNO.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
·Patients with intermittent or mild persistent asthma, according to the GINA guidelines2. ·Male or female patients 18 years of age or older. ·FEV1 ≥ 80% of predicted value. ·Increased hyper-responsiveness to methacholine with a PC20FEV1 of <4 mg/mL and a PC30FEV1 that leads to a 30% decrease in FEV1 after receiving a maximal concentration of 16 mg/ml methacholine. ·One reversibility test with Salbutamol after a dose of 400 μg ≥ 12% increase FEV1 compared to baseline iwithin the last two years. ·Exhaled NO concentration above 40 ppb. ·Ability to produce sputum after inhalation of hypertonic saline. .Non smoker or ex-smoker with a smoking history of less than 10 pack-years and who have stopped smoking at least 1 year ago. ·Understanding of the study and agreement to give written informed consent before the first study visit.
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E.4 | Principal exclusion criteria |
·Pregnant women, nursing mothers or females with childbearing potential, regardless of whether or not they are sexually active, who do not use a reliable contraceptive method (oral, mechanical, subcutaneous or surgical contraception). ·History of substance abuse or drug abuse within 12 previous months. ·Other respiratory diseases except asthma and allergic rhinitis. ·Use of inhaled within the last 6 weeks or oral/systemic steroids of any kind of corticosteroids in the last 3 months. ·Recent respiratory infection (upper and lower airways) in the last month prior to V0 . ·Asthma exacerbation within 6 weeks prior to inclusion. ·Prophylactic vaccinations against infectious agents within the last 4 weeks. (Flu). ·Treatment with SIT (specific immuntherapy against aeroallergens). ·Clinically significant or uncontrolled cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, autoimmune, neurological or psychiatric disorders that may interfere with successful completion of the study. ·Participation in an investigational drug study within 30 days prior to visit 1 or current participation in another investigational drug study. ·Known sensitivity to the study medication or to any of the excipients contained in any of these formulations. ·Patients who take any other medication for their asthma than beta-2-agonists. ·Patients with a stage 2 hypertension or higher, that is, patients with systolic values iqual or greater than 160 mmHg or diastolic values iqual or greater than 100 mmHg ·Non compliant patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the ratio between the fractional exhaled nitric oxide after 4 treatment days (eNO on visits 5/11) versus the NO concentration at baseline (visit 1/6). |
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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 | No |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | No |
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 | Information not present in EudraCT |
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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A patient will end the trial when he has completed all study visits as specified in 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 | 6 |
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 | 6 |