E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intermittend or mild asthma according to the definition of the Global Initiative ofor Asthma (GINA) guidelines step 1 or step 2 (2004) |
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MedDRA Classification |
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 investigate the effects of addition of Montelukast (Singulair™ 10 mg o.d.) to regular treatment (14 days) with the long-acting beta-agonist Salmeterol (Serevent™ 50µg b.i.d.) in patients with intermittent or mild asthma on:
development of tolerance to bronchoprotection against methacholine-induced bronchoconstric-tion achieved by 50 µg salmeterol DPI
development of tolerance to bronchodilation (acute reversal of methacholine-induced broncho-constriction) achieved by 400µg salbutamol MDI
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E.2.2 | Secondary objectives of the trial |
to investigate the effects of addition of Montelukast (Singulair™ 10 mg o.d.) to regular treatment (14 days) with the long-acting beta-agonist Salmeterol (Serevent™ 50µg b.i.d.) in patients with intermittent or mild asthma on:
correlation of breath condensate and induced sputum airway cys-LT concentrations and devel-opment of tolerance to beta-agonists in asthmatic subjects.
Cys-LT concentrations in EBC after montelukast vs. placebo
Exhaled nitric oxide levels after montelukast vs. placebo |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
intermittent or mild persistent asthmatics (GINA step 1 and 2, GINA 2004) positive skin test to more or equal to 1 allergen within the last 12 months prior to screening or at screening visit PC20 methacholine below or equal to 4 mg/ml at screening FEV1 >85% pred Asthma medication: only short-acting beta-agonists prn written informed consent patients who, with the exception of asthma, are in good health clinical stable asthma
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E.4 | Principal exclusion criteria |
asthma severity > step 2 GINA history of lower or upper airway infection in the last 4 weeks prior to screening diagnosis of chronic obstructive pulmonary disease (COPD) and/or other relevant lung dis-eases (e. g. history of bronchiectasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease and active tuberculosis) current smoker and ex-smokers with more than 10 pack years* (* 1 pack year is defined as 20 cigarettes/day for 1 year.) clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (assessed by the investigator) suspected hypersensitivity and / or contraindication to any ingredients of the study medication and / or the rescue medication use of prohibited medication prior to screening and throughout the study wash-out times of drugs defined in protocol cannot be adhered to alcohol and / or drug abuse pregnancy, breast feeding women of childbearing potential need to practice a safe contraception during the entire course of the study participation in another clinical trial within 30 days preceding the screening visit patients not able to follow study procedures (e.g. language problems, psychological disorders) suspected non-compliance known hypersensitivity to Montelukast, SereventTM Diskus, or Salbutamol MDI or any of the ingredients
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E.5 End points |
E.5.1 | Primary end point(s) |
Protection afforded by a single dose of 50µg Salmeterol against methacholine-induced bronchocon-striction after 14 days of regular treatment with Salmeterol (50 µg bid) alone or in combination with Montelukast. This will be measured (a) as the post-Salmeterol PC20 methacholine (mg/ml) on day 14 in treatment period (TP) A vs TP B, and (b) as the degree of tolerance expressed as relative change in post-Salmeterol PC20 methacholine (doubling concentrations) from day 1 to day 14 dur-ing TP A vs TP B. Co-primary endpoint This will be the acute rescue bronchodilator effect of 400µg salbutamol measured as (a) % change and (b) AUC of FEV1 5, 10, 15, 30, and 45 minutes after methacholine-induced bronchoconstric-tion on day 14 during TP A vs TP B
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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 | Yes |
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 | 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 | No |
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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End of the trial is defined as the last visit of the last patient included into the trial, no interims analysis is planned. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |