E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate asthma according to GINA (Global initiative for Asthma, 2004) guidelines. |
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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 assess the effect of Montelukast on the provocative concentration of adenosine-5’-monophosphate (AMP) inducing a 20% decline in Forced Expiratory Volume in one second (FEV1) (referred to as PC20 AMP). |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of Montelukast on recovery time following AMP challenge
To assess the effect of Montelukast on non-invasive inflammatory parameters (nitric oxide measured in exhaled breath; differential cell counts, eosinophil cationic protein, Cys-leukotriens, interleukin-13 and interferon gamma measured in induced sputum and blood; leukotriene E4 measured in urine).
To validate the methodology of AMP challenge as a surrogate marker for the evaluation of the activity of anti-asthmatic drugs |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Eighteen to seventy years old male or female patients having been diagnosed of mild or moderate allergic asthma for at least 6 months. 2. Atopy as indicated by at least one positive skin prick test to one or more common aeroallergens within the last preceding 12 months. 3. Patients must have not been treated with long-acting β2 agonist within the last 48 hours or corticosteroids within 6 weeks prior to study entry. 4. FEV1 ≥ 70% of predicted at screening. 5. PC20 AMP ≤ 400 mg/ml at screening. 6. No smoking history during the last 12 months and no history of smoking more than 10 packs/year (definition: smoking history of 20 cigarettes daily for one year or of 10 cigarettes daily for 2 years etc.). 7. No concurrent treatment, except Salbutamol, may be planned during protocol treatment. 8. Normal organ and marrow function as defined at the discretion of the investigator. 9. Negative pregnancy test in women of reproductive potential. 10. Women of reproductive potential must agree to use adequate contraception prior to study entry and during the trial. 11. Ability to communicate adequately with investigators and comply with the requirements of the entire study. 12. Ability to understand and the willingness to sign an informed consent document.
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E.4 | Principal exclusion criteria |
1. Intubation (ever) or hospitalization for longer than 24 hours within the preceding six weeks for the management of an asthma exacerbation. 2. Asthma exacerbation within 6 weeks prior to study entry. 3. Long-acting β2 agonist within the last 48 hours or corticosteroids within 6 weeks prior to study entry. 4. Respiratory infection within 2 preceding weeks of study entry. 5. Current use of β antagonist. 6. Use of monoclonal antibodies for the treatment of asthma, methotrexate, gold salts, cyclosporine, tacrolimus (topical or systemic), or azathioprine within 3 months prior to study entry. 7. Participation in another investigational drug trial within the preceding 30 days of study entry. 8. History of alcohol or drug abuse. 9. Pregnancy or nursing. 10. HIV seropositivity. 11. Known hypersensitivity against Montelukast-Natrium or any other active ingredient (cellulose, lactose-monohydrate, Hypromellose, Hyprolose, Magnesiumstarate, Titandioxide, Ferrum-III-oxide (E172), Ferrumoxidehydrate (E 172), Carnaubawax). 12. Severe dysfunction of the liver. 13. Hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. 14. Use of Phenobarbital, Phenytoin, Rifampicin. 15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic intracranial disease, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 16. History of severe neurological, cardiovascular, renal, hepatic, respiratory, bone marrow dysfunction, organ graft or autoimmune disease (treated or not).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary activity variable:
The primary activity variable is the provocative concentration of inhaled AMP required to induce a 20% decrease in FEV1 (PC20 AMP), at Day 7 after treatment.
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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 trial is "Last patient last visit" |
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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 |