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 | 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 |
The primary objective of this study is assessing the efficacy of montelukast, a leukotriene receptor antagonist, in adults with mild to moderate persistent asthma. The pharmacological response will be defined as a reduction of  33% of exhaled nitric oxide concentrations over baseline values and/or increase of  15% in pre-bronchodilator FEF25%-75% over baseline values. FEV1, FVC, FEV1/FVC, PEF, FEF25%-75%, MEF75%, MEF50%, MEF25% will also be measured. |
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E.2.2 | Secondary objectives of the trial |
FEV1, FVC, FEV1/FVC, PEF, FEF25%-75%, MEF75%, MEF50%, MEF25%; association between CysLT1 and CysLT2 receptor gene polymorphisms and response to montelukast. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female adults, age 15-70 years, with persistent mild (step 2) or moderate (step 3) asthma based on guidelines for diagnosis and treatment of asthma issued by the National Heart, Lung, and Blood Institute of the National Institute of Health defined on the basis of symptoms more often than twice a week, but less than daily (step 2) or daily without therapy or more often than twice a week, but less than daily with therapy (step 3). 2. Therapy with only short acting 2-agonists administered as needed or drugs for asthma control except leukotriene receptor antagonists. 3. Baseline exhaled nitric oxide concentrations > 20 ppb. 4. Following signs and symptoms of asthma before visit 2: a. asthma symptoms with dyspnea, wheezing, chest tighteness, cough, sputum for at least 12 months. b. Pre-bronchodilator forced expiratory volume in one second (FEV1) > 80% of predicted value after bronchodilator witholding for at least 6 hours at visit 1 and 2. c. Asthma diagnosis defined as: 1) positive reversibility to bronchodilators with increase of 12% in FEV1 or PEF (absolute value), 20-30 minutes after inhalation of a 2-agonist at visit 1; or 2) positive methacholine challenge with a PC20 value  8 mg/ml performed in the previous 12 months; or 3) positive exercise test with a decrease of 15% in FEV1 performed in the previous 12 months. Reversibility test to bronchodilators, methacholine challenge and exercose test will not be repeated if performed in the previous 12 months before visit 1. 5. The person is in good general conditions and is able to complete the study and chew a tablet. 6. Ability to perform reproducible spirometry. 7. Absence of smoking history (including tobacco products) in the previous year. 8. Ability of patient to provide informed consent, as evidenced by signing a copy of the consent form approved by the institutional review board of the subjects respective study institution 9. Women |
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E.4 | Principal exclusion criteria |
1. Person is unable to provide informed consent. 2. Patient is hospitalized. 3. Patient has undergone any major surgical procedure within four weeks of visit 1. 4. Patient has, in addition to asthma, any active, acute or chronic pulmonary disorder documented by history or physical examination. 5. Patient has ever been intubated for asthma, has required acute asthma therapy treated in an emergency room/urgent care facility/office setting within one month or has been hospitalized for asthma within three months of visit 1 or required 2 or more hospitalizations for asthma in the past year. 6. Patient has FEV1 < 60% predicted on visit 1. 7. Patient received 4 or more oral corticosteroid bursts for asthma exacerbations. 8. Patient has unresolved symptoms and signs of an upper respiratory tract infection (URI) within three weeks of visit 1 or during the run-in period. 9. Patient has a history of an anaphylactic allergic reaction related to administration of oral montelukast or the components of tablets. 10. Patient has a clinically significant, active disease of the gastrointestinal, cardiovascular, hepatic, neurological, renal, genitourinary, or hematological systems, or an immunodeficiency, or an autoimmune disorder. 11. Patient has a history of any illness that would require treatment with an excluded medication, could be immediately life threatening, would pose restriction on participation or successful completion of the study, or would pose an additional risk to the patient by administering montelukast. 12. Patient has taken the following medications: 1) Oral, intravenous, intramuscular, intra-articular or inhaled corticosteroids within 4 weeks of visit 1 with the exception of nasal corticosteroids administered on a continuous basis. 2) Leukotriene modifiers within 2 weeks before visit 1. 3) Received treatment within the previous 4 week with medications known to significantly interact with montelukast. 4) Antibiotics for 7 consecutive days in the 4 weeks prior to visit 1. 5) IV gammaglobulin or immunosuppressants within one month of visit 1. 13. Patient has started immunotherapy within six months of visit 1. 14. Patient is unable or unwilling to comply with the study procedures as determined during the run-in period, including compliance with study medication. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Concentrations of exhaled nitric oxide and FEF25%-75% values; assessing a possible association between LTC4 synthase gene polymorphisms and response to montelukast defined as The pharmacological response will be defined as a reduction of  33% of exhaled nitric oxide concentrations over baseline values and/or increase of  15% in pre-bronchodilator FEF25%-75% over baseline values |
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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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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 | 1 |
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 | 1 |