| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 |
| 1) to compare breath patterns of organic volatile compounds detected detected by biosensors in healthy and asthmatic subjects; 2) to compare breath analysis with biosensors with measuremenet of exhaled nitric oxide, an independent noninvasive method for assessing lung inflammation; 3) to investigate the effect of montelukast (Singulair) and fluticasone (Flixotide) on breath patterns detected by biosensors in adults with stable mild persistent asthma. |
| 1) confrontare l analisi del pattern di composti organici volatili nel respiro effettuata mediante biosensori in adulti sani e con asma; 2) confrontare l analisi del respiro mediante biosensori con la misurazione del monossido di azoto nell aria espirata, una metodica indipendente per la valutazione non invasiva dell infiammazione polmonare; 3) valutare effetto di montelukast (Singulair) e fluticasone (Flixotide) sul profilo di risposta rilevato dai biosensori in adulti con asma stabile di grado lieve. |
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| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Male or females adults, aged 15 to 70 years, have atopic mild persistent asthma at step 2 of the Guidelines for the Diagnosis and Management of Asthma issued by the National Heart, Lung, and Blood Institute of the National Institute of Health as defined by a history of symptoms more than twice a week but less than daily (step 2). 2. Current asthma treatment includes short-acting inhaled -agonist alone as needed. 3. Positive skin prick testing. 4. Patient fulfills all the following signs and symptoms of asthma by visit 2: a) History of symptoms including, but not limited to dyspnea, wheezing, chest tightness, cough, or sputum production for at least 12 months. b) A forced expiratory volume in one second (FEV1) of at least 80% of the predicted value (pre-bronchodilator) while withholding -agonist for at least six hours. This must be demonstrated twice at visits 1 and 2. c) Patient has a diagnosis of asthma as defined by 1) an increase in FEV1 or PEF of ≥12% (absolute value), 20 to 30 minutes after inhaled -agonist administration at visits 1, OR 2) a positive methacholine PC20 (provocative concentration causing a 20% fall in FEV1) of 8 mg/ml or lower which was performed within the previous 12 months, OR 3) a fall in FEV1 of at least 15% after an exercise challenge which was performed within the previous 12 months. -agonist reversibility and the methacholine and exercise challenge tests may be satisfied within the previous 12 months if there is adequate source documentation. 5. Patient is able to chew a tablet and inhale drug from a dry powder inhaler. 6. Patient is judged to be in good, stable physical and mental health (except for his/her asthma) based on the medical history, physical examination, and routine laboratory data, and appears able to successfully complete this trial. 7. Ability to perform reproducible spirometry. 8. Nonsmoker including no use of smokeless tobacco products in the past year. 9. Ability of parent to provide informed consent, as evidenced by signing a copy of the consent form approved by the institutional review board of the subject s respective study institution, with assent from the child. 10. Women give up pregnancy throughout the study duration (5 weeks). - atopic non asmatic patients |
| 1. 1. Adulti di sesso maschile e femminile atopici, di eta` compresa tra 15 e 70 anni con asma di grado lieve persistente (step 2) secondo le linee guida per la diagnosi e la terapia dell asma del National Heart, Lung, and Blood Institute of the National Institute of Health definito sulla base di una storia di sintomi che si presentano > 2 volte a settimana ma meno di una volta la giorno (step 2). 2. Terapia con soli 2-agonisti a breve durata di azione somministrati al bisogno. 3. Prove cutanee positive per uno o piu` allergeni inalatori. 4. Presenza dei seguenti segni e sintomi di asma precedentemente alla visita 2: a. sintomatologia asmatica con dispnea, respiro sibilante, senso di costrizione toracica, tosse, espettorato da almeno 12 mesi. b. Volume espiratorio forzato in un secondo (FEV1) superiore a 80% del valore teorico (prima del broncodilatatore) dopo che la somministrazione del -agonista e` stata sospesa da almeno 6 h. Questo deve essere dimostrato due volte alla visita 1 e 2. c. La diagnosi di asma e` definita da: 1) test di reversibilita` al broncodilatatore, con aumento del FEV1 o del PEF 12% (valore assoluto), 20-30 minuti dopo la somministrazione di un -agonista, alla visita 1, o 2) test alla metacolina positivo con un valore di PC20 (concentrazione che provoca una riduzione del FEV1 del 20%)  8 mg/ml che sia stato eseguito nei 12 mesi precedenti, o 3) diminuzione del FEV1 15% dopo test da sforzo eseguito nei 12 mesi precedenti. Test di reversibilita` al broncodilatatore, test alla metacolina e spirometria sotto sforzo non saranno ripetuti se eseguito entro 12 mesi dalla visita 1. 5. La persona e` in grado di masticare una compressa e di inalare il farmaco da dispositivi inalatori. 6. La persona e` in buone condizioni psico-fisiche, tranne che per la presenza di asma, sulla base di anamnesi, esame obiettivo e test di laboratorio ed e` in grado di completare lo studio. 7. Possibilita` di eseguire una spirometria in modo riproducibile. 8. Assenza di storia di fumo compresi prodotti del tabacco non da fumo nell ultimo anno. 9. Possibilita` di fornire il consenso informato mediante firma del modulo di informazione per il paziente approvato dal Comitato Etico. 10. Donne in eta` fertile che si impegnano a non iniziare una gravidanza durante tutta la durata dello studi (5 settimane). - adulti sani di sesso maschile e femminile non atopici, di eta` compresa tra 15-70 anni |
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| E.4 | Principal exclusion criteria |
| 1. Patient is, in the opinion of the investigator, mentally or legally incapacitated preventing informed consent from being obtained, or cannot read or comprehend written material. 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 < 80% predicted on visit 1, nighttime awakenings from asthma 2 or more times per week, or PEF variability of 30% or more. 7. Patient received 4 or more oral corticosteroid bursts for asthma exacerbations in the past year. 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 either a marketed or investigational drug or is otherwise hypersensitive to inhaled -agonist or oral montelukast or inhaled fluticasone or their components. 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 the study drugs. 12. Patient has taken the following medications: a) 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. b) Leukotriene modifiers, theophylline derivatives, or mast cell stabilizers for asthma within 2 weeks before visit 1. c) Received treatment within the previous 4 week with medications known to significantly interact with montelukast. d) Antibiotics for 7 consecutive days in the 4 weeks prior to visit 1. e) 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. |
| 1.1. Persone che non sono in grado di fornire il consenso informato. 2. Pazienti ricoverati in ospedale. 3. Pazienti che abbiano subito un intervento chirurgico nelle 4 settimane precedenti la visita 1. 4. Presenza di patologie polmonari acute o croniche, oltre ad asma, evidenziate dall anamnesi o esame obiettivo. 5. Pazienti che siano stati intubati per asma, abbiano richiesto terapia per attacco acuto di asma nel mese precedente l inizio dello studio (visita 1) o siano stati ricoverati per asma nei tre mesi precedenti la visita 1 o siano stati ricoverati per asma due o piu` volte nell anno precedente. 6. Pazienti con FEV1 < 80% del valore teorico in una spirometria eseguita alla visita 1, sintomi di asma notturna due o piu` volte alla settimana o variabilita` del PEF  30%. 7. Quattro o piu` periodi di terapia con glucocorticoidi per riacutizzazioni di asma nell anno precedente. 8. Infezioni delle vie respiratorie superiori nelle tre settimane precedenti la visita 1. 9. Storia di allergia a farmaci o ipersensibilita` a -agonisti o montelukast o fluticasone o eccipienti presenti nella formulazione farmaceutica. 10. Patologie gastrointestinali, cardiovascolari, epatiche, neurologiche, renali, genitourinarie, ematologiche, endocrine, oftalmiche, articolari, sindromi da immunodeficienza o malattie autoimmunitarie, malattie dell apparato locomotore. 11. Pazienti con storia di malattie per cui sia richiesta terapia con un farmaco la cui somministrazione non e` consentita nel presente studio, malattie che possano costituire un pericolo immediato o compromettano la partecipazione od il completamento dello studio, o aumentino il rischio per il paziente a causa della somministrazione di montelukast o fluticasone. 12. Pazienti che abbiano preso i seguenti farmaci: a) glucocorticoidi per os, endovena, intramuscolo, intra-articolari o inalatori nelle 4 settimane precedenti la visita 1 con l eccezione degli steroidi intranasali somministrati cronicamente. b) antagonisti dei leucotrieni, teofillina e derivati, cromoni nelle due settimane precedenti la visita 1. c) terapia con farmaci che presentano significative interazioni con montelukast nelle 4 settimane precedenti la visita 1. d) antibiotici per > 7 giorni consecutivi nelle 4 settimane precedenti la visita 1. e) gammaglobuline per via endovenosa o farmaci immunosoppressori nel mese precedente la visita 1. 13. Pazienti che hanno iniziato la immunoterapia nei 6 mesi precedenti la visita 1. 14. I pazienti non sono in grado o non vogliono seguire le procedure dello studio compresa la compliance con la terapia con montelukast o fluticasone. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Concentrations of exhaled nitric oxide |
| misura del monossido dell'aria espirata frequenze rivelate dai biosensori spirometria |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | No |
| 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
| |
| 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 | 0 |
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