| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Adult subjects 18 to 75 years of age with persistent asthma |
| Soggetti adulti tra i 18 e i 75 anni con asma persistente. |
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| E.1.1.1 | Medical condition in easily understood language |
| Adults with chronic asthma |
| Adulti con asma cronica. |
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| 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 | 15.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001705 |
| E.1.2 | Term | Allergic asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 adaptive design, dose-ranging study of MK-1029 will assess the dose-related efficacy and safety of MK-1029 compared with placebo using measures of lung function (forced expiratory volume in 1 second (FEV1). The primary objectives are (1) To demonstrate that MK-1029, compared with placebo, results in dose-related improvements in FEV1 over the last 6 weeks of the 12-week active-treatment period; (2) To determine the dose-related safety and tolerability of MK-1029 as monotherapy and as concomitant dosing with monteulkast over 12 weeks. |
| Obiettivo 1: dimostrare che MK-1029, confrontato con placebo, genera miglioramenti dose-correlati nel FEV1 durante le ultime 6 settimane del periodo di trattamento attivo di 12 settimane. Ipotesi 1: MK-1029 è superiore al placebo in una maniera dose-correlata nella variazione media rispetto al basale nel FEV1 durante le ultime 6 settimane del periodo di trattamento attivo di 12 settimane. Obiettivo 2: determinare la sicurezza e la tollerabilità dose-correlata di MK-1029 come monoterapia e come dose combinata con montelukast nell’arco di 12 settimane. |
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| E.2.2 | Secondary objectives of the trial |
| 1)Demonstrate co-administration of MK-1029 & montelukast (ML), compared with ML alone results in FEV1 improvement over last 6 wks treatment; ASSESS: 2)Dose-related efficacy of MK-1029, compared with placebo, on % days with asthma exacerbations, daytime symptom score, as-needed SABA use, night awakening AM & PM PEF over last 6 wks treatment; AQLQ(S) total & each domain scores, ACQ score at wk 12 treatment & asthma attacks over entire treatment. |
| 1.dimostrare che la co-somministrazione di MK-1029 e montelukast, confrontata con montelukast da solo, genera un miglioramento nel FEV1 durante le ultime 6 settimane del periodo di trattamento 2. verificare l’efficacia dose-correlata di MK-1029, confrontato con placebo, sulla percentuale di giorni con esacerbazioni di asma, punteggio dei sintomi diurni,uso di SABA “al bisogno”, risvegli notturni, PEF mattina e pomeriggio durante le ultime 6 settimane del periodo di trattamento; punteggi di dominio totale e individuale dell'AQLQ, punteggio ACQ alla dodicesima settimana di trattamento ed attacchi d'asma per l'intera durata del trattamento. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
OTHER SUBSTUDIES:
A Sputum Substudy will be conducted at selected sites, to analyze sputum of subjects with asthma. The objectives include evaluating the distribution of sputum biomarkers at baseline; Evaluating the..
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ALTRI SOTTOSTUDI:
Studio in doppio cieco,randomizzato,controllato con placebo,multicentrico,a gruppi paralleli,con disegno adattativo,con differenti dosi di MK1029 in soggetti adulti con asma persistente.
v 17/04/2012
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| E.3 | Principal inclusion criteria |
| • Subject is a female or male subject between 18 and 75 years of age • Subject has a consistent clinical history, for at least one year, of symptoms of persistent asthma that may include, but are not limited to, dyspnea, wheezing, chest tightness, cough, and/or sputum production • While withholding SABAs for at least 6 hours and long-acting β- agonists (LABAs) for at least 12 hours, subject has a FEV1 ≥60% and ≤ 85% of the predicted value (≥65% and ≤90% of the predicted value if subject is receiving asthma controller medications) • While withholding SABAs for at least 6 hours and LABAs for at least 12 hours (at Visit 1 only), subject has evidence of reversibility of airway obstruction defined as an increase of FEV1 of 12% or greater, and at least 200 mL, 10 to 30 minutes after SABA administration, documented once during the screening period • Subject's asthma treatment must fall into one of two categories: o The subject must have been using only ''as-needed'' inhaled SABAs (e.g., albuterol/salbutamol) and not using asthma controller medications; OR o The subject must have been receiving stable doses of low- or mediumdose ICS, combination ICS/LABA, and/or other asthma controller medications, including leukotriene receptor antagonists, and can tolerate tapering of these controllers (e.g., ICS) or discontinuing them (e.g., montelukast), during the run-in period • Subject has never smoked or is a non-smoker for at least 1 year, with a smoking history of no more than 10 pack-years • Subject has a Body Mass Index (BMI) between 15 and 40 kg/m2 inclusive (BMI = weight in kg/[height in meters]2 • Subject provides written informed consent for the study. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main study without participating in Future Biomedical Research • Subject has an ACQ-6 of ≥1.5 at the Randomization visit • Subject has a total daytime and nocturnal SABA administration average ≥1 puff per day, as recorded on the subject's e-Diary for the last 7 days prior to Randomization visit |
| 1. Il soggetto è una donna o un uomo tra i 18 e i 75 anni di età. 2. Il soggetto ha un'anamnesi nota, di sintomi di asma persistente, da almeno un anno, che possono includere, ma non limitarsi a dispnea, respiro sibilante, senso di restringimento del torace, tosse e/o produzione di espettorato. 3. Mentre sospende i SABA per almeno 6 ore e i β-agonisti ad azione prolungata (LABA) per almeno 12 ore, il soggetto presenta un FEV1 ≥ 60% e ≤ 85% del valore predetto (≥ 65% e ≤ 90% del valore predetto se il soggetto sta ricevendo farmaci per il controllo dell’asma2). 4. Mentre sospende i SABA per almeno 6 ore e i LABA per almeno 12 ore (solo alla Visita 1), il soggetto presenta evidenza di reversibilità dell’ostruzione delle vie respiratorie definita come un aumento del FEV1 uguale al 12% o maggiore, e almeno di 200 ml, da 10 a 30 minuti dopo la somministrazione di SABA, documentata una volta durante la Visita 1, la Visita 2 o la Visita 3. 5. Il trattamento dell’asma del soggetto deve rientrare in una delle due categorie di seguito descritte: 7.1 il soggetto deve aver usato solo SABA inalati “al bisogno” (per esempio, albuterolo/salbutamolo) e non farmaci per il controllo dell’asma; OPPURE 7.2 il soggetto deve aver ricevuto dosi stabili di ICS a dose bassa o media, ICS/LABA combinati e/o altri farmaci per il controllo dell’asma, inclusi gli antagonisti del recettore del leucotriene, e può tollerare la diminuzione della somministrazione di questi farmaci di controllo (per esempio, ICS) o la loro interruzione (per esempio, montelukast), durante il periodo di run-in. |
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| E.4 | Principal exclusion criteria |
| incapacitated preventing informed consent from being obtained, unable to read or comprehend written material, or unable to comply with the study procedures or protocol • Subject has a recent history (≤3 months) of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia prior to Visit 1• Subject is hospitalized or has been hospitalized in the 4 weeks prior to Visit 1 • Subject has undergone any major surgical procedure within the 4 weeks prior to Visit 1 • Subject has evidence of another clinically significant, active pulmonary disorder such as bronchiectasis or chronic obstructive pulmonary disease (COPD) documented by history, physical examination, or chest x-ray • Subject has been treated in an emergency room for asthma within the 4 weeks prior to Visit 1 or has been hospitalized for asthma within the 8 weeks prior to Visit 1 • Subject has had a respiratory tract infection which necessitated treatment with antibiotics within the 8 weeks prior to Visit 1 • Subject has evidence of active, clinically significant sinus disease within 1 week prior to Visit 1 • Subject is hypersensitive to inhaled β-agonists, leukotriene antagonists, leukotriene synthesis inhibitors, or any of their formulation components • Subject has evidence of uncontrolled hypertension, defined as systolic >160 mmHg and/or diastolic >100 mmHg, during at least 2 of the first 3 study visits • The electrocardiogram (ECG) obtained at Visit 1 demonstrates clinically significant or unexplained abnormality, that may include but is not limited to: a clinically significant conduction disturbance (e.g., second or third degree AV block), clinically significant tachycardia, active cardiac ischemia, or a QTc > 460 msec • Subject has used any medication with a narrow therapeutic index (e.g., warfarin, coumadin, dicoumarol, digoxin, digitoxin) within the 2 weeks prior to Visit 1 or plans to take such medications during the study • Subject is unable to comply with the study procedures or protocol, including completion of the e-Diary and compliance with study medication • Subject experiences a clinically significant worsening of their asthma between Visits 1 and 3. |
| 1 . Il soggetto ha un’anamnesi recente (≤ 3 mesi) di infarto miocardico, insufficienza cardiaca congestizia o aritmia cardiaca non controllata prima della Visita 1. 2 . Il soggetto è ospedalizzato o è stato ospedalizzato nelle 4 settimane precedenti la Visita 1. 3 . Il soggetto è stato sottoposto a procedure chirurgiche di rilievo entro le 4 settimane precedenti la Visita 1. 4 . Il soggetto ha partecipato a uno studio clinico con un farmaco sperimentale entro le 4 settimane precedenti la Visita 1. 5 . Il soggetto presenta evidenza di un altro disturbo polmonare attivo clinicamente significativo come la bronchiectasia o broncopneumopatia cronica ostruttiva (BPCO) documentata da anamnesi, esame obiettivo o radiografia del torace. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint for this study is the average change from baseline in FEV1 over the last 6 weeks of the 12-week active treatment period. |
| L’endpoint primario di efficacia per questo studio è la variazione media dal basale della FEV 1 nel corso delle ultime 6 settimane del periodo di trattamento attivo di 12 settimane. E.5.1.1 Le ultime 6 settimane del periodo di trattamento attivo di 12 settimane( settimana 8, 10 e 12). |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The last 6 weeks of the 12-week active treatment period ( weeks 8, 10, and 12). |
| La variazione media dal basale nel FEV1 durante le ultime 6 settimane del periodo di trattamento attivo di 12 settimane sarà stimata da questo modello. |
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| E.5.2 | Secondary end point(s) |
| • percentage of days with asthma exacerbations • daytime symptom score • as-needed SABA use • nocturnal awakenings • AM and PM PEF • Asthma Quality of Life Questionnaire with Standardised Activities [AQLQ(S)] total and individual domain scores • Asthma Control Questionnaire-6 (ACQ-6) score • asthma attacks |
| • percentuale di giorni con esacerbazioni di asma • punteggio dei sintomi diurni • uso di SABA “al bisogno” • risvegli notturni • PEF mattina e pomeriggio • punteggi di dominio totale e individuale del Questionario sulla qualità della vita correlata all’asma con attività standardizzate [AQLQ(S)] • punteggio del Questionario sul controllo dell’asma 6 (ACQ-6) • attacchi di asma |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The various time points include daily or every 2 weeks of the 12-week active treatment period; Week 12 of the 12-week active period and over the entire 12-week active treatment period. |
| I vari intervalli di tempo comprendono tutti i giorni o ogni 2 settimane del periodo di trattamento attivo di 12 settimane; la settimana 12 del periodo attivo di 12 settimane e per l'intero periodo di 12 settimane di trattamento attivo. |
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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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| 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 | 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 8 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 75 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Japan |
| United States |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 39 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 39 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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