E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 16.1 |
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 |
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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 |
To demonstrate the superiority of NVA237 50 μg o.d. compared to placebo in addition to background therapy with LABA/ ICS (≥ 800 μg/day of budesonide or equivalent) in terms of trough FEV1 (the mean of values 23h 15min and 23h 45min post dosing) after 26 weeks of treatment in patients with asthma, who are poorly controlled despite treatment with LABA/ICS (≥ 800 μg/day of budesonide or equivalent). |
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E.2.2 | Secondary objectives of the trial |
Key:
Demonstrate superiority of NVA237 50 μg od compared to pbo in addition to background therapy with LABA/ ICS (≥ 800 μg/day of budesonide or equivalent) for:
• Time to 1st moderate or severe asthma exacerbation (52wks treatment)
• ACQ-7 - wk26
Secondary:
Compare efficacy NVA237 50 μg o.d. to pbo in addition to background therapy with LABA/ ICS (≥ 800 μg/day of budesonide or equivalent) for:
• AQLQ(S) - 52wks treatment
• SGRQ - 52wks treatment
• ACQ-7, ACQ-6, ACQ-5 - 52wks treatment
• Peak FEV1, FEV1 AUC0-3h post-dose, and mean pre-dose FEV1 - 52wks treatment
• Trough FEV1 - 52wks treatment
• FEV1 & FVC - individual timepoints
• Morning & evening mean PEF (e-diary)
• Asthma symptoms measured (ACD e-diary)
• Rescue medication (e-diary)
• Rate of moderate/severe asthma exacerbations
• Time to 1st severe asthma exacerbation, and rate of severe asthma exacerbations
• Time to 1st asthma exacerbation of any severity and rate of asthma exacerbations of any severity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent must be obtained before any assessment is performed;
Male and female adult patients aged 18 to <75 years;
Patients with a diagnosis of asthma (according to GINA 2012) for a period of at least 5 years prior screening;
The diagnosis of asthma must have been made before the patient was 40;
Increase in forced expiratory volume in 1 second (FEV1) of ≥ 12% and ≥ 200 mLs within 30 minutes after administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose);
Prebronchodilator FEV1 of ≥ 50 and ≤ 80% of the predicted normal value for the patient;
Patients who qualify for treatment (according to GINA 2012) and have been treated with a stable dose of a fixed dose inhaled corticosteriod (ICS) and long-acting β2 agonist (LABA) combination for at least 4 weeks prior to screening;
Patient must be using a total daily dose of ICS of ≥800 μg/day of budesonide of equivalent;
All patients must be symptomatic with a mean ACQ-5 score ≥ 1.5 at Visit 101 and Visit 102;
A documented history of one or more asthma exacerbations in the previous 12 months that required either treatment with additional or increased dose of systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment, or intubation. |
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E.4 | Principal exclusion criteria |
Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class, or any component thereof: Muscarinic antagonist agents, sympathomimetic amines, lactose or any of the other excipients of the study drug, long and short acting beta-2 agonists, corticosteroids;
Women of child-bearing potential;
Resting QTcF ≥ 450 ms (male) or ≥ 460 ms (female) at Visit 101 (assessed by central reader) and at Visit
102 (assessed by investigator at the site);
Patients with a body mass index (BMI) of more than 40 kg/m2;
Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction, arrhythmia, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment;
Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention (BPH patients who are stable on treatment can be considered);
Patients who have had an asthma exacerbation that required either treatment with additional or increased dose of systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment, or intubation in the 6 weeks prior to screening; Patients who have smoked or inhaled tobacco products within the 6 month period prior to screening, or who have a smoking history of greater than 10 pack years (Note:10 pack years = 1 pack /day x 10 yrs., or ½ pack/day x 20 yrs.);
Patients with a history of chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, and tuberculosis (unless tuberculosis is confirmed as no longer active by imaging);
Patients on Maintenance Immunotherapy (desensitization) for allergies must have been so for at least 3 months prior to run-in, and must be expected to remain unchanged throughout the course of the study; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 26:
Spirometry testing will be performed in accordance with American
Thoracic Society standards. Trough FEV1 defined as the mean of two
measurements at 23 hours 15 minutes and 23 hour 45 minutes post
dosing. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Time to First Moderate or Severe Asthma Exacerbation Over 52 Weeks of Treatment:
Asthma exacerbations are considered to be moderate if treatment with rescue systemic corticosteroids for greater than or equal to 3 days as outpatient or less than or equal to 24 hour emergency room visit was required. Asthma exacerbations are considered severe if treatment with rescue systemic corticosteroids for greater than or equal to 3 days and
hospitalization or emergency department visit greater than 24 hours were required or death due to asthma. The time to the first moderate or severe asthma exacerbation is the study day on which the patient experienced first moderate or severe asthma exacerbation.
For detailed list see full protocol |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 173 |
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 |
Belgium |
Bulgaria |
Canada |
Ireland |
Italy |
Austria |
Croatia |
Netherlands |
Portugal |
Romania |
Slovakia |
Argentina |
Brazil |
Colombia |
Estonia |
Finland |
Germany |
Hungary |
India |
Latvia |
Lithuania |
Spain |
Mexico |
Philippines |
Serbia |
Slovenia |
South Africa |
Turkey |
United Kingdom |
United States |
Vietnam |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 26 |