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 | 13.1 |
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 compare the rate of serious asthma exacerbations resulting in hospitalization, intubation or death in patients treated with QMF 500/400 μg or MF 400 μg.
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E.2.2 | Secondary objectives of the trial |
• To compare the rate of asthma exacerbations that require systemic corticosteroid use
• To evaluate the safety of QMF versus MF in terms of other adverse events, laboratory values, vital signs and ECG
• To evaluate the benefit of QMF versus MF as measured by spirometry data and ediary data
• To evaluate the effect of QMF on asthma control as measured by the Asthma Control Questionnaire (ACQ) as supportive evidence of treatment efficacy.
Exploratory objectives:
• To explore the impact of QMF on work productivity, as measured by the WPAI-Asthma questionnaire, and on asthma-related medical resource utilization
• To collect utilities (derived from EQ-5D) experienced by patients during the study
• To collect pharmacokinetic data in a subset of the patient population
• To collect pharmacogenetic data in consenting patients*
*Samples will only be collected depending upon regulatory and/or IRB/IEC/REB approval and/or country participation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must give written informed consent before any study related activity is performed Patients below the legal age of consent are required to have the Informed Consent Form signed by the patient’s parent/guardian; adolescents should also sign an assent form
2. Male and female adult and adolescent patients aged ≥12 years (or ≥18 years depending upon regulatory and/or IRB/IEC/REB approval and/or country participation) and ≤ 70 years
3. Patients with a documented diagnosis of persistent asthma (according to GINA guidelines) for a period of at least 6 months prior to Visit 1 and who are currently treated with or qualify for treatment (according to asthma treatment guidelines) with both ICS and LABA combination.
4. Patients demonstrating an increase in FEV1 of ≥12% or ≥200 mLs within 30 minutes after administration of β2-agonist (SABA) as per site protocol. Alternatively, patients may have documentation of reversibility within the last 12 months
5. Patients with an FEV1 ≥50% of predicted normal at Visit 2. This criterion for FEV1 will have to be demonstrated after all restricted medications have been withheld for
appropriate intervals (washout period of at least 6 hours for a short acting β2-agonist and a minimum of 24 hours for a long acting β2-agonist). |
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing (lactating) women confirmed by a positive serum hCG laboratory test (> 5 IU/ml)
2. Women of child-bearing potential (WOCBP), including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal
3. Patients who have smoked or inhaled tobacco products within the 3 month period prior to Visit 2, or who have a smoking history of greater than 10 pack years
4. Patients with a previous diagnosis of COPD
5. Patients who have had a asthma attack/exacerbation requiring hospitalization within 1 month prior to Visit 3
6. Patients who have had an emergency room visit for an asthma attack/asthma exacerbation within 1 month prior to Visit 3
7. Patients who have had a respiratory tract infection or asthma worsening within 1 month prior to Visit 3.
8. Patients who have ever required ventilator support for respiratory failure secondary to asthma
9. Patients with evidence upon visual inspection of clinically significant oropharyngeal candidiasis at baseline or earlier, with or without treatment.
10. Patients with any chronic conditions affecting the respiratory tract or chronic lung diseases which may interfere with the study evaluation or optimal participation in the study
11. Patients with diabetes Type I or uncontrolled diabetes Type II
12. Patients who have a clinically relevant laboratory abnormality or a clinically significant condition that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
13. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time
14. Patients with a history of long QT syndrome or whose QTc interval (Fridericia) measured at Visit 2 or Visit 3 is prolonged: >450 ms as assessed by the central ECG interpretation (Visit 2) or investigator’s interpretation of the pre-dose ECGs (Visit 3). Patients who fail the screening ECG (with the exception of machine failures) should not be re-screened.
15. History of myocardial infarction within the previous 12 months; uncontrolled or unstable angina pectoris or arrhythmia (excluding chronic atrial fibrillation). Known history of congestive heart failure or known LVEF < 45%. Implanted cardiac pacemaker or defibrillator
16. Patients with a history of hypersensitivity to any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
17. Patients who do not maintain regular day/night, waking/sleeping cycles
18. Patients who have had live attenuated vaccinations within 30 days prior to screening visit or during the run-in period.
19. Patients using prohibited medications or patients who cannot adhere to medication washouts.
20. Maintenance Immunotherapy (desensitization) for allergies is allowed if maintenance dose has been administered for at least 3 months prior to Visit 2, and is expected to remain unchanged throughout the course of the study
21. Other excluded medications:
a. Non-potassium sparing diuretics (unless used in combination with potassium
conserving drugs) or with a potassium supplement for which there is adequate
documentation of the subject’s use taken together with a diuretic
b. Non-selective systemic beta-blocking agents
c. Drugs with potential to significantly prolong the QT interval; Cardiac antiarrhythmics
Class Ia (e.g., disopyramide, procainamide, quinidine); Class III (e.g.,
amiodarone, dofetilide, ibutilide, sotalol), the antihistamines astemizole and,
mizolastin, macrolides and antipsychotics (e.g., haloperidol, thioridazine)
d. Tricyclic antidepressants and monoamino-oxidase inhibitors
e. Stong inhibitors of cytochrome P4503A4 (e.g. ketoconazole)
22. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives prior to Visit 2, whichever is longer
23. Patients unable to use a dry powder inhaler device, metered dose inhaler or perform spirometry measurements
24. Patients with a known history of non-compliance to medication or who are unable or unwilling to use Electronic Peak Flow with e-diary device
25. No person directly associated with the administration of the study may participate as a study subject. No family member of the investigational study staff may participate in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety endpoint is the time to the first serious asthma exacerbation during the study. The hazard risk of primary endpoint will be compared between treatment groups. |
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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 | No |
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 | No |
E.8.2.3 | Other | No |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |