A randomized, multi-center, parallel group, double blind, study to assess the safety of QMF Twisthaler® (500/400µg) and mometasone furoate Twisthaler® (400µg) in adolescent and adult patients with persistent asthma.

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2009-011539-10-HU
• Date of registration: 28/07/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, multi-center, parallel group, double blind, study to assess the safety of QMF Twisthaler® (500/400µg) and mometasone furoate Twisthaler® (400µg) in adolescent and adult patients with persistent asthma.
• Scientific title: A randomized, multi-center, parallel group, double blind, study to assess the safety of QMF Twisthaler® (500/400µg) and mometasone furoate Twisthaler® (400µg) in adolescent and adult patients with persistent asthma.
• Date of first enrolment: 17/09/2009
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011539-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Czech Republic, Hungary

Key inclusion & exclusion criteria

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 ß2-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 ß2-agonist and a minimum of 24 hours for a long acting ß2-agonist).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 interv

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Persistent asthma
MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Name: QMF Twisthaler 500/400µg
Product Code: QMF149
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Indacaterol maleate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: Mometasone furoate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Asmanex Twisthaler 400 micrograms Inhalation Powder
Product Name: MF Twisthaler 400µg
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Mometasone furoate
CAS Number: 83919-23-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

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.

Secondary Objective: • 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

Main Objective: • 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.

Secondary ID(s)

CQMF149A2210

2009-011539-10-CZ