Safety and Efficacy of Mometasone Furoate Delivered Via Concept1 Device or Twisthaler® Device in Adult and Adolescent Patients With Persistent Asthma

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy, safety and pharmacokinetics of Mometasone furoate delivered via Concept1 device or Twisthaler® device in adult and adolescent patients with persistent asthma.

Official Title
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A Randomized, Double-blind, Double-dummy, 4-week Treatment, Parallel-group Study to Evaluate the Efficacy and Safety of Two Doses of Mometasone Furoate Delivered Via Concept1 or Twisthaler® in Adult and Adolescent Patients With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Mometasone furoate
* Device: Concept 1
* Device: Twisthaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females who were ≥ 12 years old at the time informed consent was obtained Patients with persistent asthma, diagnosed according to GINA 2010 guideline and who additionally met the following criteria Patients who were receiving ICS treatment up to the maximum dose per day as indicated in the corresponding package leaflet and also a stable ICS regimen for at least 4 weeks prior to screening (Visit 2). Patients whose level of asthma control according to GINA 2010 guideline was Partly Controlled or Uncontrolled at screening (Visit 2). Patients with a pre-bronchodilator FEV1 value of ≤ 80% of predicted normal value at screening (Visit 2). Patients who demonstrated an increase of ≥ 12% and 200 mL in FEV1 over prebronchodilator value within 30 minutes after inhalation of 400 μg of salbutamol (360 μg of albuterol) at Visit 2 or between Visit 2 and Visit 5. Patients who were confirmed as ICS sensitive by ACQ-5 and FEV1 at Visit 5. Key exclusion criteria included: Patients diagnosed with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease, updated 2010. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest X-ray to be no longer active), or clinically significant bronchiectasis. Patients with any chronic conditions affecting the respiratory tract (e.g., chronic sinusitis) or chronic lung diseases, which in the opinion of the investigator may interfere with the study evaluation or optimal participation in the study. Patients with seasonal allergy which is likely to deteriorate his/her asthma condition during the study period judged by the investigator. Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1 or any time between Visit 1 and Visit 5 must discontinue from the trial (screening failure). Patients who have had an emergency room visit for an asthma attack/exacerbation within 4 weeks prior to Visit 1 or any time between Visit 1 and Visit 5 must discontinue from the trial (screening failure). Patients who have ever required intubation for a severe asthma attack/exacerbation. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1, or any time between Visit 1 and Visit 5 must discontinue from the trial (screening failure). Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mometasone furoate 80 μg<br>Description: Mometasone furoate (MF) 800 ug delivered via the Twisthaler® device for 2 weeks, followed by MF 200 ug delivered via the Twisthaler® device for 2 weeks or no treatment for 2 weeks, then randomized to MF 80 ug delivered via the Concept1 device for 4 weeks. | Drug: Mometasone furoate<br>* Mometasone furoate (MF) 80 µg once daily delivered via Concept1 device; MF 200 μg once daily delivered via Concept1 device; MF 320μg once daily delivered via Twisthaler® device or 800 μg once daily delivered via Twisthaler® device<br>* Other names: QMF149;Device: Concept 1<br>* A single dose dry powder inhaler (SDDPI)<br>|
| Experimental: Mometasone furoate 200 µg<br>Mometasone furoate (MF) 800 ug delivered via the Twisthaler® device for 2 weeks, followed by MF 200 ug delivered via the Twisthaler® device for 2 weeks or no treatment for 2 weeks, then randomized to MF 200 ug delivered via the Twisthaler® device for 4 weeks. | Drug: Mometasone furoate<br>* Mometasone furoate (MF) 80 µg once daily delivered via Concept1 device; MF 200 μg once daily delivered via Concept1 device; MF 320μg once daily delivered via Twisthaler® device or 800 μg once daily delivered via Twisthaler® device<br>* Other names: QMF149;Device: Twisthaler<br>* A single dose dry powder inhaler (SDDPI)<br>|
| Experimental: Mometasone furoate 320 µg<br>Mometasone furoate (MF) 800 ug delivered via the Twisthaler® device for 2 weeks, followed by MF 200 ug delivered via the Twisthaler® device for 2 weeks or no treatment for 2 weeks, then randomized to MF 320 ug delivered via the Concept1 device for 4 weeks. | Drug: Mometasone furoate<br>* Mometasone furoate (MF) 80 µg once daily delivered via Concept1 device; MF 200 μg once daily delivered via Concept1 device; MF 320μg once daily delivered via Twisthaler® device or 800 μg once daily delivered via Twisthaler® device<br>* Other names: QMF149;Device: Concept 1<br>* A single dose dry powder inhaler (SDDPI)<br>|
| Experimental: Mometasone furoate 800 µg<br>Mometasone furoate (MF) 800 ug delivered via the Twisthaler® device for 2 weeks, followed by MF 200 ug delivered via the Twisthaler® device for 2 weeks or no treatment for 2 weeks, then randomized to MF 800 ug delivered via the Twisthaler® device for 4 weeks. | Drug: Mometasone furoate<br>* Mometasone furoate (MF) 80 µg once daily delivered via Concept1 device; MF 200 μg once daily delivered via Concept1 device; MF 320μg once daily delivered via Twisthaler® device or 800 μg once daily delivered via Twisthaler® device<br>* Other names: QMF149;Device: Twisthaler<br>* A single dose dry powder inhaler (SDDPI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Measurements were taken on day 29 after treatment. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) After Days 8, 15 and 22 of Treatment | Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Measurements were taken on days 8, 15 and 22 after treatment. Data within 6 hr of rescue medication use is excluded from this analysis. | Days 8, 15 and 22 | 
| Forced Vital Capacity (FVC) at All Time Points | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data within 6 hr of rescue medication use is excluded from this analysis. Mixed model: FVC = treatment + gender+ baseline FVC + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region. | Days 1, 8, 15, 22, 28 and 29 at all time points | 
| Forced Expiratory Flow Between 25% and 75% (FEF25-75%) at All Time Points | The Forced Expiratory Flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. | Days 1, 8, 15, 22, 28 and 29 at all time points | 
| Forced Expiratory Volume in 1 Second Forced Vital Capacity (FEV1/FVC) Percent at All Time Points | Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) was measured via spirometry conducted according to internationally accepted standards. Data within 6 hr of rescue medication use is excluded from this analysis. | Days 1, 8, 15, 22, 28 and 29 at all time points | 
| Change From Baseline in Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over 4 Weeks of Treatment | Peak expiratory flow rate (PEFR) was measured via electronice Peak flow meter by patient at home. Mixed model used: change from baseline in the mean evening PEFR = treatment + age + gender + baseline evening PEFR + level of asthma control + region + center (region)+ error. Center is included as a random effect nested within region. | Baseline and week 4 | 
| Change From Baseline in Asthma Control Questionnaire (ACQ-5) by Visit | Asthma symptoms were evaluated by the Asthma Control Questionnaire (ACQ). The ACQ-5 has five questions of the asthma symptoms to be answered by the patient. The overall score is the average of the 5 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma. A negative change in score indicates improvement in symptoms. MIXED model: Change from baseline in ACQ-5 = treatment + gender + baseline ACQ-5 score + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region. - Baseline ACQ-5 is defined as the questionnaire completed on Day 1 (randomization). | Baseline, days 8,15,22 and 29 | 
| Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over 4 Weeks of Treatment | Rescue medication data recorded during the 14 day run-in period is used to calculate the baseline. - Total number of puffs of rescue medication per day over the full 4 weeks is calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the subject. - MIXED model: Change = treatment + gender + baseline mean daily number of puffs + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region. | Baseline and 4 weeks | 
| Percentage of Days With no Rescue Medication Use Over 4 Weeks of Treatment | Mixed model used: percentage of days with no rescue medication use = treatment + age + gender + baseline percentage of days with no rescue use + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region. A day with no rescue use is defined from diary data as any day where the subject does not use any puffs of rescue medication. The total number of days with no rescue use over the 4 week treatment period is divided by the total number of evaluable days in order to derive the percentage of days with no rescue use. | 4 weeks | 
| Fractional Exhaled Nitric Oxide (FeNO) | FeNO is widely accepted as a non-invasive marker for airway inflammation such as asthma and conducted according to published guideline. FeNO was measured on days 15 and 29 after treatment. | Days 15 and 29 | 
| Plasma Cortisol Concentrations | Blood samples were taken from each subject participating in the study post dose at day 1 and week 4. Cortisol concentrations were evaluated. Results are presented as nmol/L | Baseline, days 1 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma