Safety of QMF149 Twisthaler® in Adolescent and Adult Patients With Asthma

Study Overview
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Brief Summary
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Study CQMF149A2210 evaluated the safety of QMF149 Twisthaler® 500/400 μg, a fixed dose combination of indacaterol 500 μg, a once daily β2 agonist, and mometasone furoate 400 μg, an inhaled corticosteroid (ICS) that is approved for use in the treatment of asthma. The objective of this safety trial was to assess the effect of treatment on the incidence of serious asthma exacerbations, defined as asthma related hospitalization and/or intubation and/or death. This was an event driven trial.

Official Title
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A Randomized, Multi-center, Parallel Group, Double Blind, Study to Assess the Safety of QMF Twisthaler® (500/400 µg) and Mometasone Furoate Twisthaler® (400 µg) in Adolescent and Adult Patients With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: QMF149 Twisthaler®
* Drug: Mometasone Twisthaler®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a documented diagnosis of persistent asthma and who were currently treated with or qualified for treatment with both ICS and long-acting beta2-agonist (LABA) combination Patients demonstrating an increase in forced expiration volume in 1 second (FEV1) of ≥ 12% or ≥ 200 mLs within 30 minutes after administration of short-acting beta2-agonist (SABA) Patients with an FEV1 ≥ 50% of predicted normal Exclusion Criteria: Patients with a previous diagnosis of chronic obstructive pulmonary disease (COPD) Patients who had an asthma attack/exacerbation requiring hospitalization/emergency room visit or respiratory tract infection within 1 month prior to randomization Patients who had ever required ventilator support for respiratory failure Patients with diabetes Type I or uncontrolled diabetes Type II Patients with concomitant pulmonary disease Patients with certain cardiovascular co-morbid conditions Patients with any significant medical condition that might compromise patient safety, interfere with evaluation or preclude completion of the study Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QMF149 Twisthaler® 500/400<br>QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD) | Drug: QMF149 Twisthaler®<br>* Once daily via multi-dose dry-powder inhaler<br>|
| Active Comparator: Mometasone Twisthaler®<br>Mometasone Twisthaler®, 400 µg QD | Drug: Mometasone Twisthaler®<br>* Once daily via multi-dose dry-powder inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Serious Asthma Exacerbation | Defined as the number of days from start of treatment up to the first date when an asthma exacerbation becomes serious. A serious asthma exacerbation was one that resulted in hospitalization, intubation or death. | Up to 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of the First Serious Asthma Exacerbation Resulting in Hospitalization, Intubation or Death. | The number of patients with at least one serious asthma exacerbation over the course of the study. A serious asthma exacerbation was one that resulted in hospitalization, intubation or death. | up to 21 months | 
| Patients With Asthma Exacerbations That Required Treatment With Systemic Corticosteroids | Number of patients requiring treatment with systemic corticosteroids (oral or parenteral) over the course of the study (up to 21 months). | Up to 21 months | 
| Number of Patients With at Least One Asthma Worsening Post-baseline | The criterion for asthma worsening were: decrease in peak expiratory flow (PEF) >= 20% from mean baseline on >= 3 consecutive days, nighttime symptom score >= 2 on >= 2 consecutive nights, decrease in forced expiration volume in 1 second (FEV1) >=20% from baseline at evening visits, daytime symptom score of 3 or 4 on >= 2 consecutive days, requiring an urgent unscheduled visit for medical care, 24 hour rescue medication use >= 8 puffs on >= 2 consecutive days, and any other clinically important symptoms (pre-specified MedDRA preferred terms). | Up to 21 months | 
| Change From Baseline in Trough Forced Expiration Volume in 1 Second (FEV1) at Final Visit | Spirometry was conducted according to internationally accepted standards. Trough FEV1 was measured 15 minutes before dosing; measurements within 6 hours of rescue medication use were set to missing. Repeated measures of analysis of covariance model: change from baseline to trough FEV1 = treatment + visit + treatment*visit interaction + baseline FEV1 + region + asthma related hospitalization in the last 12 months + asthma worsening in the last 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months) | 
| Change From Baseline in Forced Expiration Volume in 1 Second (FEV1) at Final Visit | Spirometry was conducted according to internationally accepted standards. Change from baseline at final visit. FEV1 data taken within 6 hours of rescue medication was excluded from the analysis. Repeated measures of analysis of covariance model: change from baseline to final visit FEV1 = treatment + visit + treatment*visit interaction + baseline FEV1 + region + asthma related hospitalization in the last 12 months + asthma worsening in the last 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months). At the following timepoints: 5 minutes post-dose, 30 minutes post-dose, 1 hour post-dose and 2 hours post-dose | 
| Change From Baseline in Forced Vital Capacity (FVC) at Final Visit | Spirometry was conducted according to internationally accepted standards. Change from baseline at final visit. FVC data taken within 6 hours of rescue medication was excluded from the analysis. Repeated measures of analysis of covariance model: change from baseline to final visit FVC = treatment + visit + treatment*visit interaction + baseline FVC + region + asthma related hospitalization in the last 12 months + asthma worsening in the last 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months). At the following timepoints: 5 minutes post-dose, 30 minutes post-dose, 1 hour post-dose and 2 hours post-dose | 
| Changes From Baseline in Morning Peak Expiratory Flow (PEF) and Trough Evening PEF Averaged Over the Entire Post-baseline Period | PEF was performed every morning and evening prior to study medication use except evenings on the day of clinic visits. Baseline is average over the last 14 days prior to start of treatment. Analysis of covariance model: change from baseline in PEF = treatment + baseline PEF + region + history of asthma related hospitalization in the past 12 months + history of asthma worsening in the past 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months) | 
| Change From Baseline in Percentage of Days With no Asthma Symptoms During the Morning, Daytime and Nighttime | Baseline = the last 14 days prior to start of treatment. Analysis of covariance model: Change from baseline = treatment + baseline value + region + history of asthma related hospitalization in past 12 months + history of asthma worsening in past 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months) | 
| Change From Baseline in Average Asthma Symptom Score Total, Daytime and Nighttime | Total asthma symptom score = morning symptoms (0, 1) + daytime score (0-4) + nighttime score (0-4). The range is from 0 to 9. A lower number indicates improvement. Baseline = the last 14 days prior to start of treatment. Analysis of covariance model: Change from baseline = treatment + baseline value + region + history of asthma related hospitalization in past 12 months + history of asthma worsening in past 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months) | 
| Change From Baseline in Percentage of Days With no Rescue Medication Use During 24 Hours, Daytime and Nighttime | 24 hours consists of both 12 hour daytime and 12 hour nighttime. Baseline = the last 14 days prior to start of treatment. Analysis of covariance model: Change from baseline = treatment + baseline value + region + history of asthma related hospitalization in past 12 months + history of asthma worsening in past 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months) | 
| Change From Baseline in Asthma Control Questionnaire (ACQ) at Final Visit | The Asthma Control Questionnaire score ranges from 0 (good control of asthma) to 6 (poor control of asthma). A negative change in score indicates improvement in asthma control. Repeated measures of analysis of covariance model: change from baseline in ACQ score = treatment + visit + treatment*visit interaction + baseline ACQ score + region + asthma related hospitalization in the last 12 months + asthma worsening in the last 12 months + African American patient. | Baseline to the end of treatment (varying durations, up to 21 months) | 

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