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

Novartis Pharmaceuticals2,283 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,283

Conditions

Asthma

Interventions

QMF149 Twisthaler®DRUG

Once daily via multi-dose dry-powder inhaler

Mometasone Twisthaler®DRUG

Once daily via multi-dose dry-powder inhaler

Eligibility

Sex: ALLMin age: 12 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (146)

Outcomes

Primary Outcomes

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.

Time frame: Up to 21 months

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: 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.

Data from ClinicalTrials.gov

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Novartis Investigator Site

Birmingham, Alabama, United States

Novartis Investigator Site

Buena Park, California, United States

Novartis Investigator Site

Encinitas, California, United States

Novartis Investigator Site

Fullerton, California, United States

Novartis Investigator Site

Long Beach, California, United States

Novartis Investigator Site

Los Angeles, California, United States

Novartis Investigator Site

Orange, California, United States

Novartis Investigator Site

Riverside, California, United States

Novartis Investigator Site

San Diego, California, United States

Novartis Investigator Site

San Jose, California, United States

...and 136 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline to the end of treatment (varying durations, up to 21 months)