Safety of QMF149 Twisthaler® in Adolescent and Adult Patients With Asthma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: QMF149 Twisthaler® Drug: Mometasone Twisthaler®	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Mometasone furoate Mometasone furoate monohydrate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Time to First Serious Asthma Exacerbation [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Cumulative Incidence of the First Serious Asthma Exacerbation Resulting in Hospitalization, Intubation or Death. [ Time Frame: up to 21 months ] [ Designated as safety issue: No ]
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.
Patients With Asthma Exacerbations That Required Treatment With Systemic Corticosteroids [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
Number of patients requiring treatment with systemic corticosteroids (oral or parenteral) over the course of the study (up to 21 months).
Number of Patients With at Least One Asthma Worsening Post-baseline [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
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).
Change From Baseline in Trough Forced Expiration Volume in 1 Second (FEV1) at Final Visit [ Time Frame: Baseline to the end of treatment (varying durations, up to 21 months) ] [ Designated as safety issue: No ]
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.
Change From Baseline in Forced Expiration Volume in 1 Second (FEV1) at Final Visit [ 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 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Forced Vital Capacity (FVC) at Final Visit [ 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 ] [ Designated as safety issue: No ]
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.
Changes From Baseline in Morning Peak Expiratory Flow (PEF) and Trough Evening PEF Averaged Over the Entire Post-baseline Period [ Time Frame: Baseline to the end of treatment (varying durations, up to 21 months) ] [ Designated as safety issue: No ]
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.
Change From Baseline in Percentage of Days With no Asthma Symptoms During the Morning, Daytime and Nighttime [ Time Frame: Baseline to the end of treatment (varying durations, up to 21 months) ] [ Designated as safety issue: No ]
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.
Change From Baseline in Average Asthma Symptom Score Total, Daytime and Nighttime [ Time Frame: Baseline to the end of treatment (varying durations, up to 21 months) ] [ Designated as safety issue: No ]
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.
Change From Baseline in Percentage of Days With no Rescue Medication Use During 24 Hours, Daytime and Nighttime [ Time Frame: Baseline to the end of treatment (varying durations, up to 21 months) ] [ Designated as safety issue: No ]
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.
Change From Baseline in Asthma Control Questionnaire (ACQ) at Final Visit [ Time Frame: Baseline to the end of treatment (varying durations, up to 21 months) ] [ Designated as safety issue: No ]
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.

Enrollment:	2283
Study Start Date:	July 2009
Study Completion Date:	May 2011
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: QMF149 Twisthaler® 500/400 QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Drug: QMF149 Twisthaler® Once daily via multi-dose dry-powder inhaler
Active Comparator: Mometasone Twisthaler® Mometasone Twisthaler®, 400 µg QD	Drug: Mometasone Twisthaler® Once daily via multi-dose dry-powder inhaler

Eligibility

Ages Eligible for Study:	12 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941798

Show 146 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00941798 History of Changes
Other Study ID Numbers:	CQMF149A2210, EudraCT number 2009-011539-10
Study First Received:	July 14, 2009
Results First Received:	May 3, 2012
Last Updated:	August 21, 2012
Health Authority:	United States: Food and Drug Administration India: Drugs Controller General of India Slovakia: State Institute for Drug Control Czech Republic: State Institute for Drug Control Hungary: National Institute of Pharmacy Korea: Food and Drug Administration

Keywords provided by Novartis:

Asthma
LABA
Safety

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate

Hypersensitivity
Immune System Diseases
Mometasone furoate
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 16, 2013