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

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

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 Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: QMF149 Twisthaler®; Drug: Mometasone Twisthaler®

• Study Type: Interventional
• Enrollment (Actual): 2283
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • Novartis Investigative Site
  • Florianopolis, Brazil
    • Novartis Investigative Site
  • Porto Alegre, Brazil
    • Novartis Investigative Site
  • Rio de Janeiro, Brazil
    • Novartis Investigative Site
  • Salvador, Brazil
    • Novartis Investigative Site
  • Sao Paulo, Brazil
    • Novartis Investigative Site
• Colombia
  • Barranquilla, Colombia
    • Novartis Investigative Site
  • Bogota, Colombia
    • Novartis Investigative Site
• Czech Republic
  • Boskovice, Czech Republic
    • Novartis Investigator Site
  • Breclav, Czech Republic
    • Novartis Investigator Site
  • Brno, Czech Republic
    • Novartis Investigator Site
  • Brno - Bohunice, Czech Republic
    • Novartis Investigator Site
  • Hradec Kralove, Czech Republic
    • Novartis Investigator Site
  • Jablonec nad Nisou, Czech Republic
    • Novartis Investigator Site
  • Kladno, Czech Republic
    • Novartis Investigator Site
  • Kutna Hora, Czech Republic
    • Novartis Investigator Site
  • Liberec, Czech Republic
    • Novartis Investigator Site
  • Most, Czech Republic
    • Novartis Investigator Site
  • Plzen, Czech Republic
    • Novartis Investigator Site
  • Praha, Czech Republic
    • Novartis Investigator Site
  • Tabor, Czech Republic
    • Novartis Investigator Site
  • Teplice, Czech Republic
    • Novartis Investigator Site
  • Trutnov, Czech Republic
    • Novartis Investigative Site
• Hungary
  • Balassagyarmat, Hungary
    • Novartis Investigative Site
  • Debrecen, Hungary
    • Novartis Investigative Site
  • Deszk, Hungary
    • Novartis Investigator Site
  • Gyor, Hungary
    • Novartis Investigative Site
  • Mosonmagyarovar, Hungary
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary
    • Novartis Investigative Site
  • Tatabanya, Hungary
    • Novartis Investigative Site
  • Torokbalint, Hungary
    • Novartis Investigative Site
• India
  • Chennai, India
    • Novartis Investigator Site
  • Coimbatore, India
    • Novartis Investigator Site
  • Hyderabaad, India
    • Novartis Investigator Site
  • Indore, India
    • Novartis Investigator Site
  • Mangalore, India
    • Novartis Investigator Site
  • Mumbai, India
    • Novartis Investigator Site
  • Nagpur, India
    • Novartis Investigator Site
  • Panjim, India
    • Novartis Investigator Site
• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Novartis Investigative Site
  • Seoul, Korea, Republic of
    • Novartis Investigative Site
  • Seoul, Korea, Republic of
    • Novartis Investigator Site
• Peru
  • Lima, Peru
    • Novartis Investigator Site
• Slovakia
  • Bardejov, Slovakia
    • Novartis Investigator Site
  • Bojnice, Slovakia
    • Novartis Investigative Site
  • Bratislava, Slovakia
    • Novartis Investigator Site
  • Kosice, Slovakia
    • Novartis Investigator Site
  • Levice, Slovakia
    • Novartis Investigator Site
  • Liptovsky Hradok, Slovakia
    • Novartis Investigator Site
  • Michalovce, Slovakia
    • Novartis Investigator Site
  • Nitra, Slovakia
    • Novartis Investigative Site
  • Surany, Slovakia
    • Novartis Investigative Site
  • Trencin, Slovakia
    • Novartis Investigator Site
  • Vrable, Slovakia
    • Novartis Investigator Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Novartis Investigator Site
  • California
    • Buena Park, California, United States, 90620
      • Novartis Investigator Site
    • Encinitas, California, United States, 92024
      • Novartis Investigator Site
    • Fullerton, California, United States, 92835
      • Novartis Investigator Site
    • Long Beach, California, United States, 90808
      • Novartis Investigator Site
    • Los Angeles, California, United States, 90025
      • Novartis Investigator Site
    • Orange, California, United States, 92868
      • Novartis Investigator Site
    • Riverside, California, United States, 92506
      • Novartis Investigator Site
    • San Diego, California, United States, 92123
      • Novartis Investigator Site
    • San Jose, California, United States, 95117
      • Novartis Investigator Site
    • San Mateo, California, United States, 94401
      • Novartis Investigator Site
    • Vista, California, United States, 92083
      • Novartis Investigator Site
    • Walnut Creek, California, United States, 94598
      • Novartis Investigator Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Novartis Investigator Site
    • Engelwood, Colorado, United States, 80112
      • Novartis Investigator Site
    • Lakewood, Colorado, United States, 80401
      • Novartis Investigator Site
    • Wheat Ridge, Colorado, United States, 80033
      • Novartis Investigator Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Novartis Investigator Site
    • Clearwater, Florida, United States, 33756
      • Novartis Investigator Site
    • Miami, Florida, United States, 33136
      • Novartis Investigative Site
    • Miami, Florida, United States, 33157
      • Novartis Investigative Site
    • Port Charlotte, Florida, United States, 33952
      • Novartis Investigator Site
    • Sarasota, Florida, United States, 34233
      • Novartis Investigator Site
    • South Miami, Florida, United States, 33143
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33603
      • Novartis Investigator Site
  • Georgia
    • Albany, Georgia, United States, 31707
      • Novartis Investigative Site
    • Columbus, Georgia, United States, 31904
      • Novartis Investigative Site
    • Savannah, Georgia, United States, 31406
      • Novartis Investigative Site
  • Idaho
    • Couer D'Alene, Idaho, United States, 83814
      • Novartis Investigator Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Novartis Investigator Site
    • Normal, Illinois, United States, 61761
      • Novartis Investigator Site
    • River Forest, Illinois, United States, 60305
      • Novartis Investigator Site
    • Skokie, Illinois, United States, 60076
      • Novartis Investigator Site
    • Springfield, Illinois, United States, 62703
      • Novartis Investigator Site
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Novartis Investigator Site
    • Indianapolis, Indiana, United States, 46208
      • Novartis Investigator Site
  • Iowa
    • Iowa City, Iowa, United States, 52240
      • Novartis Investigator Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novartis Investigator Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Novartis Investigator Site
  • Louisiana
    • Metarie, Louisiana, United States, 70002
      • Novartis Investigator Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Novartis Investigative Site
    • Baltimore, Maryland, United States, 21236
      • Novartis Investigative Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigator Site
    • Plymouth, Minnesota, United States, 55441
      • Novartis Investigator Site
  • Missouri
    • Ozark, Missouri, United States, 65721
      • Novartis Investigator Site
    • Rolla, Missouri, United States, 65401
      • Novartis Investigator Site
    • St. Louis, Missouri, United States, 63141
      • Novartis Investigator Site
    • Warrensburg, Missouri, United States, 64093
      • Novartis Investigator Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Novartis Investigator Site
    • Omaha, Nebraska, United States, 68130
      • Novartis Investigator Site
    • Omaha, Nebraska, United States, 68131
      • Novartis Investigator Site
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Novartis Investigative Site
    • Cedar Knolls, New Jersey, United States, 07927
      • Novartis Investigative Site
    • Skillman, New Jersey, United States, 08558
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Novartis Investigator Site
  • New York
    • Mineola, New York, United States, 11501
      • Novartis Investigative Site
    • Newburgh, New York, United States, 12550
      • Novartis Investigative Site
    • Rochester, New York, United States, 14618-2638
      • Novartis Investigative Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Novartis Investigative Site
    • Raleigh, North Carolina, United States, 27607
      • Novartis Investigative Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Novartis Investigator Site
    • Columbus, Ohio, United States, 43213
      • Novartis Investigator Site
    • Marion, Ohio, United States, 43302
      • Novartis Investigator Site
    • Sylvania, Ohio, United States, 43560
      • Novartis Investigator Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novartis Investigative Site
    • Oklahoma City, Oklahoma, United States, 73120
      • Novartis Investigator Site
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigator Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Novartis Investigator Site
  • Pennsylvania
    • Blue Bell, Pennsylvania, United States, 19422
      • Novartis Investigative Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Novartis Investigative Site
    • Philadelphia, Pennsylvania, United States, 19115
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15221
      • Novartis Investigative Site
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Novartis Investigator Site
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Novartis Investigative Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Novartis Investigator Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Novartis Investigator Site
    • Dallas, Texas, United States, 75230
      • Novartis Investigator Site
    • Dickinson, Texas, United States, 77539
      • Novartis Investigator Site
    • El Paso, Texas, United States, 79925
      • Novartis Investigator Site
    • Fort Worth, Texas, United States, 76132
      • Novartis Investigator Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • Houston, Texas, United States, 77054
      • Novartis Investigator Site
    • New Braunfels, Texas, United States, 78130
      • Novartis Investigator Site
    • San Antonio, Texas, United States, 78229
      • Novartis Investigator Site
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Novartis Investigative Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Novartis Investigative Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Novartis Investigator Site
    • Seattle, Washington, United States, 98105
      • Novartis Investigator Site
    • Tacoma, Washington, United States, 98405
      • Novartis Investigator Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Beasley RW, Donohue JF, Mehta R, Nelson HS, Clay M, Moton A, Kim HJ, Hederer BM. Effect of once-daily indacaterol maleate/mometasone furoate on exacerbation risk in adolescent and adult asthma: a double-blind randomised controlled trial. BMJ Open. 2015 Feb 3;5(2):e006131. doi: 10.1136/bmjopen-2014-006131.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: July 14, 2009
• First Submitted That Met QC Criteria: July 17, 2009
• First Posted (ESTIMATE): July 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 31, 2012
• Last Update Submitted That Met QC Criteria: August 21, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Safety; Asthma; LABA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Inflammatory Agents; Dermatologic Agents; Anti-Allergic Agents; Mometasone Furoate
• Other Study ID Numbers: CQMF149A2210; EudraCT number 2009-011539-10