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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00941798
• Other study ID #: CQMF149A2210
• Secondary ID: EudraCT number 2
• Status: Completed
• Phase: Phase 2
• First received: July 14, 2009
• Last updated: August 21, 2012
• Start date: July 2009
• Est. completion date: May 2011

Study information

• Verified date: August 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIndia: Drugs Controller General of IndiaSlovakia: State Institute for Drug ControlCzech Republic: State Institute for Drug ControlHungary: National Institute of PharmacyKorea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2283
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• QMF149 Twisthaler®
Once daily via multi-dose dry-powder inhaler
• Mometasone Twisthaler®
Once daily via multi-dose dry-powder inhaler

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	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
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Czech Republic	Novartis Investigator Site	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 Investigative Site	Trutnov
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigator Site	Deszk
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Mosonmagyarovar
Hungary	Novartis Investigative Site	Nyiregyhaza
Hungary	Novartis Investigative Site	Tatabanya
Hungary	Novartis Investigative Site	Torokbalint
India	Novartis Investigator Site	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
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative SIte	Seoul
Korea, Republic of	Novartis Investigator Site	Seoul
Peru	Novartis Investigator Site	Lima
Slovakia	Novartis Investigator Site	Bardejov
Slovakia	Novartis Investigative Site	Bojnice
Slovakia	Novartis Investigator 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 Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Surany
Slovakia	Novartis Investigator Site	Trencin
Slovakia	Novartis Investigator Site	Vrable
United States	Novartis Investigative Site	Abingdon	Virginia
United States	Novartis Investigative Site	Albany	Georgia
United States	Novartis Investigator Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bangor	Maine
United States	Novartis Investigator Site	Bellevue	Nebraska
United States	Novartis Investigator Site	Birmingham	Alabama
United States	Novartis Investigative Site	Blue Bell	Pennsylvania
United States	Novartis Investigative Site	Brick	New Jersey
United States	Novartis Investigator Site	Buena Park	California
United States	Novartis Investigator Site	Canton	Ohio
United States	Novartis Investigative Site	Cedar Knolls	New Jersey
United States	Novartis Investigator Site	Chicago	Illinois
United States	Novartis Investigator Site	Clearwater	Florida
United States	Novartis Investigator Site	Clearwater	Florida
United States	Novartis Investigative Site	Columbus	Georgia
United States	Novartis Investigator Site	Columbus	Ohio
United States	Novartis Investigator Site	Couer D'Alene	Idaho
United States	Novartis Investigator Site	Dallas	Texas
United States	Novartis Investigator Site	Dallas	Texas
United States	Novartis Investigator Site	Denver	Colorado
United States	Novartis Investigator Site	Dickinson	Texas
United States	Novartis Investigator Site	El Paso	Texas
United States	Novartis Investigator Site	Encinitas	California
United States	Novartis Investigator Site	Engelwood	Colorado
United States	Novartis Investigator Site	Evansville	Indiana
United States	Novartis Investigator Site	Fort Worth	Texas
United States	Novartis Investigator Site	Fullerton	California
United States	Novartis Investigative Site	High Point	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigator Site	Houston	Texas
United States	Novartis Investigator Site	Indianapolis	Indiana
United States	Novartis Investigator Site	Iowa City	Iowa
United States	Novartis Investigator Site	Kingsport	Tennessee
United States	Novartis Investigator Site	Kirkland	Washington
United States	Novartis Investigator Site	Lakewood	Colorado
United States	Novartis Investigator Site	Lincoln	Rhode Island
United States	Novartis Investigator Site	Long Beach	California
United States	Novartis Investigator Site	Los Angeles	California
United States	Novartis Investigator Site	Marion	Ohio
United States	Novartis Investigator Site	Metarie	Louisiana
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigator Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Mineola	New York
United States	Novartis Investigator Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Mt. Pleasant	South Carolina
United States	Novartis Investigator Site	New Braunfels	Texas
United States	Novartis Investigative Site	Newburgh	New York
United States	Novartis Investigator Site	Normal	Illinois
United States	Novartis Investigative Site	North Dartmouth	Massachusetts
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigator Site	Oklahoma City	Oklahoma
United States	Novartis Investigator Site	Oklahoma City	Oklahoma
United States	Novartis Investigator Site	Omaha	Nebraska
United States	Novartis Investigator Site	Omaha	Nebraska
United States	Novartis Investigator Site	Orange	California
United States	Novartis Investigator Site	Owensboro	Kentucky
United States	Novartis Investigator Site	Ozark	Missouri
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigator Site	Plymouth	Minnesota
United States	Novartis Investigator Site	Port Charlotte	Florida
United States	Novartis Investigator Site	Portland	Oregon
United States	Novartis Investigative site	Raleigh	North Carolina
United States	Novartis Investigator Site	River Forest	Illinois
United States	Novartis Investigator Site	Riverside	California
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigator Site	Rolla	Missouri
United States	Novartis Investigator Site	San Antonio	Texas
United States	Novartis Investigator Site	San Diego	California
United States	Novartis Investigator Site	San Jose	California
United States	Novartis Investigator Site	San Mateo	California
United States	Novartis Investigator Site	Sarasota	Florida
United States	Novartis Investigative Site	Savannah	Georgia
United States	Novartis Investigator Site	Seattle	Washington
United States	Novartis Investigative Site	Skillman	New Jersey
United States	Novartis Investigator Site	Skokie	Illinois
United States	Novartis Investigative Site	South Burlington	Vermont
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigator Site	Springfield	Illinois
United States	Novartis Investigator Site	St. Louis	Missouri
United States	Novartis Investigator Site	Sylvania	Ohio
United States	Novartis Investigator Site	Tacoma	Washington
United States	Novartis Investigator Site	Tampa	Florida
United States	Novartis Investigator Site	Topeka	Kansas
United States	Novartis Investigator Site	Vista	California
United States	Novartis Investigator Site	Walnut Creek	California
United States	Novartis Investigator Site	Warrensburg	Missouri
United States	Novartis Investigator Site	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Colombia,  Czech Republic,  Hungary,  India,  Korea, Republic of,  Peru,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No