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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00941798
• Collaborator: (none)
• Enrollment: 2,283
• Locations: 146
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 15.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: QMF149 Twisthaler®; Drug: Mometasone Twisthaler®	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2283 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time to First Serious Asthma Exacerbation [Up to 21 months]

   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

1. Cumulative Incidence of the First Serious Asthma Exacerbation Resulting in Hospitalization, Intubation or Death. [up to 21 months]

   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.

2. Patients With Asthma Exacerbations That Required Treatment With Systemic Corticosteroids [Up to 21 months]

   Number of patients requiring treatment with systemic corticosteroids (oral or parenteral) over the course of the study (up to 21 months).

3. Number of Patients With at Least One Asthma Worsening Post-baseline [Up to 21 months]

   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).

4. Change From Baseline in Trough Forced Expiration Volume in 1 Second (FEV1) at Final Visit [Baseline to the end of treatment (varying durations, up to 21 months)]

   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.

5. Change From Baseline in Forced Expiration Volume in 1 Second (FEV1) at Final Visit [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]

   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.

6. Change From Baseline in Forced Vital Capacity (FVC) at Final Visit [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]

   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.

7. Changes From Baseline in Morning Peak Expiratory Flow (PEF) and Trough Evening PEF Averaged Over the Entire Post-baseline Period [Baseline to the end of treatment (varying durations, up to 21 months)]

   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.

8. Change From Baseline in Percentage of Days With no Asthma Symptoms During the Morning, Daytime and Nighttime [Baseline to the end of treatment (varying durations, up to 21 months)]

   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.

9. Change From Baseline in Average Asthma Symptom Score Total, Daytime and Nighttime [Baseline to the end of treatment (varying durations, up to 21 months)]

   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.

10. Change From Baseline in Percentage of Days With no Rescue Medication Use During 24 Hours, Daytime and Nighttime [Baseline to the end of treatment (varying durations, up to 21 months)]

    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.

11. Change From Baseline in Asthma Control Questionnaire (ACQ) at Final Visit [Baseline to the end of treatment (varying durations, up to 21 months)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Birmingham	Alabama	United States	35209
2	Novartis Investigator Site	Buena Park	California	United States	90620
3	Novartis Investigator Site	Encinitas	California	United States	92024
4	Novartis Investigator Site	Fullerton	California	United States	92835
5	Novartis Investigator Site	Long Beach	California	United States	90808
6	Novartis Investigator Site	Los Angeles	California	United States	90025
7	Novartis Investigator Site	Orange	California	United States	92868
8	Novartis Investigator Site	Riverside	California	United States	92506
9	Novartis Investigator Site	San Diego	California	United States	92123
10	Novartis Investigator Site	San Jose	California	United States	95117
11	Novartis Investigator Site	San Mateo	California	United States	94401
12	Novartis Investigator Site	Vista	California	United States	92083
13	Novartis Investigator Site	Walnut Creek	California	United States	94598
14	Novartis Investigator Site	Denver	Colorado	United States	80230
15	Novartis Investigator Site	Engelwood	Colorado	United States	80112
16	Novartis Investigator Site	Lakewood	Colorado	United States	80401
17	Novartis Investigator Site	Wheat Ridge	Colorado	United States	80033
18	Novartis Investigator Site	Clearwater	Florida	United States	33756
19	Novartis Investigator Site	Clearwater	Florida	United States	33765
20	Novartis Investigative Site	Miami	Florida	United States	33136
21	Novartis Investigative Site	Miami	Florida	United States	33157
22	Novartis Investigator Site	Port Charlotte	Florida	United States	33952
23	Novartis Investigator Site	Sarasota	Florida	United States	34233
24	Novartis Investigative Site	South Miami	Florida	United States	33143
25	Novartis Investigator Site	Tampa	Florida	United States	33603
26	Novartis Investigative Site	Albany	Georgia	United States	31707
27	Novartis Investigative Site	Columbus	Georgia	United States	31904
28	Novartis Investigative Site	Savannah	Georgia	United States	31406
29	Novartis Investigator Site	Couer D'Alene	Idaho	United States	83814
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46	Novartis Investigator Site	Plymouth	Minnesota	United States	55441
47	Novartis Investigator Site	Ozark	Missouri	United States	65721
48	Novartis Investigator Site	Rolla	Missouri	United States	65401
49	Novartis Investigator Site	St. Louis	Missouri	United States	63141
50	Novartis Investigator Site	Warrensburg	Missouri	United States	64093
51	Novartis Investigator Site	Bellevue	Nebraska	United States	68123
52	Novartis Investigator Site	Omaha	Nebraska	United States	68130
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82	Novartis Investigator Site	Fort Worth	Texas	United States	76132
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87	Novartis Investigative Site	South Burlington	Vermont	United States	05403
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92	Novartis Investigator Site	Milwaukee	Wisconsin	United States	53209
93	Novartis Investigative Site	Belo Horizonte		Brazil
94	Novartis Investigative Site	Florianopolis		Brazil
95	Novartis Investigative Site	Porto Alegre		Brazil
96	Novartis Investigative Site	Rio de Janeiro		Brazil
97	Novartis Investigative Site	Salvador		Brazil
98	Novartis Investigative Site	Sao Paulo		Brazil
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100	Novartis Investigative Site	Bogota		Colombia
101	Novartis Investigator Site	Boskovice		Czech Republic
102	Novartis Investigator Site	Breclav		Czech Republic
103	Novartis Investigator Site	Brno - Bohunice		Czech Republic
104	Novartis Investigator Site	Brno		Czech Republic
105	Novartis Investigator Site	Hradec Kralove		Czech Republic
106	Novartis Investigator Site	Jablonec nad Nisou		Czech Republic
107	Novartis Investigator Site	Kladno		Czech Republic
108	Novartis Investigator Site	Kutna Hora		Czech Republic
109	Novartis Investigator Site	Liberec		Czech Republic
110	Novartis Investigator Site	Most		Czech Republic
111	Novartis Investigator Site	Plzen		Czech Republic
112	Novartis Investigator Site	Praha		Czech Republic
113	Novartis Investigator Site	Tabor		Czech Republic
114	Novartis Investigator Site	Teplice		Czech Republic
115	Novartis Investigative Site	Trutnov		Czech Republic
116	Novartis Investigative Site	Balassagyarmat		Hungary
117	Novartis Investigative Site	Debrecen		Hungary
118	Novartis Investigator Site	Deszk		Hungary
119	Novartis Investigative Site	Gyor		Hungary
120	Novartis Investigative Site	Mosonmagyarovar		Hungary
121	Novartis Investigative Site	Nyiregyhaza		Hungary
122	Novartis Investigative Site	Tatabanya		Hungary
123	Novartis Investigative Site	Torokbalint		Hungary
124	Novartis Investigator Site	Chennai		India
125	Novartis Investigator Site	Coimbatore		India
126	Novartis Investigator Site	Hyderabaad		India
127	Novartis Investigator Site	Indore		India
128	Novartis Investigator Site	Mangalore		India
129	Novartis Investigator Site	Mumbai		India
130	Novartis Investigator Site	Nagpur		India
131	Novartis Investigator Site	Panjim		India
132	Novartis Investigative Site	Gwangju		Korea, Republic of
133	Novartis Investigative SIte	Seoul		Korea, Republic of
134	Novartis Investigator Site	Seoul		Korea, Republic of
135	Novartis Investigator Site	Lima		Peru
136	Novartis Investigator Site	Bardejov		Slovakia
137	Novartis Investigative Site	Bojnice		Slovakia
138	Novartis Investigator Site	Bratislava		Slovakia
139	Novartis Investigator Site	Kosice		Slovakia
140	Novartis Investigator Site	Levice		Slovakia
141	Novartis Investigator Site	Liptovsky Hradok		Slovakia
142	Novartis Investigator Site	Michalovce		Slovakia
143	Novartis Investigative Site	Nitra		Slovakia
144	Novartis Investigative Site	Surany		Slovakia
145	Novartis Investigator Site	Trencin		Slovakia
146	Novartis Investigator Site	Vrable		Slovakia

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00941798
• Other Study ID Numbers: CQMF149A2210; EudraCT number 2009-011539-10
• First Posted: Jul 20, 2009
• Last Update Posted: Aug 31, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Novartis Pharmaceuticals: Asthma; LABA; Safety
• Additional relevant MeSH terms: Asthma; Mometasone Furoate

Study Results

Participant Flow

Pre-assignment Detail	2283 patients were screened. 1518 patients were randomized.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Period Title: Overall Study
STARTED	755	763
Full Analysis Set	749	759
COMPLETED	561	578
NOT COMPLETED	194	185

Baseline Characteristics

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®	Total
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD	Total of all reporting groups
Overall Participants	749	759	1508
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.4 (14.75)	42.3 (14.58)	42.3 (14.66)
Sex: Female, Male (Count of Participants)
Female	436 58.2%	449 59.2%	885 58.7%
Male	313 41.8%	310 40.8%	623 41.3%

Outcome Measures

1. Primary Outcome

Title	Time to First Serious Asthma Exacerbation
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	749	759
Median (Full Range) [months]	13.3	13.4

2. Secondary Outcome

Title	Cumulative Incidence of the First Serious Asthma Exacerbation Resulting in Hospitalization, Intubation or Death.
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	749	759
Number [participants]	2 0.3%	6 0.8%

3. Secondary Outcome

Title	Patients With Asthma Exacerbations That Required Treatment With Systemic Corticosteroids
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	749	759
Number [participants]	124 16.6%	171 22.5%

4. Secondary Outcome

Title	Number of Patients With at Least One Asthma Worsening Post-baseline
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	749	759
Number [participants]	533 71.2%	637 83.9%

5. Secondary Outcome

Title	Change From Baseline in Trough Forced Expiration Volume in 1 Second (FEV1) at Final Visit
Description	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.
Time Frame	Baseline to the end of treatment (varying durations, up to 21 months)

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	674	699
Least Squares Mean (Standard Error) [liters]	0.06 (0.025)	-0.07 (0.024)

6. Secondary Outcome

Title	Change From Baseline in Forced Expiration Volume in 1 Second (FEV1) at Final Visit
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	578	607
5 minutes post-dose (n = 578, 607)	0.09 (0.018)	-0.04 (0.018)
30 minutes post-dose (n = 576, 605)	0.12 (0.020)	-0.05 (0.020)
1 hour post-dose (n = 575, 602)	0.13 (0.021)	-0.06 (0.021)
2 hours post-dose (n = 568, 601)	0.14 (0.022)	-0.05 (0.022)

7. Secondary Outcome

Title	Change From Baseline in Forced Vital Capacity (FVC) at Final Visit
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	578	607
5 minutes post-dose (n = 578, 607)	-0.03 (0.023)	-0.11 (0.023)
30 minutes post-dose (n = 576, 605)	-0.03 (0.025)	-0.13 (0.024)
1 hour post-dose (n = 575, 602)	-0.01 (0.025)	-0.13 (0.025)
2 hours post-dose (n = 568, 601)	-0.02 (0.026)	-0.13 (0.026)

8. Secondary Outcome

Title	Changes From Baseline in Morning Peak Expiratory Flow (PEF) and Trough Evening PEF Averaged Over the Entire Post-baseline Period
Description	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)

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and at final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	731	748
Morning PEF (n = 730, 746)	0.43 (0.075)	0.00 (0.075)
Evening PEF (n = 731, 748)	0.27 (0.076)	-0.15 (0.075)

9. Secondary Outcome

Title	Change From Baseline in Percentage of Days With no Asthma Symptoms During the Morning, Daytime and Nighttime
Description	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)

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	731	749
Morning (n = 730, 746)	22.3 (2.17)	18.4 (2.17)
Daytime (n = 731, 749)	27.1 (2.96)	19.5 (2.95)
Nighttime (n = 730, 746)	23.6 (2.69)	17.3 (2.68)

10. Secondary Outcome

Title	Change From Baseline in Average Asthma Symptom Score Total, Daytime and Nighttime
Description	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)

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and endpoint were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	731	749
Total (n = 708, 733)	-1.22 (0.088)	-0.94 (0.088)
Daytime (n = 731, 749)	-0.50 (0.043)	-0.39 (0.043)
Nighttime (n = 730, 746)	-0.46 (0.037)	-0.36 (0.037)

11. Secondary Outcome

Title	Change From Baseline in Percentage of Days With no Rescue Medication Use During 24 Hours, Daytime and Nighttime
Description	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)

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	692	711
24 hours (n = 669, 696)	29.1 (2.88)	17.9 (2.88)
Daytime (n = 692, 711)	23.6 (2.74)	13.8 (2.74)
Nighttime (n = 691, 708)	24.6 (2.69)	14.5 (2.68)

12. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire (ACQ) at Final Visit
Description	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)

Outcome Measure Data

Analysis Population Description

Full analysis set: all randomized patients who received at least one dose of study medication. Participants with observations at both baseline and final visit were included in this analysis.

Arm/Group Title	QMF149 Twisthaler® 500/400	Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)	Mometasone Twisthaler®, 400 µg QD
Measure Participants	675	687
Least Squares Mean (Standard Error) [units on a scale]	-0.55 (0.052)	-0.32 (0.052)

Adverse Events

Arm/Group Title	QMF149 Twisthaler® 500/400		Mometasone Twisthaler®
Arm/Group Description	QMF149 Twisthaler® (indacaterol maleate 500 µg/mometasone furoate 400 µg), once daily (QD)		Mometasone Twisthaler®, 400 µg QD
All Cause Mortality
	QMF149 Twisthaler® 500/400		Mometasone Twisthaler®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	QMF149 Twisthaler® 500/400		Mometasone Twisthaler®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/749 (4%)		44/759 (5.8%)
Blood and lymphatic system disorders
Thrombocytopenia	1/749 (0.1%)		0/759 (0%)
Cardiac disorders
Angina pectoris	0/749 (0%)		1/759 (0.1%)
Angina unstable	1/749 (0.1%)		0/759 (0%)
Atrial fibrillation	0/749 (0%)		1/759 (0.1%)
Cardiac arrest	0/749 (0%)		1/759 (0.1%)
Coronary artery disease	1/749 (0.1%)		0/759 (0%)
Myocardial ischaemia	1/749 (0.1%)		0/759 (0%)
Palpitations	0/749 (0%)		1/759 (0.1%)
Stress cardiomyopathy	0/749 (0%)		1/759 (0.1%)
Supraventricular tachycardia	1/749 (0.1%)		1/759 (0.1%)
Eye disorders
Eye haemorrhage	1/749 (0.1%)		0/759 (0%)
Gastrointestinal disorders
Abdominal hernia obstructive	1/749 (0.1%)		0/759 (0%)
Abdominal pain	1/749 (0.1%)		0/759 (0%)
Haemorrhoids	0/749 (0%)		1/759 (0.1%)
Inguinal hernia	0/749 (0%)		2/759 (0.3%)
Nausea	2/749 (0.3%)		0/759 (0%)
Pancreatitis	1/749 (0.1%)		0/759 (0%)
Vomiting	2/749 (0.3%)		0/759 (0%)
General disorders
Chest pain	1/749 (0.1%)		2/759 (0.3%)
Cyst	0/749 (0%)		1/759 (0.1%)
Multi-organ failure	0/749 (0%)		1/759 (0.1%)
Non-cardiac chest pain	0/749 (0%)		2/759 (0.3%)
Pyrexia	1/749 (0.1%)		0/759 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/749 (0.1%)		0/759 (0%)
Cholelithiasis	2/749 (0.3%)		0/759 (0%)
Immune system disorders
Anaphylactic reaction	0/749 (0%)		1/759 (0.1%)
Infections and infestations
Abscess intestinal	0/749 (0%)		1/759 (0.1%)
Appendicitis	2/749 (0.3%)		2/759 (0.3%)
Cellulitis	1/749 (0.1%)		0/759 (0%)
Diverticulitis	0/749 (0%)		2/759 (0.3%)
External ear cellulitis	0/749 (0%)		1/759 (0.1%)
Gastroenteritis	1/749 (0.1%)		0/759 (0%)
Malaria	1/749 (0.1%)		0/759 (0%)
Pneumococcal sepsis	0/749 (0%)		1/759 (0.1%)
Pneumonia	0/749 (0%)		4/759 (0.5%)
Septic shock	0/749 (0%)		1/759 (0.1%)
Injury, poisoning and procedural complications
Concussion	1/749 (0.1%)		0/759 (0%)
Foot fracture	0/749 (0%)		1/759 (0.1%)
Lower limb fracture	0/749 (0%)		1/759 (0.1%)
Meniscus lesion	0/749 (0%)		1/759 (0.1%)
Pneumothorax traumatic	1/749 (0.1%)		0/759 (0%)
Rib fracture	1/749 (0.1%)		0/759 (0%)
Road traffic accident	1/749 (0.1%)		0/759 (0%)
Spinal compression fracture	1/749 (0.1%)		0/759 (0%)
Spinal fracture	1/749 (0.1%)		0/759 (0%)
Tendon rupture	0/749 (0%)		1/759 (0.1%)
Investigations
Electrocardiogram T wave inversion	0/749 (0%)		1/759 (0.1%)
Metabolism and nutrition disorders
Diabetes mellitus	0/749 (0%)		1/759 (0.1%)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder	0/749 (0%)		1/759 (0.1%)
Intervertebral disc protrusion	1/749 (0.1%)		0/759 (0%)
Osteoarthritis	0/749 (0%)		1/759 (0.1%)
Tendonitis	0/749 (0%)		1/759 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/749 (0%)		1/759 (0.1%)
Colon cancer	1/749 (0.1%)		0/759 (0%)
Malignant melanoma	1/749 (0.1%)		0/759 (0%)
Meningioma	0/749 (0%)		1/759 (0.1%)
Osteochondroma	0/749 (0%)		1/759 (0.1%)
Prostate cancer	1/749 (0.1%)		0/759 (0%)
Thyroid cancer	1/749 (0.1%)		1/759 (0.1%)
Nervous system disorders
Carotid artery occlusion	1/749 (0.1%)		0/759 (0%)
Cerebrovascular accident	0/749 (0%)		1/759 (0.1%)
Radicular pain	1/749 (0.1%)		0/759 (0%)
Transient ischaemic attack	0/749 (0%)		1/759 (0.1%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/749 (0%)		1/759 (0.1%)
Pregnancy	3/749 (0.4%)		1/759 (0.1%)
Psychiatric disorders
Abnormal behaviour	1/749 (0.1%)		0/759 (0%)
Reproductive system and breast disorders
Colpocele	0/749 (0%)		1/759 (0.1%)
Endometriosis	1/749 (0.1%)		0/759 (0%)
Ovarian mass	1/749 (0.1%)		0/759 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/749 (0.3%)		9/759 (1.2%)
Cough	0/749 (0%)		1/759 (0.1%)
Dyspnoea	0/749 (0%)		2/759 (0.3%)
Sinus polyp	1/749 (0.1%)		0/759 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/749 (0.1%)		0/759 (0%)
Surgical and medical procedures
Inguinal hernia repair	1/749 (0.1%)		0/759 (0%)
Vascular disorders
Aortic aneurysm	1/749 (0.1%)		0/759 (0%)
Other (Not Including Serious) Adverse Events
	QMF149 Twisthaler® 500/400		Mometasone Twisthaler®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	510/749 (68.1%)		477/759 (62.8%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	12/749 (1.6%)		8/759 (1.1%)
General disorders
Pyrexia	9/749 (1.2%)		14/759 (1.8%)
Infections and infestations
Acute sinusitis	16/749 (2.1%)		8/759 (1.1%)
Bronchitis	39/749 (5.2%)		58/759 (7.6%)
Influenza	26/749 (3.5%)		27/759 (3.6%)
Laryngitis	5/749 (0.7%)		12/759 (1.6%)
Lower respiratory tract infection	13/749 (1.7%)		9/759 (1.2%)
Nasopharyngitis	112/749 (15%)		106/759 (14%)
Pharyngitis	29/749 (3.9%)		27/759 (3.6%)
Respiratory tract infection	13/749 (1.7%)		15/759 (2%)
Rhinitis	21/749 (2.8%)		14/759 (1.8%)
Sinusitis	55/749 (7.3%)		52/759 (6.9%)
Upper respiratory tract infection	83/749 (11.1%)		96/759 (12.6%)
Upper respiratory tract infection bacterial	15/749 (2%)		21/759 (2.8%)
Urinary tract infection	14/749 (1.9%)		14/759 (1.8%)
Viral infection	10/749 (1.3%)		24/759 (3.2%)
Viral upper respiratory tract infection	29/749 (3.9%)		36/759 (4.7%)
Musculoskeletal and connective tissue disorders
Back pain	16/749 (2.1%)		11/759 (1.4%)
Nervous system disorders
Headache	26/749 (3.5%)		30/759 (4%)
Respiratory, thoracic and mediastinal disorders
Asthma	195/749 (26%)		269/759 (35.4%)
Cough	266/749 (35.5%)		63/759 (8.3%)
Nasal congestion	12/749 (1.6%)		13/759 (1.7%)
Oropharyngeal pain	24/749 (3.2%)		18/759 (2.4%)
Rhinitis allergic	29/749 (3.9%)		25/759 (3.3%)
Vascular disorders
Hypertension	13/749 (1.7%)		14/759 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.