A Multicenter Randomized 52 Week Treatment Double-blind, Triple Dummy Parallel Group Study to Assess the Efficacy and Safety of QMF149 Compared to Mometasone Furoate in Participants With Asthma
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02554786
Collaborator
(none)
2,216
390
5
42
5.7
0.1
Study Details
Study Description
Brief Summary
The purpose of the trial is to evaluate the efficacy and safety of two different doses of QMF149 (QMF149 150/160 µg and QMF149 150/320 µg via Concept1) over two respective MF doses (MF 400 µg and MF 800 µg via Twisthaler® (total daily dose)) in poorly controlled asthmatic participants as determined by pulmonary function testing, and effects on asthma control
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
2216 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter Randomized 52 Week Treatment Double-blind, Triple Dummy Parallel Group Study to Assess the Efficacy and Safety of QMF149 Compared to Mometasone Furoate in Patients With Asthma
Actual Study Start Date
:
Dec 29, 2015
Actual Primary Completion Date
:
Nov 21, 2018
Actual Study Completion Date
:
Jun 28, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QMF149 150/160 µg QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered once daily (o.d) via Concept1 inhaler in the evening. |
Drug: Indacaterol acetate/Mometasone furoate
Other Names:
|
| Experimental: QMF149 150/320 µg QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d via Concept1 inhaler in the evening. |
Drug: Indacaterol acetate/Mometasone furoate
Other Names:
|
| Active Comparator: MF 400 µg Mometasone furoate (MF) 400 μg was delivered o.d via Twisthaler® in the evening |
Drug: Mometasone furoate
|
| Active Comparator: Salmeterol /fluticasone 50/500 μg Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
Drug: Salmeterol xinafoate/fluticasone propionate
|
| Active Comparator: MF 800 μg MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. |
Drug: Mometasone furoate
|
Outcome Measures
Primary Outcome Measures
- Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26 [26 weeks]
Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
Secondary Outcome Measures
- Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52 [Weeks 4, 12, 26 and 52]
The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway calibre (FEV1 % predicted). All 7 questions of the ACQ-7 were equally weighted. Items 1-5 were scored along a 7-point response scale, where 0 = totally controlled and 6 = severely uncontrolled. Item 6 is scored between 0 = no rescue medication and 6 = More than 16 puffs/inhalations most days. The 7th item was scored by the investigator based on the FEV1 % predicted from the masterscope at the site (i.e., Score = 0 means > 95% of predicted FEV1, 1 = 90 - 95%, 2 = 80 - 89%, 3 = 70 - 79%, 4 = 60 - 69%, 5 = 50 - 59%, and Score = 6 means < 50% of predicted FEV1). The total score was calculated as the mean of all questions.
- Trough FEV1 at Week 52 [Week 52]
Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
- Pre-dose FEV1 at Weeks 4 and 12 [Weeks 4 (Day 30) and 12 (Day 86)]
Pre-dose trough FEV1 is defined as average of the two FEV1 measurements taken 45 min and 15 min pre evening dose. It was assessed by performing spirometric assessment. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
- Post Dose FEV1 (5 Minutes-1 Hour) [Up to Week 52 (Day 364)]
Post-dose FEV1 measurements were analyzed at 5 minutes, 15 minutes, 30 minutes and 1 hour. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
- Trough Forced Vital Capacity (FVC) [Up to Week 52 (Day 365)]
FVC is the total amount of air exhaled during the FEV test. Trough FVC is defined as average of the two FVC measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. It was assessed by performing spirometric assessment.
- Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75) [Up to Week 52 (Day 365)]
FEF is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration. Trough FEF25-75% is defined as average of the two FEF25-75% measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. It was assessed by performing spirometric assessment.
- Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment [Up to Weeks 26 and 52]
PEF is a person's maximum speed of expiration. All the participants were instructed to record PEF twice daily using a mini Peak Flow Meter device, once in the morning (before taking the morning dose) and once approximately 12 h later in the evening (before taking the evening dose). At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the e-PEF/diary. The best of 3 values were used.
- Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52 [Weeks 26 (Day 183) and 52 (Day 364)]
Change from baseline in ACQ-7 scores of ≤ 0.5 was defined as minimal clinically important difference and were considered clinically meaningful. The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway calibre (FEV1 % predicted). All 7 questions of the ACQ-7 were equally weighted. Items 1-5 were scored along a 7-point response scale, where 0 = totally controlled and 6 = severely uncontrolled. Item 6 is scored between 0 = no rescue medication and 6 = More than 16 puffs/inhalations most days. The 7th item was scored by the investigator based on the FEV1 % predicted from the masterscope at the site (i.e., Score = 0 means > 95% of predicted FEV1, 1 = 90 - 95%, 2 = 80 - 89%, 3 = 70 - 79%, 4 = 60 - 69%, 5 = 50 - 59%, and Score = 6 means < 50% of predicted FEV1). The total score was calculated as the mean of all questions
- Change From Baseline in Percentage of Asthma Symptoms Free Days [Up to Week 52]
All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. Asthma symptoms free days are days with no daytime symptoms, no night-time awakenings and no symptoms on awakening. The daytime asthma symptom score was based on the daily e-diary recordings by participants with respect to shortness of breath, wheeze, cough, chest tightness, and impact on usual daily activities due to symptoms.
- Change Form Baseline in Percentage of Days With no Daytime Symptoms [Up to Week 52]
All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. For days with no daytime symptoms, all 5 evening questions must have a score = 0 with respect to shortness of breath, wheeze, cough, chest tightness and impact on usual daily activities due to symptoms, each with scores from 0 (no problems) to 4 (very severe problems).
- Change From Baseline in Percentage of Nights With no Night-time Awakenings [Up to Week 52]
All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. The question asked for nights with no night-time awakenings was "How did you sleep last night?" had to be answered with "I did not wake up because of any breathing problems" with scores from 0 (no problem)-4 (very severe problems).
- Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening [Up to Week 52]
All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. The question asked for mornings with no symptoms on awakening was "Did you have asthma symptoms upon awakening in the morning?" to be answered with "None" with scores from 0 (no problem)-4 (very severe problems).
- Rescue Medication Usage [Up to Weeks 26 and 52]
All participants were given salbutamol/albuterol to use as rescue medication throughout the study along with e-Diary to record rescue medication use. The number of puffs of rescue medication during the past 12 hours is recorded twice (morning/evening) by the participant prior to taking study medication. The mean daily number of puffs of rescue medication use will be calculated for each participant, done separately for morning (night-time), evening (daytime), and daily (night-time plus daytime) rescue medication use
- Time to First Asthma Exacerbation by Exacerbation Category [Up to Week 52]
The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.
- Time to First Hospitalization for Asthma Exacerbation [Up to Week 52]
The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.
- Annual Rate of Asthma Exacerbations by Exacerbation Category [Up to Week 52]
The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.
- Duration in Days of Asthma Exacerbations by Exacerbation Category [Up to Week 52]
The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.
- Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category [Up to Week 52]
The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.
- Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations [Up to Week 52]
The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.
- Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations [Up to Week 52]
- Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations [Up to Week 52]
The treatment of asthma exacerbations including the initiation of systemic corticosteroids were done according to investigator's or treating physician's medical judgement and in line with national and international recommendations. If systemic corticosteroids were required, a participant could return to the study after successfully completing a taper of approximately 7-10 days.
- Change From Baseline in Percentage of Rescue Medication Free Days [Up to Weeks 26 and 52]
All participants were given salbutamol/albuterol to use as rescue medication throughout the study along with e-Diary to record rescue medication use. Rescue medication free days is defined as any day where the participant did not use any puffs of rescue medication during daytime and night-time.
- Asthma Quality of Life Questionnaire (AQLQ) [Up to Week 52 (Day 364)]
AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). It consists of 4 domains: Symptoms = Mean of Items 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 29, 30 (12 items) Activity limitation = Mean of Items 1, 2, 3, 4, 5, 11, 19, 25, 28, 31, 32 (11 items) Emotional function = Mean of Items 7, 13, 15, 21, 27 (5 items) Environmental stimuli = Mean of Items 9, 17, 23, 26 (4 items) Overall Score = Mean of Items 1 to 32 (32 items)
- Trough FEV1 Measured After 26 Weeks of Treatment [Week 26]
Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
- Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes [Up to Week 52]
A composite endpoint of serious asthma outcomes is defined as asthma-related hospitalization, asthma-related intubation, or asthma-related death and was reviewed by the Adjudication Committee.
- Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Approximately up to 56 weeks]
An AE is any untoward medical occurrence (i.e., any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s) or medical conditions(s) which meets any one of the following criteria: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant, i.e. defined as an event that jeopardizes the participants or may require medical or surgical intervention.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participants with a diagnosis of asthma, for a period of at least 1 year prior to Visit 1 (Screening)
-
Participants who have used medium or high dose inhaled corticosteroids (ICS) or low dose of long acting beta-2 agonist (LABA)/ICS combinations for asthma for at least 3 months and at stable doses for at least 1 month prior to Visit 1
-
Participants must have ACQ-7 score ≥ 1.5 at Visit 101 and at Visit 102 (prior to double-blind treatment) and qualify for treatment with medium or high dose LABA/ICS
-
Pre-bronchodilator ≥ 50% Forced expiratory volume in 1 second (FEV1) of < 85 % of the predicted normal value for the participants after withholding bronchodilators at both Visit 101 and 102, according to American Thoracic Society/European Respiratory Society (ATS/ERS) criteria.
-
Withholding period of bronchodilators prior to spirometry: short acting beta-2 agonist (SABA) for ≥ 6 hours and FDC or free combinations of ICS/LABA for ≥ 48 hours, short acting anticholinergics (SAMA) for ≥ 8 hours, xanthines >=07 days
-
A one-time repeat/re-testing of percent predicted FEV1 (prebronchodilator FEV1) is allowed at Visit 101 and at Visit 102.
Spacer devices are permitted for reversibility testing only.
-Participants who demonstrate an increase in FEV1 of 12% and 200 mL within 30 minutes after administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose) at Visit 101 All participants must perform a reversibility test at Visit 101
If reversibility is not demonstrated at Visit 101:
-
Reversibility should be repeated once-
-
Participants may be permitted to enter the study with historical evidence of reversibility that was performed according to ATS/ERS guidelines within 2 years prior to Visit 1
-
Alternatively, participants may be permitted to enter the study with a historical positive bronchoprovocation test that was performed within 2 years prior to Visit 1.
Exclusion Criteria:
-
Participants who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years. This includes use of nicotine inhalers such as e-cigarettes at the time of Visit 1
-
Participants who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening)
-
Participants who have ever required intubation for a severe asthma attack/exacerbation.
-
Participants who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study).
-
Participants who have had a respiratory tract infection or asthma worsening as determined by the investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and Visit 102. Participants may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
-
Participants with a history of chronic lung diseases other than asthma, including (but not limited to) Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
-
Participants with severe narcolepsy and/or insomnia.
-
Participants who have a clinically significant electrocardiogram (ECG) abnormality at Visit 101 (Start of Run- In epoch) and at any time between Visit 101 and Visit 102 (including unscheduled ECG). ECG evidence of myocardial infarction at Visit 101 (via central reader) should be clinically assessed by the investigator with supportivedocumentation
-
Participants with a history of hypersensitivity to lactose, any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof
-
Participants who have not achieved an acceptable spirometry results at Visit 101 in accordance with ATS/ERS criteria for acceptability and repeatability (rescreening allowed only once).
Repeat spirometry may be allowed once in an ad-hoc visit if the spirometry did not qualify due to ATS/ERS criteria. If the participant fails the repeat assessment, the participant may be rescreened once
-
Participants on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or participants on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout the course of the study.
-
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and for 30 days after stopping of study treatment.
-
Long acting muscarinic antagonist (LAMA) use within 3 months prior to Visit 101
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Birmingham | Alabama | United States | 35244 |
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| 7 | Novartis Investigative Site | Stockton | California | United States | 95207 |
| 8 | Novartis Investigative Site | Westminster | California | United States | 92683 |
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| 77 | Novartis Investigative Site | Rijeka | Croatia | 51000 | |
| 78 | Novartis Investigative Site | Zadar | Croatia | 23000 | |
| 79 | Novartis Investigative Site | Zagreb | Croatia | 10000 | |
| 80 | Novartis Investigative Site | Beroun | Czech Republic | Czechia | 266 01 |
| 81 | Novartis Investigative Site | Boskovice | Czech Republic | Czechia | 680 01 |
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| 92 | Novartis Investigative Site | Cesky Krumlov | Czechia | 381 01 | |
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| 103 | Novartis Investigative Site | Koblenz | Rheinland-Pfalz | Germany | 56068 |
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| 110 | Novartis Investigative Site | Berlin | Germany | 10787 | |
| 111 | Novartis Investigative Site | Berlin | Germany | 10969 | |
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| 114 | Novartis Investigative Site | Berlin | Germany | 12203 | |
| 115 | Novartis Investigative Site | Berlin | Germany | 12627 | |
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| 119 | Novartis Investigative Site | Berlin | Germany | 13187 | |
| 120 | Novartis Investigative Site | Bochum | Germany | D-44787 | |
| 121 | Novartis Investigative Site | Boehlen | Germany | 04564 | |
| 122 | Novartis Investigative Site | Bonn | Germany | 53119 | |
| 123 | Novartis Investigative Site | Delitzsch | Germany | 04509 | |
| 124 | Novartis Investigative Site | Dresden | Germany | 01069 | |
| 125 | Novartis Investigative Site | Dueren | Germany | 52349 | |
| 126 | Novartis Investigative Site | Düsseldorf | Germany | 40211 | |
| 127 | Novartis Investigative Site | Erlangen | Germany | 91052 | |
| 128 | Novartis Investigative Site | Frankfurt | Germany | 60313 | |
| 129 | Novartis Investigative Site | Frankfurt | Germany | 60389 | |
| 130 | Novartis Investigative Site | Furstenwalde | Germany | 15517 | |
| 131 | Novartis Investigative Site | Halle | Germany | 06108 | |
| 132 | Novartis Investigative Site | Hamburg | Germany | 20354 | |
| 133 | Novartis Investigative Site | Hamburg | Germany | 22143 | |
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| 136 | Novartis Investigative Site | Hannover | Germany | 30173 | |
| 137 | Novartis Investigative Site | Hochstadt | Germany | 91315 | |
| 138 | Novartis Investigative Site | Kassel | Germany | 34121 | |
| 139 | Novartis Investigative Site | Leipzig | Germany | 04103 | |
| 140 | Novartis Investigative Site | Leipzig | Germany | 04109 | |
| 141 | Novartis Investigative Site | Leipzig | Germany | 04207 | |
| 142 | Novartis Investigative Site | Leipzig | Germany | 04275 | |
| 143 | Novartis Investigative Site | Lubeck | Germany | 23552 | |
| 144 | Novartis Investigative Site | Ludwigsburg | Germany | 71640 | |
| 145 | Novartis Investigative Site | Marburg | Germany | D-35037 | |
| 146 | Novartis Investigative Site | Mittweida | Germany | 09648 | |
| 147 | Novartis Investigative Site | Muenchen | Germany | 81377 | |
| 148 | Novartis Investigative Site | Neu Isenburg | Germany | 63263 | |
| 149 | Novartis Investigative Site | Neuss | Germany | 41462 | |
| 150 | Novartis Investigative Site | Potsdam | Germany | 14467 | |
| 151 | Novartis Investigative Site | Potsdam | Germany | 14469 | |
| 152 | Novartis Investigative Site | Rheine | Germany | 48431 | |
| 153 | Novartis Investigative Site | Rudersdorf | Germany | 15562 | |
| 154 | Novartis Investigative Site | Schleswig | Germany | 24837 | |
| 155 | Novartis Investigative Site | Schwedt | Germany | 16303 | |
| 156 | Novartis Investigative Site | Weinheim | Germany | 69469 | |
| 157 | Novartis Investigative Site | Witten | Germany | 58452 | |
| 158 | Novartis Investigative Site | Ciudad | Gautemala | Guatemala | 01010 |
| 159 | Novartis Investigative Site | Guatemala City | GTM | Guatemala | 01010 |
| 160 | Novartis Investigative Site | Guatemala City | GTM | Guatemala | 01011 |
| 161 | Novartis Investigative Site | Guatemala City | Guatemala | 01010 | |
| 162 | Novartis Investigative Site | Guatemala City | Guatemala | 01011 | |
| 163 | Novartis Investigative Site | Guatemala City | Guatemala | 01057 | |
| 164 | Novartis Investigative Site | Budapest | HUN | Hungary | 1037 |
| 165 | Novartis Investigative Site | Budapest | HUN | Hungary | 1089 |
| 166 | Novartis Investigative Site | Budapest | HUN | Hungary | 1117 |
| 167 | Novartis Investigative Site | Budapest | HUN | Hungary | 1204 |
| 168 | Novartis Investigative Site | Gyor | HUN | Hungary | 9024 |
| 169 | Novartis Investigative Site | Hajdunanas | HUN | Hungary | 4080 |
| 170 | Novartis Investigative Site | Mako | HUN | Hungary | 6900 |
| 171 | Novartis Investigative Site | Miskolc | HUN | Hungary | 3529 |
| 172 | Novartis Investigative Site | Puspokladany | HUN | Hungary | 4150 |
| 173 | Novartis Investigative Site | Szazhalombatta | HUN | Hungary | 2440 |
| 174 | Novartis Investigative Site | Balassagyarmat | Hungary | 2660 | |
| 175 | Novartis Investigative Site | Budapest | Hungary | 1106 | |
| 176 | Novartis Investigative Site | Budapest | Hungary | 1134 | |
| 177 | Novartis Investigative Site | Cegled | Hungary | 2700 | |
| 178 | Novartis Investigative Site | Csorna | Hungary | H-9300 | |
| 179 | Novartis Investigative Site | Dombovar | Hungary | 7200 | |
| 180 | Novartis Investigative Site | Godollo | Hungary | 2100 | |
| 181 | Novartis Investigative Site | Hatvan | Hungary | 3000 | |
| 182 | Novartis Investigative Site | Komarom | Hungary | 2900 | |
| 183 | Novartis Investigative Site | Miskolc | Hungary | 3526 | |
| 184 | Novartis Investigative Site | Mosdos | Hungary | 7257 | |
| 185 | Novartis Investigative Site | Szarvas | Hungary | 5540 | |
| 186 | Novartis Investigative Site | Szeged | Hungary | 6720 | |
| 187 | Novartis Investigative Site | Szeged | Hungary | 6722 | |
| 188 | Novartis Investigative Site | Szigetvar | Hungary | 7900 | |
| 189 | Novartis Investigative Site | Szombathely | Hungary | 9700 | |
| 190 | Novartis Investigative Site | New Delhi | Delhi | India | 110007 |
| 191 | Novartis Investigative Site | Ahmedabad | Gujarat | India | 380 008 |
| 192 | Novartis Investigative Site | Ahmedabad | Gujarat | India | 380016 |
| 193 | Novartis Investigative Site | Vadodara | Gujarat | India | 390021 |
| 194 | Novartis Investigative Site | Mysore | Karnataka | India | 570001 |
| 195 | Novartis Investigative Site | Kozhikode | Kerala | India | 673008 |
| 196 | Novartis Investigative Site | Mumbai | Maharashtra | India | 400601 |
| 197 | Novartis Investigative Site | Nagpur | Maharashtra | India | 440010 |
| 198 | Novartis Investigative Site | Nagpur | Maharashtra | India | 440012 |
| 199 | Novartis Investigative Site | Nagpur | Maharashtra | India | 440019 |
| 200 | Novartis Investigative Site | Pune | Maharashtra | India | 411007 |
| 201 | Novartis Investigative Site | Mohali | Punjab | India | 160 062 |
| 202 | Novartis Investigative Site | Jaipur | Rajasthan | India | 302001 |
| 203 | Novartis Investigative Site | Jaipur | Rajasthan | India | 302013 |
| 204 | Novartis Investigative Site | Jaipur | Rajasthan | India | 302020 |
| 205 | Novartis Investigative Site | Jaipur | Rajasthan | India | 302023 |
| 206 | Novartis Investigative Site | Hyderabad | Telangana | India | 500082 |
| 207 | Novartis Investigative Site | Lucknow | Uttar Pradesh | India | 226003 |
| 208 | Novartis Investigative Site | New Delhi | India | 110029 | |
| 209 | Novartis Investigative Site | Wilton | Cork | Ireland | |
| 210 | Novartis Investigative Site | County Limerick | Ireland | V94 F858 | |
| 211 | Novartis Investigative Site | Dublin | Ireland | DUBLIN 8 | |
| 212 | Novartis Investigative Site | Ichihara-city | Chiba | Japan | 299-0111 |
| 213 | Novartis Investigative Site | Fukuoka-city | Fukuoka | Japan | 819-8555 |
| 214 | Novartis Investigative Site | Kasuga-city | Fukuoka | Japan | 816-0813 |
| 215 | Novartis Investigative Site | Yanagawa-city | Fukuoka | Japan | 832-0059 |
| 216 | Novartis Investigative Site | Obihiro-city | Hokkaido | Japan | 080-0013 |
| 217 | Novartis Investigative Site | Himeji-city | Hyogo | Japan | 671-0102 |
| 218 | Novartis Investigative Site | Himeji-city | Hyogo | Japan | 672-8064 |
| 219 | Novartis Investigative Site | Naka-gun | Ibaraki | Japan | 319-1113 |
| 220 | Novartis Investigative Site | Atsugi-city | Kanagawa | Japan | 243-0034 |
| 221 | Novartis Investigative Site | Kawasaki-city | Kanagawa | Japan | 255 |
| 222 | Novartis Investigative Site | Yokohama-city | Kanagawa | Japan | 223-0059 |
| 223 | Novartis Investigative Site | Yokohama-city | Kanagawa | Japan | 231-8682 |
| 224 | Novartis Investigative Site | Yokohama-city | Kanagawa | Japan | 236-0004 |
| 225 | Novartis Investigative Site | Yokohama | Kanagawa | Japan | 232-0064 |
| 226 | Novartis Investigative Site | Sendai-city | Miyagi | Japan | 980-0871 |
| 227 | Novartis Investigative Site | Okayama-city | Okayama | Japan | 702-8055 |
| 228 | Novartis Investigative Site | Kishiwada-city | Osaka | Japan | 596-8501 |
| 229 | Novartis Investigative Site | Osaka city | Osaka | Japan | 530 0001 |
| 230 | Novartis Investigative Site | Takatsuki-city | Osaka | Japan | 569-1192 |
| 231 | Novartis Investigative Site | Toyonaka-city | Osaka | Japan | |
| 232 | Novartis Investigative Site | Yao-city | Osaka | Japan | 581-0011 |
| 233 | Novartis Investigative Site | Koshigaya-city | Saitama | Japan | 343-8555 |
| 234 | Novartis Investigative Site | Tokyo | Shibuya Ku | Japan | 150 0013 |
| 235 | Novartis Investigative Site | Chuo ku | Tokyo | Japan | 103 0027 |
| 236 | Novartis Investigative Site | Chuou-ku | Tokyo | Japan | 103-0028 |
| 237 | Novartis Investigative Site | Itabashi-ku | Tokyo | Japan | 173-8610 |
| 238 | Novartis Investigative Site | Setagaya-Ku | Tokyo | Japan | 157-0072 |
| 239 | Novartis Investigative Site | Shinjuku-ku | Tokyo | Japan | 162-0053 |
| 240 | Novartis Investigative Site | Shinjuku-ku | Tokyo | Japan | 169-0073 |
| 241 | Novartis Investigative Site | Toshima ku | Tokyo | Japan | 170 0003 |
| 242 | Novartis Investigative Site | Toshima-ku | Tokyo | Japan | 171-0014 |
| 243 | Novartis Investigative Site | Cheongju si | Chungcheongbuk Do | Korea, Republic of | 28644 |
| 244 | Novartis Investigative Site | Wonju | Gangwon-do | Korea, Republic of | 26427 |
| 245 | Novartis Investigative Site | Bundang Gu | Gyeonggi Do | Korea, Republic of | 13620 |
| 246 | Novartis Investigative Site | Bucheon-Si | Gyeonggi-Do | Korea, Republic of | 14584 |
| 247 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 03312 |
| 248 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 08308 |
| 249 | Novartis Investigative Site | Seoul | Seocho Gu | Korea, Republic of | 06591 |
| 250 | Novartis Investigative Site | Incheon | Korea, Republic of | 403-720 | |
| 251 | Novartis Investigative Site | Riga | LV | Latvia | 1011 |
| 252 | Novartis Investigative Site | Daugavpils | Latvia | LV-5401 | |
| 253 | Novartis Investigative Site | Riga | Latvia | LV 1002 | |
| 254 | Novartis Investigative Site | Riga | Latvia | LV-1001 | |
| 255 | Novartis Investigative Site | Kaunas | LTU | Lithuania | LT-48259 |
| 256 | Novartis Investigative Site | Kaunas | Lithuania | LT-49449 | |
| 257 | Novartis Investigative Site | Siauliai | Lithuania | LT-76231 | |
| 258 | Novartis Investigative Site | Utena | Lithuania | LT-28151 | |
| 259 | Novartis Investigative Site | Vilnius | Lithuania | LT-09108 | |
| 260 | Novartis Investigative Site | Mexicali | Baja California | Mexico | 21100 |
| 261 | Novartis Investigative Site | Ciudad de Mexico | Distrito Federal | Mexico | 06700 |
| 262 | Novartis Investigative Site | Mexico | Distrito Federal | Mexico | 14050 |
| 263 | Novartis Investigative Site | Mexico | Mexico | 07760 | |
| 264 | Novartis Investigative Site | Lodz | POL | Poland | 91-110 |
| 265 | Novartis Investigative Site | Wejherowo | POL | Poland | 84-200 |
| 266 | Novartis Investigative Site | Aleksandrow Odzki | Poland | 95-070 | |
| 267 | Novartis Investigative Site | Biaystok | Poland | 15-430 | |
| 268 | Novartis Investigative Site | Bielsko-Biala | Poland | 43-300 | |
| 269 | Novartis Investigative Site | Elblag | Poland | 82-300 | |
| 270 | Novartis Investigative Site | Inowroclaw | Poland | 88-100 | |
| 271 | Novartis Investigative Site | Katowice | Poland | 40 085 | |
| 272 | Novartis Investigative Site | Krakow | Poland | 30033 | |
| 273 | Novartis Investigative Site | Lodz | Poland | 90-302 | |
| 274 | Novartis Investigative Site | Ostrow Wielkopolski | Poland | 63-400 | |
| 275 | Novartis Investigative Site | Sopot | Poland | 81-741 | |
| 276 | Novartis Investigative Site | Warsaw | Poland | 01518 | |
| 277 | Novartis Investigative Site | Zawadzkie | Poland | 47-120 | |
| 278 | Novartis Investigative Site | Iasi | Jud Iasi | Romania | 700732 |
| 279 | Novartis Investigative Site | Constanta | Jud. Constanta | Romania | 900002 |
| 280 | Novartis Investigative Site | Craiova | Jud.Dolj | Romania | 200341 |
| 281 | Novartis Investigative Site | Bucharest | ROM | Romania | 12071 |
| 282 | Novartis Investigative Site | Craiova | ROM | Romania | 000000 |
| 283 | Novartis Investigative Site | Craiova | ROM | Romania | 200712 |
| 284 | Novartis Investigative Site | Deva | ROM | Romania | 330084 |
| 285 | Novartis Investigative Site | Timisoara | ROM | Romania | 300298 |
| 286 | Novartis Investigative Site | Timisoara | Timis | Romania | 300310 |
| 287 | Novartis Investigative Site | Arad | Romania | 310013 | |
| 288 | Novartis Investigative Site | Bacau | Romania | 600114 | |
| 289 | Novartis Investigative Site | Bragadiru | Romania | 077025 | |
| 290 | Novartis Investigative Site | Braila | Romania | 810003 | |
| 291 | Novartis Investigative Site | Brasov | Romania | 500051 | |
| 292 | Novartis Investigative Site | Bucharest | Romania | 020125 | |
| 293 | Novartis Investigative Site | Bucuresti | Romania | 012363 | |
| 294 | Novartis Investigative Site | Bucuresti | Romania | 050554 | |
| 295 | Novartis Investigative Site | Cluj Napoca | Romania | 400275 | |
| 296 | Novartis Investigative Site | Cluj Napoca | Romania | 400371 | |
| 297 | Novartis Investigative Site | Cluj-Napoca | Romania | 400371 | |
| 298 | Novartis Investigative Site | Codlea | Romania | 505100 | |
| 299 | Novartis Investigative Site | Craiova | Romania | 200515 | |
| 300 | Novartis Investigative Site | Ramnicu Valcea | Romania | 240564 | |
| 301 | Novartis Investigative Site | Suceava | Romania | 720284 | |
| 302 | Novartis Investigative Site | Targu Mures | Romania | 540072 | |
| 303 | Novartis Investigative Site | Chelyabinsk | Russian Federation | 454021 | |
| 304 | Novartis Investigative Site | Chelyabinsk | Russian Federation | 454076 | |
| 305 | Novartis Investigative Site | Kazan | Russian Federation | 420012 | |
| 306 | Novartis Investigative Site | Krasnoyarsk | Russian Federation | 660022 | |
| 307 | Novartis Investigative Site | Moscow | Russian Federation | 105275 | |
| 308 | Novartis Investigative Site | Moscow | Russian Federation | 119192 | |
| 309 | Novartis Investigative Site | N.Novgorod | Russian Federation | 603126 | |
| 310 | Novartis Investigative Site | Novosibirsk | Russian Federation | 630047 | |
| 311 | Novartis Investigative Site | Novosibirsk | Russian Federation | 630099 | |
| 312 | Novartis Investigative Site | Penza | Russian Federation | 440067 | |
| 313 | Novartis Investigative Site | Petrozavodsk | Russian Federation | 185019 | |
| 314 | Novartis Investigative Site | Pyatigorsk | Russian Federation | 357538 | |
| 315 | Novartis Investigative Site | Ryazan | Russian Federation | 390026 | |
| 316 | Novartis Investigative Site | Ryazan | Russian Federation | 390039 | |
| 317 | Novartis Investigative Site | Saint Petersburg | Russian Federation | 191123 | |
| 318 | Novartis Investigative Site | Saint-Petersburg | Russian Federation | 192257 | |
| 319 | Novartis Investigative Site | Saratov | Russian Federation | 410012 | |
| 320 | Novartis Investigative Site | Saratov | Russian Federation | 410053 | |
| 321 | Novartis Investigative Site | Smolensk | Russian Federation | 214006 | |
| 322 | Novartis Investigative Site | Smolensk | Russian Federation | 214031 | |
| 323 | Novartis Investigative Site | St Petersburg | Russian Federation | 190044 | |
| 324 | Novartis Investigative Site | St Petersburg | Russian Federation | 191015 | |
| 325 | Novartis Investigative Site | St Petersburg | Russian Federation | 191180 | |
| 326 | Novartis Investigative Site | St Petersburg | Russian Federation | 194223 | |
| 327 | Novartis Investigative Site | St Petersburg | Russian Federation | 194291 | |
| 328 | Novartis Investigative Site | St Petersburg | Russian Federation | 194354 | |
| 329 | Novartis Investigative Site | St-Petersburg | Russian Federation | 193312 | |
| 330 | Novartis Investigative Site | St-Petersburg | Russian Federation | 194291 | |
| 331 | Novartis Investigative Site | St.Petersburg | Russian Federation | 196240 | |
| 332 | Novartis Investigative Site | Stavropol | Russian Federation | 355000 | |
| 333 | Novartis Investigative Site | Volgograd | Russian Federation | 400120 | |
| 334 | Novartis Investigative Site | Vologodonsk | Russian Federation | 347382 | |
| 335 | Novartis Investigative Site | Yaroslavl | Russian Federation | 150000 | |
| 336 | Novartis Investigative Site | Yaroslavl | Russian Federation | 150003 | |
| 337 | Novartis Investigative Site | Yaroslavl | Russian Federation | 150023 | |
| 338 | Novartis Investigative Site | Yaroslavl | Russian Federation | 150040 | |
| 339 | Novartis Investigative Site | Yekaterinburg | Russian Federation | 620137 | |
| 340 | Novartis Investigative Site | Belgrade | Serbia | 11000 | |
| 341 | Novartis Investigative Site | Beograd | Serbia | 11000 | |
| 342 | Novartis Investigative Site | Kragujevac | Serbia | 34000 | |
| 343 | Novartis Investigative Site | Nis | Serbia | 18000 | |
| 344 | Novartis Investigative Site | Sremska Kamenica | Serbia | 21204 | |
| 345 | Novartis Investigative Site | Bardejov | Slovak Republic | Slovakia | 085 01 |
| 346 | Novartis Investigative Site | Bojnice | Slovak Republic | Slovakia | 972 01 |
| 347 | Novartis Investigative Site | Bratislava | Slovak Republic | Slovakia | 83103 |
| 348 | Novartis Investigative Site | Humenne | Slovak Republic | Slovakia | 066 01 |
| 349 | Novartis Investigative Site | Kosice | Slovak Republic | Slovakia | 040 01 |
| 350 | Novartis Investigative Site | Nitra | Slovak Republic | Slovakia | 949 01 |
| 351 | Novartis Investigative Site | Skalica | Slovak Republic | Slovakia | 90901 |
| 352 | Novartis Investigative Site | Spisska Nova Ves | Slovak Republic | Slovakia | 052 01 |
| 353 | Novartis Investigative Site | Stropkov | Slovak Republic | Slovakia | 09101 |
| 354 | Novartis Investigative Site | Surany | Slovak Republic | Slovakia | 942 01 |
| 355 | Novartis Investigative Site | Velky Meder | Slovak Republic | Slovakia | 94201 |
| 356 | Novartis Investigative Site | Námestovo | Slovensko | Slovakia | 02901 |
| 357 | Novartis Investigative Site | Poprad | SVK | Slovakia | 058 01 |
| 358 | Novartis Investigative Site | Bardejov | Slovakia | 085 01 | |
| 359 | Novartis Investigative Site | Bratislava | Slovakia | 85101 | |
| 360 | Novartis Investigative Site | Cadca | Slovakia | 022 01 | |
| 361 | Novartis Investigative Site | Ilava | Slovakia | 1901 | |
| 362 | Novartis Investigative Site | Komarno | Slovakia | 945 01 | |
| 363 | Novartis Investigative Site | Kosice | Slovakia | 040 01 | |
| 364 | Novartis Investigative Site | Kosice | Slovakia | 04001 | |
| 365 | Novartis Investigative Site | Kralovsky Chlmec | Slovakia | 077 01 | |
| 366 | Novartis Investigative Site | Levice | Slovakia | 034 01 | |
| 367 | Novartis Investigative Site | Liptovsky Mikulas | Slovakia | 031 23 | |
| 368 | Novartis Investigative Site | Presov | Slovakia | 080 01 | |
| 369 | Novartis Investigative Site | Prievidza | Slovakia | 97101 | |
| 370 | Novartis Investigative Site | Topolcany | Slovakia | 95501 | |
| 371 | Novartis Investigative Site | Zilina | Slovakia | 010 01 | |
| 372 | Novartis Investigative Site | Zilina | Slovakia | 01001 | |
| 373 | Novartis Investigative Site | Berea | Durban | South Africa | 4001 |
| 374 | Novartis Investigative Site | Panorama | Western Cape | South Africa | 7500 |
| 375 | Novartis Investigative Site | Belleville | South Africa | 7530 | |
| 376 | Novartis Investigative Site | Cape Town | South Africa | 7531 | |
| 377 | Novartis Investigative Site | Cape Town | South Africa | 7700 | |
| 378 | Novartis Investigative Site | Cape Town | South Africa | 7925 | |
| 379 | Novartis Investigative Site | Fowey | Cornwall | United Kingdom | PL23 1DT |
| 380 | Novartis Investigative Site | Liskeard | Cornwall | United Kingdom | PL14 3XA |
| 381 | Novartis Investigative Site | Torpoint | Cornwall | United Kingdom | PL11 2TB |
| 382 | Novartis Investigative Site | Faringdon | Oxfordshire | United Kingdom | SN7 7YU |
| 383 | Novartis Investigative Site | Bristol | South Gloucestershire | United Kingdom | BS37 4AX |
| 384 | Novartis Investigative Site | Blackpool | United Kingdom | FY5 3LF | |
| 385 | Novartis Investigative Site | Denbighshire | United Kingdom | LL181DA | |
| 386 | Novartis Investigative Site | Glasgow | United Kingdom | G20 0XA | |
| 387 | Novartis Investigative Site | London | United Kingdom | EC14 7BE | |
| 388 | Novartis Investigative Site | London | United Kingdom | SE5 8AD | |
| 389 | Novartis Investigative Site | Rotherham | United Kingdom | S65 1DA | |
| 390 | Novartis Investigative Site | Wiltshire | United Kingdom | SN15 2SB |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02554786
Other Study ID Numbers:
- CQVM149B2301
- 2015-002529-21
First Posted:
Sep 18, 2015
Last Update Posted:
Mar 5, 2020
Last Verified:
Feb 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in 316 investigative sites in 24 countries from 29 Dec 2015 to 28 Jun 2019. |
|---|---|
| Pre-assignment Detail | 3890 participants were screened of which 2216 were randomized to 1 of the 5 treatment groups with a randomization ratio of 1:1:1:1:1. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered once daily (o.d.) via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | Mometasone furoate (MF) 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Period Title: Overall Study | |||||
| STARTED | 445 | 439 | 442 | 444 | 446 |
| COMPLETED | 410 | 413 | 412 | 403 | 416 |
| NOT COMPLETED | 35 | 26 | 30 | 41 | 30 |
Baseline Characteristics
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. | Total of all reporting groups |
| Overall Participants | 445 | 439 | 442 | 444 | 446 | 2216 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
47.1
(14.56)
|
47.4
(14.76)
|
47.5
(14.99)
|
48.7
(14.98)
|
48.9
(14.59)
|
47.9
(14.78)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
262
58.9%
|
253
57.6%
|
250
56.6%
|
272
61.3%
|
256
57.4%
|
1293
58.3%
|
| Male |
183
41.1%
|
186
42.4%
|
192
43.4%
|
172
38.7%
|
190
42.6%
|
923
41.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| Caucasian |
313
70.3%
|
311
70.8%
|
318
71.9%
|
312
70.3%
|
305
68.4%
|
1559
70.4%
|
| Black |
5
1.1%
|
2
0.5%
|
4
0.9%
|
8
1.8%
|
4
0.9%
|
23
1%
|
| Asian |
97
21.8%
|
98
22.3%
|
98
22.2%
|
98
22.1%
|
102
22.9%
|
493
22.2%
|
| Native American |
13
2.9%
|
14
3.2%
|
11
2.5%
|
18
4.1%
|
12
2.7%
|
68
3.1%
|
| Pacific Islander |
1
0.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0%
|
| Other |
16
3.6%
|
14
3.2%
|
11
2.5%
|
8
1.8%
|
23
5.2%
|
72
3.2%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| Hispanic Or Latino |
21
4.7%
|
17
3.9%
|
14
3.2%
|
22
5%
|
15
3.4%
|
89
4%
|
| East Asian |
52
11.7%
|
48
10.9%
|
51
11.5%
|
55
12.4%
|
53
11.9%
|
259
11.7%
|
| Southeast Asian |
38
8.5%
|
40
9.1%
|
42
9.5%
|
38
8.6%
|
42
9.4%
|
200
9%
|
| South Asian |
3
0.7%
|
3
0.7%
|
2
0.5%
|
3
0.7%
|
3
0.7%
|
14
0.6%
|
| Russian |
79
17.8%
|
79
18%
|
64
14.5%
|
62
14%
|
65
14.6%
|
349
15.7%
|
| Mixed ethnicity |
10
2.2%
|
10
2.3%
|
9
2%
|
5
1.1%
|
15
3.4%
|
49
2.2%
|
| Not reported |
12
2.7%
|
4
0.9%
|
12
2.7%
|
5
1.1%
|
9
2%
|
42
1.9%
|
| Unknown |
12
2.7%
|
13
3%
|
6
1.4%
|
15
3.4%
|
17
3.8%
|
63
2.8%
|
| Other |
218
49%
|
225
51.3%
|
242
54.8%
|
239
53.8%
|
227
50.9%
|
1151
51.9%
|
Outcome Measures
| Title | Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26 |
|---|---|
| Description | Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. |
| Time Frame | 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 395 | 389 | 372 | 376 | 391 |
| Least Squares Mean (Standard Error) [litre (L)] |
2.383
(0.0159)
|
2.387
(0.0160)
|
2.250
(0.0162)
|
2.176
(0.0162)
|
2.346
(0.0160)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Model for Repeated Measures (MMRM) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square mean (LS Mean) |
| Estimated Value | 0.132 | |
| Confidence Interval |
(2-Sided) 95% 0.088 to 0.176 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0223 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.211 | |
| Confidence Interval |
(2-Sided) 95% 0.167 to 0.255 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0224 |
|
| Estimation Comments | ||
| Title | Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52 |
|---|---|
| Description | The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway calibre (FEV1 % predicted). All 7 questions of the ACQ-7 were equally weighted. Items 1-5 were scored along a 7-point response scale, where 0 = totally controlled and 6 = severely uncontrolled. Item 6 is scored between 0 = no rescue medication and 6 = More than 16 puffs/inhalations most days. The 7th item was scored by the investigator based on the FEV1 % predicted from the masterscope at the site (i.e., Score = 0 means > 95% of predicted FEV1, 1 = 90 - 95%, 2 = 80 - 89%, 3 = 70 - 79%, 4 = 60 - 69%, 5 = 50 - 59%, and Score = 6 means < 50% of predicted FEV1). The total score was calculated as the mean of all questions. |
| Time Frame | Weeks 4, 12, 26 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents the number of participants with data at respective visit |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 429 | 427 | 431 | 428 | 439 |
| Week 4 |
1.486
(0.0337)
|
1.533
(0.0338)
|
1.659
(0.0338)
|
1.730
(0.0337)
|
1.541
(0.0335)
|
| Week 12 |
1.394
(0.0347)
|
1.377
(0.0348)
|
1.523
(0.0348)
|
1.625
(0.0350)
|
1.445
(0.0345)
|
| Week 26 |
1.267
(0.0350)
|
1.261
(0.0350)
|
1.439
(0.0352)
|
1.509
(0.0354)
|
1.322
(0.0349)
|
| Week 52 |
1.231
(0.0358)
|
1.183
(0.0356)
|
1.373
(0.0359)
|
1.449
(0.0361)
|
1.221
(0.0354)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.172 | |
| Confidence Interval |
(2-Sided) 95% -0.254 to -0.091 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0415 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.196 | |
| Confidence Interval |
(2-Sided) 95% -0.278 to -0.115 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0416 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.186 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.055 | |
| Confidence Interval |
(2-Sided) 95% -0.136 to 0.026 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0414 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, QMF149 150/160 μg, MF 800 μg, MF 400 μg |
|---|---|---|
| Comments | Week 4: The comparison of QMF149 vs. MF was based on combined effects of QMF149 150/160 & 150/320 μg and MF 400 & 800 μg derived by weighting treatment groups equally. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.184 | |
| Confidence Interval |
(2-Sided) 95% -0.242 to -0.127 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0294 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.129 | |
| Confidence Interval |
(2-Sided) 95% -0.214 to -0.044 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0431 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.248 | |
| Confidence Interval |
(2-Sided) 95% -0.333 to -0.162 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0435 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.232 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.052 | |
| Confidence Interval |
(2-Sided) 95% -0.136 to 0.033 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0431 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, QMF149 150/160 μg, MF 800 μg, MF 400 μg |
|---|---|---|
| Comments | Week 12: The comparison of QMF149 vs. MF was based on combined effects of QMF149 150/160 & 150/320 μg and MF 400 & 800 μg derived by weighting treatment groups equally. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.188 | |
| Confidence Interval |
(2-Sided) 95% -0.248 to -0.128 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0307 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.171 | |
| Confidence Interval |
(2-Sided) 95% -0.257 to -0.086 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0437 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.248 | |
| Confidence Interval |
(2-Sided) 95% -0.334 to -0.162 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0439 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.214 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.054 | |
| Confidence Interval |
(2-Sided) 95% -0.140 to 0.031 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0437 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, QMF149 150/160 μg, MF 800 μg, MF 400 μg |
|---|---|---|
| Comments | Week 26: The comparison of QMF149 vs. MF was based on combined effects of QMF149 150/160 & 150/320 μg and MF 400 & 800 μg derived by weighting treatment groups equally. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.209 | |
| Confidence Interval |
(2-Sided) 95% -0.270 to -0.149 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0310 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 52 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.141 | |
| Confidence Interval |
(2-Sided) 95% -0.229 to -0.053 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0449 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 52 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.266 | |
| Confidence Interval |
(2-Sided) 95% -0.354 to -0.177 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.045 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 52 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.824 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.078 to 0.098 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0447 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, QMF149 150/160 μg, MF 800 μg, MF 400 μg |
|---|---|---|
| Comments | Week 52: The comparison of QMF149 vs. MF was based on combined effects of QMF149 150/160 & 150/320 μg and MF 400 & 800 μg derived by weighting treatment groups equally. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.203 | |
| Confidence Interval |
(2-Sided) 95% -0.266 to -0.141 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0318 |
|
| Estimation Comments | ||
| Title | Trough FEV1 at Week 52 |
|---|---|
| Description | Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. |
| Time Frame | Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 372 | 383 | 364 | 369 | 382 |
| Least Squares Mean (Standard Error) [L] |
2.386
(0.0168)
|
2.357
(0.0167)
|
2.249
(0.0170)
|
2.148
(0.0170)
|
2.338
(0.0167)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.136 | |
| Confidence Interval |
(2-Sided) 95% 0.090 to 0.183 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0235 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.209 | |
| Confidence Interval |
(2-Sided) 95% 0.163 to 0.255 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0235 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.04 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.048 | |
| Confidence Interval |
(2-Sided) 95% 0.002 to 0.094 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0234 |
|
| Estimation Comments | ||
| Title | Pre-dose FEV1 at Weeks 4 and 12 |
|---|---|
| Description | Pre-dose trough FEV1 is defined as average of the two FEV1 measurements taken 45 min and 15 min pre evening dose. It was assessed by performing spirometric assessment. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. |
| Time Frame | Weeks 4 (Day 30) and 12 (Day 86) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents the number of participants with data at respective visit. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol /Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d via Twisthaler® in the evening | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 430 | 427 | 430 | 427 | 439 |
| Day 30 |
2.369
(0.0141)
|
2.367
(0.0142)
|
2.237
(0.0143)
|
2.171
(0.0143)
|
0.2333
(0.0141)
|
| Day 86 |
2.368
(0.0148)
|
2.361
(0.0148)
|
2.245
(0.0148)
|
2.177
(0.0149)
|
2.330
(0.0146)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 30 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.132 | |
| Confidence Interval |
(2-Sided) 95% 0.094 to 0.170 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0193 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 30 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.196 | |
| Confidence Interval |
(2-Sided) 95% 0.158 to 0.234 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0194 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 30 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.064 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.035 | |
| Confidence Interval |
(2-Sided) 95% -0.002 to 0.073 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0192 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 86 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.122 | |
| Confidence Interval |
(2-Sided) 95% 0.083 to 0.162 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0201 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 86 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.184 | |
| Confidence Interval |
(2-Sided) 95% 0.144 to 0.224 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0202 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 86 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.063 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.037 | |
| Confidence Interval |
(2-Sided) 95% -0.002 to 0.076 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.02 |
|
| Estimation Comments | ||
| Title | Post Dose FEV1 (5 Minutes-1 Hour) |
|---|---|
| Description | Post-dose FEV1 measurements were analyzed at 5 minutes, 15 minutes, 30 minutes and 1 hour. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. |
| Time Frame | Up to Week 52 (Day 364) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents the number of participants with data at respective time point. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 441 | 434 | 438 | 438 | 442 |
| Day 1: 5 minutes |
2.279
(0.0084)
|
2.270
(0.0085)
|
2.138
(0.0085)
|
2.118
(0.0084)
|
2.224
(0.0084)
|
| Day 1: 15 minutes |
2.321
(0.0088)
|
2.312
(0.0089)
|
2.159
(0.0089)
|
2.137
(0.0089)
|
2.278
(0.0088)
|
| Day 1: 30 minutes |
2.338
(0.0095)
|
2.326
(0.0096)
|
2.162
(0.0096)
|
2.141
(0.0095)
|
2.310
(0.0095)
|
| Day 1: 1 hour |
2.343
(0.0100)
|
2.347
(0.0101)
|
2.166
(0.0101)
|
2.142
(0.0100)
|
2.337
(0.0100)
|
| Day 30: 5 minutes |
2.413
(0.0142)
|
2.406
(0.0144)
|
2.224
(0.0145)
|
2.174
(0.0145)
|
2.360
(0.0142)
|
| Day 30: 30 minutes |
2.432
(0.0143)
|
2.426
(0.0145)
|
2.238
(0.0146)
|
2.174
(0.0146)
|
2.389
(0.0143)
|
| Day 30: 1 hour |
2.448
(0.0145)
|
2.440
(0.0146)
|
2.257
(0.0147)
|
2.183
(0.0148)
|
2.411
(0.0144)
|
| Day 86:5 minutes |
2.411
(0.0150)
|
2.409
(0.0150)
|
2.248
(0.0150)
|
2.178
(0.0153)
|
2.356
(0.0148)
|
| Day 86: 30 minutes |
2.436
(0.0149)
|
2.431
(0.0149)
|
2.257
(0.0149)
|
2.179
(0.0152)
|
2.398
(0.0147)
|
| Day 86:1 hour |
2.456
(0.0151)
|
2.436
(0.0151)
|
2.269
(0.0151)
|
2.188
(0.0154)
|
2.413
(0.0149)
|
| Day 183: 5 minutes |
2.403
(0.0160)
|
2.406
(0.0161)
|
2.240
(0.0162)
|
2.163
(0.0164)
|
2.359
(0.0160)
|
| Day 183: 30 minutes |
2.426
(0.0163)
|
2.427
(0.0164)
|
2.250
(0.0165)
|
2.168
(0.0167)
|
2.386
(0.0163)
|
| Day 183: 1 hour |
2.432
(0.0161)
|
2.423
(0.0162)
|
2.253
(0.0163)
|
2.165
(0.0165)
|
2.393
(0.0161)
|
| Day 364: 5 minutes |
2.384
(0.0172)
|
2.379
(0.0169)
|
2.245
(0.0172)
|
2.130
(0.0173)
|
2.358
(0.0168)
|
| Day 364: 30 minutes |
2.408
(0.0171)
|
2.399
(0.0169)
|
2.253
(0.0172)
|
2.135
(0.0172)
|
2.377
(0.0167)
|
| Day 364:1 hour |
2.414
(0.0175)
|
2.390
(0.0172)
|
2.251
(0.0175)
|
2.128
(0.0176)
|
2.383
(0.0171)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 1: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.142 | |
| Confidence Interval |
(2-Sided) 95% 0.119 to 0.164 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0116 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 1: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.152 | |
| Confidence Interval |
(2-Sided) 95% 0.129 to 0.175 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0116 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 1: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.055 | |
| Confidence Interval |
(2-Sided) 95% 0.032 to 0.078 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0116 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 1: 15 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.162 | |
| Confidence Interval |
(2-Sided) 95% 0.138 to 0.186 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0122 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 1: 15 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean |
| Estimated Value | 0.174 | |
| Confidence Interval |
(2-Sided) 95% 0.150 to 0.198 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0123 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day1: 15 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.044 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.068 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0122 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 1: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.175 | |
| Confidence Interval |
(2-Sided) 95% 0.149 to 0.201 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0132 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 1: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.185 | |
| Confidence Interval |
(2-Sided) 95% 0.159 to 0.211 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0132 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 1: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.027 | |
| Confidence Interval |
(2-Sided) 95% 0.001 to 0.053 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0132 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 1: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.178 | |
| Confidence Interval |
(2-Sided) 95% 0.150 to 0.205 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0139 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 1: 1hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.205 | |
| Confidence Interval |
(2-Sided) 95% 0.177 to 0.232 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0139 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 1: 1hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.632 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.007 | |
| Confidence Interval |
(2-Sided) 95% -0.021 to 0.034 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0139 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 30: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.189 | |
| Confidence Interval |
(2-Sided) 95% 0.151 to 0.226 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0192 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 30: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.232 | |
| Confidence Interval |
(2-Sided) 95% 0.194 to 0.270 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0194 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 30: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.053 | |
| Confidence Interval |
(2-Sided) 95% 0.016 to 0.091 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0191 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 30: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.194 | |
| Confidence Interval |
(2-Sided) 95% 0.156 to 0.232 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0194 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 30: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.253 | |
| Confidence Interval |
(2-Sided) 95% 0.214 to 0.291 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0196 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 30: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.043 | |
| Confidence Interval |
(2-Sided) 95% 0.005 to 0.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0192 |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 30: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.190 | |
| Confidence Interval |
(2-Sided) 95% 0.152 to 0.229 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0196 |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 30: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.258 | |
| Confidence Interval |
(2-Sided) 95% 0.219 to 0.296 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0198 |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 30: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.059 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.037 | |
| Confidence Interval |
(2-Sided) 95% -0.001 to 0.075 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0194 |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 86: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.163 | |
| Confidence Interval |
(2-Sided) 95% 0.123 to 0.203 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0204 |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 86: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.231 | |
| Confidence Interval |
(2-Sided) 95% 0.191 to 0.271 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0206 |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 86: 5minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.055 | |
| Confidence Interval |
(2-Sided) 95% 0.015 to 0.095 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0203 |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 86: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.180 | |
| Confidence Interval |
(2-Sided) 95% 0.140 to 0.219 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0203 |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 86: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.252 | |
| Confidence Interval |
(2-Sided) 95% 0.211 to 0.292 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0205 |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 86: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.057 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.038 | |
| Confidence Interval |
(2-Sided) 95% -0.001 to 0.078 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0202 |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 86: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.187 | |
| Confidence Interval |
(2-Sided) 95% 0.147 to 0.227 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0205 |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 86: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.249 | |
| Confidence Interval |
(2-Sided) 95% 0.208 to 0.289 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0208 |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 86: 1hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.043 | |
| Confidence Interval |
(2-Sided) 95% 0.003 to 0.083 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0205 |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 183: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.163 | |
| Confidence Interval |
(2-Sided) 95% 0.121 to 0.206 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0217 |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 183: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.243 | |
| Confidence Interval |
(2-Sided) 95% 0.200 to 0.286 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0219 |
|
| Estimation Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 183: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.041 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.044 | |
| Confidence Interval |
(2-Sided) 95% 0.002 to 0.087 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0216 |
|
| Estimation Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 183: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.176 | |
| Confidence Interval |
(2-Sided) 95% 0.133 to 0.220 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0222 |
|
| Estimation Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 183: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.259 | |
| Confidence Interval |
(2-Sided) 95% 0.215 to 0.303 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0224 |
|
| Estimation Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 183: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.071 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.003 to 0.083 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0221 |
|
| Estimation Comments | ||
Statistical Analysis 37
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 183: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.180 | |
| Confidence Interval |
(2-Sided) 95% 0.137 to 0.223 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0219 |
|
| Estimation Comments | ||
Statistical Analysis 38
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 183: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.259 | |
| Confidence Interval |
(2-Sided) 95% 0.215 to 0.302 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0222 |
|
| Estimation Comments | ||
Statistical Analysis 39
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 183: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.071 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.039 | |
| Confidence Interval |
(2-Sided) 95% -0.003 to 0.082 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0218 |
|
| Estimation Comments | ||
Statistical Analysis 40
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 364: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.139 | |
| Confidence Interval |
(2-Sided) 95% 0.094 to 0.184 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0229 |
|
| Estimation Comments | ||
Statistical Analysis 41
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 364: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.249 | |
| Confidence Interval |
(2-Sided) 95% 0.205 to 0.294 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0228 |
|
| Estimation Comments | ||
Statistical Analysis 42
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 364: 5 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.244 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.026 | |
| Confidence Interval |
(2-Sided) 95% -0.018 to 0.071 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0227 |
|
| Estimation Comments | ||
Statistical Analysis 43
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 364: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.155 | |
| Confidence Interval |
(2-Sided) 95% 0.110 to 0.200 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0228 |
|
| Estimation Comments | ||
Statistical Analysis 44
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 364: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.264 | |
| Confidence Interval |
(2-Sided) 95% 0.219 to 0.308 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0227 |
|
| Estimation Comments | ||
Statistical Analysis 45
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 364: 30 minutes | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.162 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.032 | |
| Confidence Interval |
(2-Sided) 95% -0.013 to 0.076 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0226 |
|
| Estimation Comments | ||
Statistical Analysis 46
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 364: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.163 | |
| Confidence Interval |
(2-Sided) 95% 0.117 to 0.209 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0234 |
|
| Estimation Comments | ||
Statistical Analysis 47
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 364: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.262 | |
| Confidence Interval |
(2-Sided) 95% 0.216 to 0.308 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0232 |
|
| Estimation Comments | ||
Statistical Analysis 48
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 364: 1 hour | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.182 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.031 | |
| Confidence Interval |
(2-Sided) 95% -0.014 to 0.076 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0231 |
|
| Estimation Comments | ||
| Title | Trough Forced Vital Capacity (FVC) |
|---|---|
| Description | FVC is the total amount of air exhaled during the FEV test. Trough FVC is defined as average of the two FVC measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. It was assessed by performing spirometric assessment. |
| Time Frame | Up to Week 52 (Day 365) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents the number of participants with data at respective visit. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 439 | 433 | 436 | 441 | 441 |
| Day 2 |
3.342
(0.0173)
|
3.342
(0.0174)
|
3.256
(0.0177)
|
3.203
(0.0173)
|
3.344
(0.0176)
|
| Day 184 |
3.372
(0.0179)
|
3.387
(0.0180)
|
3.322
(0.0183)
|
3.246
(0.0182)
|
3.355
(0.0180)
|
| Day 365 |
3.394
(0.0182)
|
3.364
(0.0181)
|
3.319
(0.0184)
|
3.218
(0.0183)
|
3.358
(0.0182)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.086 | |
| Confidence Interval |
(2-Sided) 95% 0.040 to 0.133 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.139 | |
| Confidence Interval |
(2-Sided) 95% 0.093 to 0.185 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0235 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.927 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.002 | |
| Confidence Interval |
(2-Sided) 95% -0.049 to 0.044 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 184 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.044 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.050 | |
| Confidence Interval |
(2-Sided) 95% 0.001 to 0.098 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0246 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 184 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.141 | |
| Confidence Interval |
(2-Sided) 95% 0.093 to 0.190 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0246 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 184 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.490 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.017 | |
| Confidence Interval |
(2-Sided) 95% -0.031 to 0.065 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0244 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.076 | |
| Confidence Interval |
(2-Sided) 95% 0.027 to 0.125 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0249 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.146 | |
| Confidence Interval |
(2-Sided) 95% 0.098 to 0.195 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0248 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.143 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.036 | |
| Confidence Interval |
(2-Sided) 95% -0.012 to 0.085 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0248 |
|
| Estimation Comments | ||
| Title | Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75) |
|---|---|
| Description | FEF is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration. Trough FEF25-75% is defined as average of the two FEF25-75% measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. It was assessed by performing spirometric assessment. |
| Time Frame | Up to Week 52 (Day 365) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents the number of participants with data at respective visit. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 439 | 433 | 436 | 441 | 441 |
| Day 2 |
1.644
(0.0186)
|
1.617
(0.0187)
|
1.455
(0.0191)
|
1.406
(0.0186)
|
1.662
(0.0189)
|
| Day 184 |
1.775
(0.0249)
|
1.738
(0.0250)
|
1.546
(0.0253)
|
1.473
(0.0254)
|
1.692
(0.0250)
|
| Day 365 |
1.745
(0.0259)
|
1.686
(0.0257)
|
1.530
(0.0261)
|
1.440
(0.0261)
|
1.692
(0.0258)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.189 | |
| Confidence Interval |
(2-Sided) 95% 0.139 to 0.238 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0253 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.210 | |
| Confidence Interval |
(2-Sided) 95% 0.161 to 0.259 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.025 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.475 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.018 | |
| Confidence Interval |
(2-Sided) 95% -0.067 to 0.031 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0252 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 184 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.228 | |
| Confidence Interval |
(2-Sided) 95% 0.161 to 0.296 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0345 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 184 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.265 | |
| Confidence Interval |
(2-Sided) 95% 0.197 to 0.333 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0346 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 184 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.083 | |
| Confidence Interval |
(2-Sided) 95% 0.016 to 0.151 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0343 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.215 | |
| Confidence Interval |
(2-Sided) 95% 0.145 to 0.285 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0358 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.246 | |
| Confidence Interval |
(2-Sided) 95% 0.176 to 0.316 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0357 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.139 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.053 | |
| Confidence Interval |
(2-Sided) 95% -0.017 to 0.122 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0356 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment |
|---|---|
| Description | PEF is a person's maximum speed of expiration. All the participants were instructed to record PEF twice daily using a mini Peak Flow Meter device, once in the morning (before taking the morning dose) and once approximately 12 h later in the evening (before taking the evening dose). At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the e-PEF/diary. The best of 3 values were used. |
| Time Frame | Up to Weeks 26 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study medication. n represents tthe number of participants with data at respective visit. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Week 26: Mean morning PEF |
42.4
(2.15)
|
38.1
(2.15)
|
12.8
(2.13)
|
5.9
(2.14)
|
29.1
(2.14)
|
| Week 26:Mean evening PEF |
32.5
(2.05)
|
30.4
(2.04)
|
7.7
(2.04)
|
0.0
(2.05)
|
23.9
(2.04)
|
| Week 52:Mean morning PEF |
42.1
(2.24)
|
36.9
(2.22)
|
13.4
(2.21)
|
6.7
(2.22)
|
28.3
(2.22)
|
| Week 52:Mean evening PEF |
31.2
(2.14)
|
28.7
(2.13)
|
7.4
(2.13)
|
-0.3
(2.14)
|
22.1
(2.13)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 26: Mean morning PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Linear Mixed Model (LMM) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 29.6 | |
| Confidence Interval |
(2-Sided) 95% 23.8 to 35.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.96 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 26: Mean morning PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 32.2 | |
| Confidence Interval |
(2-Sided) 95% 26.4 to 38.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.97 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 26: Mean morning PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 13.3 | |
| Confidence Interval |
(2-Sided) 95% 7.5 to 19.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.97 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 26: Mean evening PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 24.8 | |
| Confidence Interval |
(2-Sided) 95% 19.3 to 30.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.82 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 26: Mean evening PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 30.4 | |
| Confidence Interval |
(2-Sided) 95% 24.8 to 35.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.83 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 26: Mean evening PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 8.6 | |
| Confidence Interval |
(2-Sided) 95% 3.1 to 14.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.83 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 52: Mean morning PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 28.7 | |
| Confidence Interval |
(2-Sided) 95% 22.7 to 34.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.07 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 52: Mean morning PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 30.2 | |
| Confidence Interval |
(2-Sided) 95% 24.2 to 36.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.07 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 52: Mean morning PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 13.8 | |
| Confidence Interval |
(2-Sided) 95% 7.7 to 19.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.08 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 52: Mean evening PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 23.7 | |
| Confidence Interval |
(2-Sided) 95% 18.0 to 29.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.94 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 52: Mean evening PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 29.1 | |
| Confidence Interval |
(2-Sided) 95% 23.3 to 34.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.94 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 52: Mean evening PEF | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 9.1 | |
| Confidence Interval |
(2-Sided) 95% 3.3 to 14.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.95 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52 |
|---|---|
| Description | Change from baseline in ACQ-7 scores of ≤ 0.5 was defined as minimal clinically important difference and were considered clinically meaningful. The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway calibre (FEV1 % predicted). All 7 questions of the ACQ-7 were equally weighted. Items 1-5 were scored along a 7-point response scale, where 0 = totally controlled and 6 = severely uncontrolled. Item 6 is scored between 0 = no rescue medication and 6 = More than 16 puffs/inhalations most days. The 7th item was scored by the investigator based on the FEV1 % predicted from the masterscope at the site (i.e., Score = 0 means > 95% of predicted FEV1, 1 = 90 - 95%, 2 = 80 - 89%, 3 = 70 - 79%, 4 = 60 - 69%, 5 = 50 - 59%, and Score = 6 means < 50% of predicted FEV1). The total score was calculated as the mean of all questions |
| Time Frame | Weeks 26 (Day 183) and 52 (Day 364) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents number of participants with data at the respective visit. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 442 | 437 | 440 | 443 | 444 |
| Day 183 |
76.4
17.2%
|
76.2
17.4%
|
72.3
16.4%
|
66.9
15.1%
|
75.9
17%
|
| Day 364 |
77.7
17.5%
|
82.1
18.7%
|
73.6
16.7%
|
69.2
15.6%
|
77.3
17.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, QMF149 150/160 μg, MF 800 μg |
|---|---|---|
| Comments | Day 183 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.094 |
| Comments | ||
| Method | Logistic regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.31 | |
| Confidence Interval |
(2-Sided) 95% 0.95 to 1.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 183 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Logistic regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.73 | |
| Confidence Interval |
(2-Sided) 95% 1.26 to 2.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 183 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.746 |
| Comments | ||
| Method | Logistic regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 95% 0.76 to 1.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 364 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.088 |
| Comments | ||
| Method | Logistic regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.34 | |
| Confidence Interval |
(2-Sided) 95% 0.96 to 1.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 364 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Logistic regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.24 | |
| Confidence Interval |
(2-Sided) 95% 1.58 to 3.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 364 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.771 |
| Comments | ||
| Method | Logistic regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.05 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Percentage of Asthma Symptoms Free Days |
|---|---|
| Description | All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. Asthma symptoms free days are days with no daytime symptoms, no night-time awakenings and no symptoms on awakening. The daytime asthma symptom score was based on the daily e-diary recordings by participants with respect to shortness of breath, wheeze, cough, chest tightness, and impact on usual daily activities due to symptoms. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 401 | 402 | 408 | 404 | 405 |
| Least Squares Mean (Standard Error) [percentage of days] |
28.3
(1.72)
|
28.4
(1.72)
|
22.5
(1.72)
|
19.3
(1.72)
|
24.9
(1.72)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | Linear Mixed Model (LMM) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 5.8 | |
| Confidence Interval |
(2-Sided) 95% 1.3 to 10.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.29 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 9.1 | |
| Confidence Interval |
(2-Sided) 95% 4.6 to 13.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.29 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.135 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 3.4 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 7.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.29 |
|
| Estimation Comments | ||
| Title | Change Form Baseline in Percentage of Days With no Daytime Symptoms |
|---|---|
| Description | All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. For days with no daytime symptoms, all 5 evening questions must have a score = 0 with respect to shortness of breath, wheeze, cough, chest tightness and impact on usual daily activities due to symptoms, each with scores from 0 (no problems) to 4 (very severe problems). |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 416 | 420 | 425 | 419 | 423 |
| Least Squares Mean (Standard Error) [percentage of days] |
28.0
(1.69)
|
28.0
(1.69)
|
23.0
(1.68)
|
20.0
(1.69)
|
24.8
(1.68)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 5.0 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 9.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.25 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 8.1 | |
| Confidence Interval |
(2-Sided) 95% 3.7 to 12.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.25 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.151 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 3.2 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 7.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.25 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Percentage of Nights With no Night-time Awakenings |
|---|---|
| Description | All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. The question asked for nights with no night-time awakenings was "How did you sleep last night?" had to be answered with "I did not wake up because of any breathing problems" with scores from 0 (no problem)-4 (very severe problems). |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 415 | 420 | 428 | 422 | 424 |
| Least Squares Mean (Standard Error) [percentage of nights] |
17.0
(1.28)
|
16.4
(1.27)
|
14.2
(1.27)
|
12.5
(1.27)
|
16.1
(1.27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.104 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 2.8 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 6.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.72 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.024 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 3.9 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 7.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.72 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.588 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% -2.5 to 4.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.73 |
|
| Estimation Comments | ||
| Title | Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening |
|---|---|
| Description | All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. The question asked for mornings with no symptoms on awakening was "Did you have asthma symptoms upon awakening in the morning?" to be answered with "None" with scores from 0 (no problem)-4 (very severe problems). |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 415 | 420 | 428 | 422 | 424 |
| Least Squares Mean (Standard Error) [percentage of mornings] |
25.5
(1.66)
|
22.9
(1.65)
|
19.1
(1.65)
|
14.1
(1.65)
|
20.7
(1.65)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 6.4 | |
| Confidence Interval |
(2-Sided) 95% 2.1 to 10.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.19 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 8.9 | |
| Confidence Interval |
(2-Sided) 95% 4.6 to 13.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.19 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.029 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 4.8 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 9.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.2 |
|
| Estimation Comments | ||
| Title | Rescue Medication Usage |
|---|---|
| Description | All participants were given salbutamol/albuterol to use as rescue medication throughout the study along with e-Diary to record rescue medication use. The number of puffs of rescue medication during the past 12 hours is recorded twice (morning/evening) by the participant prior to taking study medication. The mean daily number of puffs of rescue medication use will be calculated for each participant, done separately for morning (night-time), evening (daytime), and daily (night-time plus daytime) rescue medication use |
| Time Frame | Up to Weeks 26 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents number of participants included in the analysis. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Week1-26 Mean night-time number of puffs |
-0.38
(0.028)
|
-0.27
(0.028)
|
-0.26
(0.028)
|
-0.19
(0.028)
|
-0.34
(0.028)
|
| Week1-26 Mean daytime number of puffs |
-0.57
(0.035)
|
-0.46
(0.035)
|
-0.38
(0.035)
|
-0.34
(0.035)
|
-0.53
(0.035)
|
| Week1-26 Mean daily number of puffs |
-0.96
(0.059)
|
-0.73
(0.059)
|
-0.65
(0.059)
|
-0.53
(0.059)
|
-0.87
(0.059)
|
| Week1-52 Mean night-time number of puffs |
-0.40
(0.029)
|
-0.30
(0.029)
|
-0.29
(0.028)
|
-0.20
(0.029)
|
-0.35
(0.029)
|
| Week 1-52 Mean daytime number of puffs |
-0.60
(0.035)
|
-0.51
(0.035)
|
-0.43
(0.035)
|
-0.36
(0.035)
|
-0.55
(0.035)
|
| Week 1-52 Mean daily number of puffs |
-1.00
(0.060)
|
-0.80
(0.060)
|
-0.72
(0.060)
|
-0.56
(0.060)
|
-0.91
(0.060)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week1-26 Mean night-time number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to -0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.039 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 1-26 Mean night-time number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.16 to -0.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.039 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 1-26 Mean night-time number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.261 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.12 to 0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.039 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 1-26 Mean daytime number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.28 to -0.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.047 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 1-26 Mean daytime number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.011 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.21 to -0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.047 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 1-26 Mean daytime number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.425 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.13 to 0.06 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 0.047 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 1-26 Mean daily number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to -0.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 1-26 Mean daily number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.35 to -0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 1-26 Mean daily number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.29 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to -0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 1-52 Mean night-time number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to -0.04 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.039 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 1-52 Mean night-time number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.019 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to -0.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.039 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 1-52 Mean night-time number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.226 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.12 to 0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.039 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 1-52 Mean daytime number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to -0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.048 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 1-52 Mean daytime number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to -0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.048 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 1-52 Mean daytime number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.384 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.14 to 0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.048 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Week 1-52 Mean daily number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.44 to -0.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Week 1-52 Mean daily number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.23 | |
| Confidence Interval |
(2-Sided) 95% -0.39 to -0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Week 1-52 Mean daily number of puffs | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.245 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.25 to 0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
| Estimation Comments | ||
| Title | Time to First Asthma Exacerbation by Exacerbation Category |
|---|---|
| Description | The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Moderate or severe asthma exacerbation |
366.0
|
366.0
|
366.0
|
364.0
|
366.0
|
| Severe asthma exacerbation |
367
|
366
|
366
|
366
|
366
|
| All (mild, moderate or severe) asthma exacerbation |
366.0
|
366.0
|
364.5
|
306.0
|
365.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.39 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.45 | |
| Confidence Interval |
(2-Sided) 95% 0.34 to 0.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.209 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.81 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.54 | |
| Confidence Interval |
(2-Sided) 95% 0.36 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.3 to 0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.115 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.71 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 1.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | All asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.65 | |
| Confidence Interval |
(2-Sided) 95% 0.51 to 0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | All asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 0.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | All asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.185 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Hospitalization for Asthma Exacerbation |
|---|---|
| Description | The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Median (Full Range) [days] |
367.0
|
367.0
|
367.0
|
366.0
|
367.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.337 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.51 | |
| Confidence Interval |
(2-Sided) 95% 0.13 to 2.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.063 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.14 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 1.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.599 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.62 | |
| Confidence Interval |
(2-Sided) 95% 0.27 to 9.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Annual Rate of Asthma Exacerbations by Exacerbation Category |
|---|---|
| Description | The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Moderate or severe asthma exacerbation |
0.25
|
0.27
|
0.39
|
0.56
|
0.27
|
| Severe asthma exacerbation |
0.13
|
0.13
|
0.18
|
0.29
|
0.14
|
| All (mild, moderate, severe) asthma exacerbation |
0.49
|
0.48
|
0.74
|
1.05
|
0.52
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, QMF149 150/160 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.65 | |
| Confidence Interval |
(2-Sided) 95% 0.48 to 0.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.47 | |
| Confidence Interval |
(2-Sided) 95% 0.35 to 0.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.669 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.93 | |
| Confidence Interval |
(2-Sided) 95% 0.67 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.108 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.71 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.46 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 0.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.597 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 1.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | All (mild, moderate, severe) asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.67 | |
| Confidence Interval |
(2-Sided) 95% 0.52 to 0.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | All (mild, moderate, severe) asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.46 | |
| Confidence Interval |
(2-Sided) 95% 0.36 to 0.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | All (mild, moderate, severe) asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.681 |
| Comments | ||
| Method | Generalized linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.95 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 1.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration in Days of Asthma Exacerbations by Exacerbation Category |
|---|---|
| Description | The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participant in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Moderate or severe asthma exacerbation |
2.6
(10.60)
|
3.0
(12.53)
|
3.7
(11.40)
|
5.8
(13.98)
|
3.1
(9.68)
|
| Severe asthma exacerbation |
1.3
(6.02)
|
1.7
(8.48)
|
1.7
(6.07)
|
3.2
(9.16)
|
1.9
(7.76)
|
| All(mild, moderate,severe) asthma exacerbation |
5.4
(18.81)
|
5.0
(17.55)
|
6.9
(22.96)
|
10.1
(25.15)
|
5.1
(14.48)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | van Elteren test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | van Elteren test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Moderate or severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.059 |
| Comments | ||
| Method | van Elteren test | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Severe Asthma Exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | Van Elteren Test | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Severe Asthma Exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Van Elteren Test | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Severe asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | ||
| Method | van Elteren test | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | All(mild, moderate, severe) Asthma Exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Van Elteren Test | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | All (mild, moderate, severe) Asthma Exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Van Elteren Test | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | All (mild, moderate, severe) asthma exacerbation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.074 |
| Comments | ||
| Method | van Elteren test | |
| Comments | ||
| Title | Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category |
|---|---|
| Description | The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all patients in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Moderate or severe asthma exacerbation |
14.9
3.3%
|
16.9
3.8%
|
26.1
5.9%
|
32.5
7.3%
|
19.1
4.3%
|
| Severe asthma exacerbation |
8.1
1.8%
|
9.8
2.2%
|
14.5
3.3%
|
20.1
4.5%
|
11.9
2.7%
|
| Moderate asthma exacerbation |
7.7
1.7%
|
8.2
1.9%
|
14.3
3.2%
|
16.5
3.7%
|
9.2
2.1%
|
| Mild asthma exacerbation |
13.3
3%
|
12.1
2.8%
|
17.5
4%
|
19.6
4.4%
|
15.1
3.4%
|
| All (mild, moderate, severe) asthma exacerbation |
25.5
5.7%
|
25.6
5.8%
|
36.1
8.2%
|
44.5
10%
|
30.6
6.9%
|
| Title | Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations |
|---|---|
| Description | The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol /Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Median (Full Range) [days] |
367.0
|
367.0
|
367.0
|
366.0
|
367.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.222 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 2.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.992 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% 0 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.618 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.54 | |
| Confidence Interval |
(2-Sided) 95% 0.05 to 6.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations |
|---|---|
| Description | |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Number [percentage of participants] |
0.2
0%
|
0
0%
|
0.9
0.2%
|
1.6
0.4%
|
0.5
0.1%
|
| Title | Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations |
|---|---|
| Description | The treatment of asthma exacerbations including the initiation of systemic corticosteroids were done according to investigator's or treating physician's medical judgement and in line with national and international recommendations. If systemic corticosteroids were required, a participant could return to the study after successfully completing a taper of approximately 7-10 days. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Mean (Standard Deviation) [milligrams] |
26.0
(136.92)
|
29.9
(124.98)
|
28.0
(95.18)
|
47.8
(139.98)
|
26.9
(114.36)
|
| Title | Change From Baseline in Percentage of Rescue Medication Free Days |
|---|---|
| Description | All participants were given salbutamol/albuterol to use as rescue medication throughout the study along with e-Diary to record rescue medication use. Rescue medication free days is defined as any day where the participant did not use any puffs of rescue medication during daytime and night-time. |
| Time Frame | Up to Weeks 26 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. n represents number of participants with data at respective visit. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol /Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d via Concept1 inhaler in the evening | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d via Concept1 inhaler in the evening | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d via Twisthaler® in the evening | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Weeks 1-26 |
31.5
(1.53)
|
27.4
(1.53)
|
21.4
(1.52)
|
19.1
(1.53)
|
27.4
(1.52)
|
| Weeks 1-52 |
33.1
(1.55)
|
29.4
(1.54)
|
23.5
(1.54)
|
20.8
(1.54)
|
28.8
(1.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Weeks 1-26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 10.1 | |
| Confidence Interval |
(2-Sided) 95% 6.2 to 14.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.02 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Weeks 1-26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 8.3 | |
| Confidence Interval |
(2-Sided) 95% 4.3 to 12.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.02 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Weeks 1-26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.045 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 4.1 | |
| Confidence Interval |
(2-Sided) 95% 0.1 to 8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.02 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Weeks 1-52 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 9.6 | |
| Confidence Interval |
(2-Sided) 95% 5.7 to 13.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.03 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Weeks 1-52 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 8.6 | |
| Confidence Interval |
(2-Sided) 95% 4.7 to 12.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.03 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Weeks 1-52 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.034 |
| Comments | ||
| Method | LMM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 4.3 | |
| Confidence Interval |
(2-Sided) 95% 0.3 to 8.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.04 |
|
| Estimation Comments | ||
| Title | Asthma Quality of Life Questionnaire (AQLQ) |
|---|---|
| Description | AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). It consists of 4 domains: Symptoms = Mean of Items 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 29, 30 (12 items) Activity limitation = Mean of Items 1, 2, 3, 4, 5, 11, 19, 25, 28, 31, 32 (11 items) Emotional function = Mean of Items 7, 13, 15, 21, 27 (5 items) Environmental stimuli = Mean of Items 9, 17, 23, 26 (4 items) Overall Score = Mean of Items 1 to 32 (32 items) |
| Time Frame | Up to Week 52 (Day 364) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 428 | 426 | 431 | 428 | 438 |
| Day 30 |
5.560
(0.0327)
|
5.498
(0.0328)
|
5.413
(0.0326)
|
5.374
(0.0327)
|
5.515
(0.0324)
|
| Day 86 |
5.618
(0.0356)
|
5.629
(0.0357)
|
5.564
(0.0355)
|
5.510
(0.0359)
|
5.592
(0.0352)
|
| Day 183 |
5.724
(0.0372)
|
5.738
(0.0372)
|
5.598
(0.0372)
|
5.581
(0.0376)
|
5.639
(0.0369)
|
| Day 254 |
5.761
(0.0383)
|
5.781
(0.0382)
|
5.689
(0.0383)
|
5.614
(0.0386)
|
5.700
(0.0378)
|
| Day 364 |
5.783
(0.0391)
|
5.832
(0.0388)
|
5.705
(0.0389)
|
5.641
(0.0394)
|
5.742
(0.0384)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 30 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.147 | |
| Confidence Interval |
(2-Sided) 95% 0.056 to 0.237 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0462 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 30 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.123 | |
| Confidence Interval |
(2-Sided) 95% 0.032 to 0.214 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0464 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 30 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.33 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.045 | |
| Confidence Interval |
(2-Sided) 95% -0.045 to 0.135 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.046 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 86 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.28 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.054 | |
| Confidence Interval |
(2-Sided) 95% -0.044 to 0.153 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0503 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 86 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.02 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.118 | |
| Confidence Interval |
(2-Sided) 95% 0.019 to 0.217 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0507 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 86 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.598 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.026 | |
| Confidence Interval |
(2-Sided) 95% -0.072 to 0.125 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0501 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 183 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.016 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.127 | |
| Confidence Interval |
(2-Sided) 95% 0.023 to 0.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0526 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 183 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.156 | |
| Confidence Interval |
(2-Sided) 95% 0.053 to 0.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0529 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 183 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.103 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.085 | |
| Confidence Interval |
(2-Sided) 95% -0.017 to 0.188 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0525 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 254 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.188 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.071 | |
| Confidence Interval |
(2-Sided) 95% -0.035 to 0.178 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0542 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 254 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.168 | |
| Confidence Interval |
(2-Sided) 95% 0.061 to 0.274 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0543 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 254 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.258 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.061 | |
| Confidence Interval |
(2-Sided) 95% -0.045 to 0.166 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0538 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, MF 800 μg |
|---|---|---|
| Comments | Day 364 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.154 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.079 | |
| Confidence Interval |
(2-Sided) 95% -0.030 to 0.187 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0552 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/160 μg, MF 400 μg |
|---|---|---|
| Comments | Day 364 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.191 | |
| Confidence Interval |
(2-Sided) 95% 0.082 to 0.299 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0553 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | Day 364 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.455 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.041 | |
| Confidence Interval |
(2-Sided) 95% -0.067 to 0.148 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0548 |
|
| Estimation Comments | ||
| Title | Trough FEV1 Measured After 26 Weeks of Treatment |
|---|---|
| Description | Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS consisted of all participants in the RAN set who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 395 | 389 | 372 | 376 | 391 |
| Least Squares Mean (Standard Error) [L] |
2.383
(0.0159)
|
2.387
(0.0160)
|
2.250
(0.0162)
|
2.176
(0.0162)
|
2.346
(0.0160)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QMF149 150/320 μg, Salmeterol/Fluticasone 50/500 μg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | QMF 150/320 was considered non-inferior to S/F 50/500 if the lower bound of the 95% CI was above the non-inferiority margin of -90 mL and was considered superior if the lower bound of the 95% CI was > 0. The p-value is for null-hypothesis testing. | |
| Statistical Test of Hypothesis | p-Value | 0.101 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 0.036 | |
| Confidence Interval |
(2-Sided) 95% -0.007 to 0.080 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0222 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes |
|---|---|
| Description | A composite endpoint of serious asthma outcomes is defined as asthma-related hospitalization, asthma-related intubation, or asthma-related death and was reviewed by the Adjudication Committee. |
| Time Frame | Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Set consisted of all participants who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Number [percentage of participants] |
0.7
0.2%
|
0.5
0.1%
|
1.6
0.4%
|
1.8
0.4%
|
0.5
0.1%
|
| Title | Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
|---|---|
| Description | An AE is any untoward medical occurrence (i.e., any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s) or medical conditions(s) which meets any one of the following criteria: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant, i.e. defined as an event that jeopardizes the participants or may require medical or surgical intervention. |
| Time Frame | Approximately up to 56 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Set consisted of all participants who received at least one dose of study medication. |
| Arm/Group Title | QMF149 150/320 μg | QMF149 150/160 μg | MF 800 μg | MF 400 μg | Salmeterol/Fluticasone 50/500 μg |
|---|---|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. |
| Measure Participants | 443 | 437 | 440 | 443 | 444 |
| Adverse Events(AEs) |
64.6
14.5%
|
66.8
15.2%
|
70.0
15.8%
|
72.2
16.3%
|
65.3
14.6%
|
| Serious Adverse Events(SAEs) |
4.7
1.1%
|
4.6
1%
|
4.8
1.1%
|
7.0
1.6%
|
4.7
1.1%
|
Adverse Events
| Time Frame | Serious adverse events: From first dose up to 30 days post last dose (approximately 56 weeks) Other adverse events: From first dose up to 7 days post last dose (approximately 53 weeks) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety Set consisted of all participants who received at least one dose of study medication. | |||||||||
| Arm/Group Title | QMF 150/320 | QMF 150/160 | MF 800 | MF 400 | S/F 50/500 | |||||
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening. | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening. | MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®. | MF 400 μg was delivered o.d. via Twisthaler® in the evening. | Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®. | |||||
All Cause Mortality |
||||||||||
| QMF 150/320 | QMF 150/160 | MF 800 | MF 400 | S/F 50/500 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
Serious Adverse Events |
||||||||||
| QMF 150/320 | QMF 150/160 | MF 800 | MF 400 | S/F 50/500 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/443 (4.7%) | 20/437 (4.6%) | 21/440 (4.8%) | 31/443 (7%) | 21/444 (4.7%) | |||||
| Cardiac disorders | ||||||||||
| Acute myocardial infarction | 2/443 (0.5%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Atrial fibrillation | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Coronary artery disease | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Vertigo | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Endocrine disorders | ||||||||||
| Goitre | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Eye disorders | ||||||||||
| Corneal deposits | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Optic ischaemic neuropathy | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Retinal detachment | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal hernia | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Abdominal pain upper | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Diverticulum intestinal | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Diverticulum intestinal haemorrhagic | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Gastric polyps | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Gastric ulcer haemorrhage | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Gastritis | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Inguinal hernia | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Irritable bowel syndrome | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Large intestine polyp | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Pancreatitis acute | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Peptic ulcer | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholecystitis acute | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Cholelithiasis | 1/443 (0.2%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Infections and infestations | ||||||||||
| Appendicitis | 1/443 (0.2%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Complicated appendicitis | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Dengue fever | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Diverticulitis | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Gastroenteritis salmonella | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Lower respiratory tract infection | 0/443 (0%) | 1/437 (0.2%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Otitis media | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Peritonitis | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 3/444 (0.7%) | |||||
| Pneumonia | 1/443 (0.2%) | 3/437 (0.7%) | 5/440 (1.1%) | 2/443 (0.5%) | 0/444 (0%) | |||||
| Pneumonia viral | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Pulmonary tuberculosis | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Respiratory tract infection bacterial | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Sepsis | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Sialoadenitis | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Upper respiratory tract infection bacterial | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Urinary tract infection | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Accidental device ingestion | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Ankle fracture | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Clavicle fracture | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Concussion | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Eye injury | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Forearm fracture | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Hand fracture | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Head injury | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Humerus fracture | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Ligament sprain | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Meniscus injury | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Postoperative wound complication | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Radius fracture | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Rib fracture | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 2/443 (0.5%) | 0/444 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Aspartate aminotransferase increased | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Blood bilirubin increased | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Diabetes mellitus inadequate control | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Electrolyte imbalance | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Type 2 diabetes mellitus | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthropathy | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Back pain | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Bursitis | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Foot deformity | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Intervertebral disc protrusion | 1/443 (0.2%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Joint effusion | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Osteochondrosis | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Osteoporosis | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Rotator cuff syndrome | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Neoplasm | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Papillary thyroid cancer | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Renal neoplasm | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Uterine cancer | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Uterine leiomyoma | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 1/444 (0.2%) | |||||
| Nervous system disorders | ||||||||||
| Cerebellar haematoma | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Cerebral infarction | 1/443 (0.2%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Headache | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Hydrocephalus | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Intracranial aneurysm | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Migraine with aura | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Sciatica | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Subarachnoid haemorrhage | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Vertebral artery aneurysm | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Psychiatric disorders | ||||||||||
| Depression | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Renal and urinary disorders | ||||||||||
| Calculus urethral | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Hydronephrosis | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Hydroureter | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Ureteric stenosis | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Ureterolithiasis | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Urethral stenosis | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Benign prostatic hyperplasia | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Cervical dysplasia | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Cervix enlargement | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Endometrial hyperplasia | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Endometriosis | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Metrorrhagia | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Vaginal prolapse | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Asphyxia | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Asthma | 3/443 (0.7%) | 2/437 (0.5%) | 6/440 (1.4%) | 8/443 (1.8%) | 2/444 (0.5%) | |||||
| Atelectasis | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Chronic rhinosinusitis with nasal polyps | 0/443 (0%) | 1/437 (0.2%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Haemothorax | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Hydrothorax | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Nasal polyps | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 0/443 (0%) | 1/444 (0.2%) | |||||
| Nasal septum deviation | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Pleurisy | 0/443 (0%) | 0/437 (0%) | 1/440 (0.2%) | 0/443 (0%) | 0/444 (0%) | |||||
| Pulmonary mass | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Angioedema | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Dermatitis atopic | 0/443 (0%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
| Vascular disorders | ||||||||||
| Aortic dissection | 0/443 (0%) | 1/437 (0.2%) | 0/440 (0%) | 0/443 (0%) | 0/444 (0%) | |||||
| Hypertensive crisis | 1/443 (0.2%) | 0/437 (0%) | 0/440 (0%) | 1/443 (0.2%) | 0/444 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| QMF 150/320 | QMF 150/160 | MF 800 | MF 400 | S/F 50/500 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 228/443 (51.5%) | 233/437 (53.3%) | 263/440 (59.8%) | 290/443 (65.5%) | 239/444 (53.8%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 3/443 (0.7%) | 9/437 (2.1%) | 5/440 (1.1%) | 4/443 (0.9%) | 9/444 (2%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 20/443 (4.5%) | 22/437 (5%) | 22/440 (5%) | 21/443 (4.7%) | 17/444 (3.8%) | |||||
| Gastroenteritis | 4/443 (0.9%) | 9/437 (2.1%) | 4/440 (0.9%) | 6/443 (1.4%) | 8/444 (1.8%) | |||||
| Influenza | 12/443 (2.7%) | 13/437 (3%) | 19/440 (4.3%) | 10/443 (2.3%) | 15/444 (3.4%) | |||||
| Nasopharyngitis | 50/443 (11.3%) | 58/437 (13.3%) | 78/440 (17.7%) | 82/443 (18.5%) | 47/444 (10.6%) | |||||
| Pharyngitis | 10/443 (2.3%) | 11/437 (2.5%) | 12/440 (2.7%) | 12/443 (2.7%) | 14/444 (3.2%) | |||||
| Respiratory tract infection viral | 10/443 (2.3%) | 16/437 (3.7%) | 14/440 (3.2%) | 12/443 (2.7%) | 13/444 (2.9%) | |||||
| Rhinitis | 10/443 (2.3%) | 10/437 (2.3%) | 9/440 (2%) | 5/443 (1.1%) | 8/444 (1.8%) | |||||
| Upper respiratory tract infection | 22/443 (5%) | 27/437 (6.2%) | 40/440 (9.1%) | 37/443 (8.4%) | 38/444 (8.6%) | |||||
| Upper respiratory tract infection bacterial | 5/443 (1.1%) | 7/437 (1.6%) | 6/440 (1.4%) | 14/443 (3.2%) | 8/444 (1.8%) | |||||
| Viral infection | 7/443 (1.6%) | 8/437 (1.8%) | 11/440 (2.5%) | 7/443 (1.6%) | 6/444 (1.4%) | |||||
| Viral upper respiratory tract infection | 7/443 (1.6%) | 11/437 (2.5%) | 21/440 (4.8%) | 20/443 (4.5%) | 21/444 (4.7%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 9/443 (2%) | 17/437 (3.9%) | 9/440 (2%) | 5/443 (1.1%) | 8/444 (1.8%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 26/443 (5.9%) | 21/437 (4.8%) | 24/440 (5.5%) | 23/443 (5.2%) | 22/444 (5%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Asthma | 112/443 (25.3%) | 113/437 (25.9%) | 157/440 (35.7%) | 194/443 (43.8%) | 137/444 (30.9%) | |||||
| Cough | 8/443 (1.8%) | 9/437 (2.1%) | 12/440 (2.7%) | 15/443 (3.4%) | 8/444 (1.8%) | |||||
| Oropharyngeal pain | 11/443 (2.5%) | 6/437 (1.4%) | 8/440 (1.8%) | 9/443 (2%) | 8/444 (1.8%) | |||||
| Rhinitis allergic | 5/443 (1.1%) | 11/437 (2.5%) | 7/440 (1.6%) | 11/443 (2.5%) | 7/444 (1.6%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 10/443 (2.3%) | 14/437 (3.2%) | 13/440 (3%) | 11/443 (2.5%) | 6/444 (1.4%) | |||||
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 or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02554786
Other Study ID Numbers:
- CQVM149B2301
- 2015-002529-21
First Posted:
Sep 18, 2015
Last Update Posted:
Mar 5, 2020
Last Verified:
Feb 1, 2020