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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02554786

Enrollment

2216

Registered

2015-09-18

Start date

2015-12-29

Completion date

2019-06-28

Last updated

2020-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

QMF149, Mometasone furoate (MF), asthma

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

Interventions

DRUGIndacaterol acetate/Mometasone furoate

DRUGMometasone furoate

DRUGSalmeterol xinafoate/fluticasone propionate

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

12 Years to 75 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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.
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.
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.

Countries

Bulgaria, China, Croatia, Czechia, Egypt, Estonia, Germany, Guatemala, Hungary, India, Ireland, Japan, Latvia, Lithuania, Mexico, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, United Kingdom, United States

Participant flow

Recruitment details

Participants took part in 316 investigative sites in 24 countries from 29 Dec 2015 to 28 Jun 2019.

Pre-assignment details

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.

Participants by arm

Arm	Count
QMF149 150/320 μg QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d. via Concept1 inhaler in the evening.	445
QMF149 150/160 μg QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered o.d. via Concept1 inhaler in the evening.	439
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®.	442
MF 400 μg MF 400 μg was delivered o.d. via Twisthaler® in the evening.	444
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®.	446
Total	2,216

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	0	0	0	0	2
Overall Study	Death	0	0	0	1	0
Overall Study	Lost to Follow-up	4	3	4	2	2
Overall Study	Non-compliance with study treatment	0	1	1	0	1
Overall Study	Physician Decision	0	1	4	1	1
Overall Study	Pregnancy	0	0	0	1	1
Overall Study	Protocol deviation	1	3	3	4	2
Overall Study	Subject/guardian decision	29	17	18	30	20
Overall Study	Technical problems	1	1	0	2	1

Baseline characteristics

Characteristic	QMF149 150/320 μg	QMF149 150/160 μg	MF 400 μg	Salmeterol/Fluticasone 50/500 μg	MF 800 μg	Total
Age, Continuous	47.1 years STANDARD_DEVIATION 14.56	47.4 years STANDARD_DEVIATION 14.76	48.7 years STANDARD_DEVIATION 14.98	48.9 years STANDARD_DEVIATION 14.59	47.5 years STANDARD_DEVIATION 14.99	47.9 years STANDARD_DEVIATION 14.78
Race/Ethnicity, Customized Ethnicity East Asian	52 Participants	48 Participants	55 Participants	53 Participants	51 Participants	259 Participants
Race/Ethnicity, Customized Ethnicity Hispanic Or Latino	21 Participants	17 Participants	22 Participants	15 Participants	14 Participants	89 Participants
Race/Ethnicity, Customized Ethnicity Mixed ethnicity	10 Participants	10 Participants	5 Participants	15 Participants	9 Participants	49 Participants
Race/Ethnicity, Customized Ethnicity Not reported	12 Participants	4 Participants	5 Participants	9 Participants	12 Participants	42 Participants
Race/Ethnicity, Customized Ethnicity Other	218 Participants	225 Participants	239 Participants	227 Participants	242 Participants	1151 Participants
Race/Ethnicity, Customized Ethnicity Russian	79 Participants	79 Participants	62 Participants	65 Participants	64 Participants	349 Participants
Race/Ethnicity, Customized Ethnicity South Asian	3 Participants	3 Participants	3 Participants	3 Participants	2 Participants	14 Participants
Race/Ethnicity, Customized Ethnicity Southeast Asian	38 Participants	40 Participants	38 Participants	42 Participants	42 Participants	200 Participants
Race/Ethnicity, Customized Ethnicity Unknown	12 Participants	13 Participants	15 Participants	17 Participants	6 Participants	63 Participants
Race/Ethnicity, Customized Race Asian	97 Participants	98 Participants	98 Participants	102 Participants	98 Participants	493 Participants
Race/Ethnicity, Customized Race Black	5 Participants	2 Participants	8 Participants	4 Participants	4 Participants	23 Participants
Race/Ethnicity, Customized Race Caucasian	313 Participants	311 Participants	312 Participants	305 Participants	318 Participants	1559 Participants
Race/Ethnicity, Customized Race Native American	13 Participants	14 Participants	18 Participants	12 Participants	11 Participants	68 Participants
Race/Ethnicity, Customized Race Other	16 Participants	14 Participants	8 Participants	23 Participants	11 Participants	72 Participants
Race/Ethnicity, Customized Race Pacific Islander	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Sex: Female, Male Female	262 Participants	253 Participants	272 Participants	256 Participants	250 Participants	1293 Participants
Sex: Female, Male Male	183 Participants	186 Participants	172 Participants	190 Participants	192 Participants	923 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 443	0 / 437	0 / 440	1 / 443	0 / 444
other Total, other adverse events	228 / 443	233 / 437	263 / 440	290 / 443	239 / 444
serious Total, serious adverse events	21 / 443	20 / 437	21 / 440	31 / 443	21 / 444

Outcome results

Primary

Trough Forced Expiratory Volume in One Second (Trough FEV1) at 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.

Time frame: 26 weeks

Population: Full Analysis Set (FAS) consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26	2.383 litre (L)	Standard Error 0.0159
QMF149 150/160 μg	Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26	2.387 litre (L)	Standard Error 0.016
MF 800 μg	Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26	2.250 litre (L)	Standard Error 0.0162
MF 400 μg	Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26	2.176 litre (L)	Standard Error 0.0162
Salmeterol/Fluticasone 50/500 μg	Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26	2.346 litre (L)	Standard Error 0.016

p-value: <0.00195% CI: [0.088, 0.176]Mixed Model for Repeated Measures (MMRM)

p-value: <0.00195% CI: [0.167, 0.255]MMRM

Secondary

Annual Rate of Asthma Exacerbations by Exacerbation Category

The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.

Time frame: Up to Week 52

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Group	Value (MEAN)
QMF149 150/320 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	0.25 exacerbations per year
QMF149 150/320 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	0.49 exacerbations per year
QMF149 150/320 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	0.13 exacerbations per year
QMF149 150/160 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	0.13 exacerbations per year
QMF149 150/160 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	0.27 exacerbations per year
QMF149 150/160 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	0.48 exacerbations per year
MF 800 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	0.18 exacerbations per year
MF 800 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	0.39 exacerbations per year
MF 800 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	0.74 exacerbations per year
MF 400 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	0.56 exacerbations per year
MF 400 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	1.05 exacerbations per year
MF 400 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	0.29 exacerbations per year
Salmeterol/Fluticasone 50/500 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	0.14 exacerbations per year
Salmeterol/Fluticasone 50/500 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	0.27 exacerbations per year
Salmeterol/Fluticasone 50/500 μg	Annual Rate of Asthma Exacerbations by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	0.52 exacerbations per year

Comparison: Moderate or severe asthma exacerbationp-value: 0.00895% CI: [0.48, 0.89]Generalized linear model

Comparison: Moderate or severe asthma exacerbationp-value: <0.00195% CI: [0.35, 0.64]Generalized linear model

Comparison: Moderate or severe asthma exacerbationp-value: 0.66995% CI: [0.67, 1.29]Generalized linear model

Comparison: Severe asthma exacerbationp-value: 0.10895% CI: [0.47, 1.08]Generalized linear model

Comparison: Severe asthma exacerbationp-value: <0.00195% CI: [0.31, 0.67]Generalized linear model

Comparison: Severe asthma exacerbationp-value: 0.59795% CI: [0.58, 1.37]Generalized linear model

Comparison: All (mild, moderate, severe) asthma exacerbationp-value: 0.00295% CI: [0.52, 0.87]Generalized linear model

Comparison: All (mild, moderate, severe) asthma exacerbationp-value: <0.00195% CI: [0.36, 0.59]Generalized linear model

Comparison: All (mild, moderate, severe) asthma exacerbationp-value: 0.68195% CI: [0.72, 1.23]Generalized linear model

Secondary

Asthma Control Questionnaire (ACQ-7) at 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.

Time frame: Weeks 4, 12, 26 and 52

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 4	1.486 score on a scale	Standard Error 0.0337
QMF149 150/320 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 12	1.394 score on a scale	Standard Error 0.0347
QMF149 150/320 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 26	1.267 score on a scale	Standard Error 0.035
QMF149 150/320 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 52	1.231 score on a scale	Standard Error 0.0358
QMF149 150/160 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 4	1.533 score on a scale	Standard Error 0.0338
QMF149 150/160 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 52	1.183 score on a scale	Standard Error 0.0356
QMF149 150/160 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 12	1.377 score on a scale	Standard Error 0.0348
QMF149 150/160 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 26	1.261 score on a scale	Standard Error 0.035
MF 800 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 52	1.373 score on a scale	Standard Error 0.0359
MF 800 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 12	1.523 score on a scale	Standard Error 0.0348
MF 800 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 26	1.439 score on a scale	Standard Error 0.0352
MF 800 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 4	1.659 score on a scale	Standard Error 0.0338
MF 400 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 4	1.730 score on a scale	Standard Error 0.0337
MF 400 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 12	1.625 score on a scale	Standard Error 0.035
MF 400 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 52	1.449 score on a scale	Standard Error 0.0361
MF 400 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 26	1.509 score on a scale	Standard Error 0.0354
Salmeterol/Fluticasone 50/500 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 52	1.221 score on a scale	Standard Error 0.0354
Salmeterol/Fluticasone 50/500 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 26	1.322 score on a scale	Standard Error 0.0349
Salmeterol/Fluticasone 50/500 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 12	1.445 score on a scale	Standard Error 0.0345
Salmeterol/Fluticasone 50/500 μg	Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52	Week 4	1.541 score on a scale	Standard Error 0.0335

Comparison: Week 52p-value: <0.00195% CI: [-0.354, -0.177]MMRM

Comparison: Week 52p-value: 0.82495% CI: [-0.078, 0.098]MMRM

Comparison: 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.p-value: <0.00195% CI: [-0.266, -0.141]MMRM

Comparison: Week 4p-value: <0.00195% CI: [-0.254, -0.091]MMRM

Comparison: Week 4p-value: <0.00195% CI: [-0.278, -0.115]MMRM

Comparison: Week 4p-value: 0.18695% CI: [-0.136, 0.026]MMRM

Comparison: 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.p-value: <0.00195% CI: [-0.242, -0.127]MMRM

Comparison: Week 12p-value: 0.00395% CI: [-0.214, -0.044]MMRM

Comparison: Week 12p-value: <0.00195% CI: [-0.333, -0.162]MMRM

Comparison: Week 12p-value: 0.23295% CI: [-0.136, 0.033]MMRM

Comparison: 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.p-value: <0.00195% CI: [-0.248, -0.128]MMRM

Comparison: Week 26p-value: <0.00195% CI: [-0.257, -0.086]MMRM

Comparison: Week 26p-value: <0.00195% CI: [-0.334, -0.162]MMRM

Comparison: Week 26p-value: 0.21495% CI: [-0.14, 0.031]MMRM

Comparison: 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.p-value: <0.00195% CI: [-0.27, -0.149]MMRM

Comparison: Week 52p-value: 0.00295% CI: [-0.229, -0.053]MMRM

Secondary

Asthma Quality of Life Questionnaire (AQLQ)

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)

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 254	5.761 score on a scale	Standard Error 0.0383
QMF149 150/320 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 30	5.560 score on a scale	Standard Error 0.0327
QMF149 150/320 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 364	5.783 score on a scale	Standard Error 0.0391
QMF149 150/320 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 86	5.618 score on a scale	Standard Error 0.0356
QMF149 150/320 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 183	5.724 score on a scale	Standard Error 0.0372
QMF149 150/160 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 254	5.781 score on a scale	Standard Error 0.0382
QMF149 150/160 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 183	5.738 score on a scale	Standard Error 0.0372
QMF149 150/160 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 86	5.629 score on a scale	Standard Error 0.0357
QMF149 150/160 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 364	5.832 score on a scale	Standard Error 0.0388
QMF149 150/160 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 30	5.498 score on a scale	Standard Error 0.0328
MF 800 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 183	5.598 score on a scale	Standard Error 0.0372
MF 800 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 30	5.413 score on a scale	Standard Error 0.0326
MF 800 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 86	5.564 score on a scale	Standard Error 0.0355
MF 800 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 254	5.689 score on a scale	Standard Error 0.0383
MF 800 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 364	5.705 score on a scale	Standard Error 0.0389
MF 400 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 364	5.641 score on a scale	Standard Error 0.0394
MF 400 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 30	5.374 score on a scale	Standard Error 0.0327
MF 400 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 254	5.614 score on a scale	Standard Error 0.0386
MF 400 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 183	5.581 score on a scale	Standard Error 0.0376
MF 400 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 86	5.510 score on a scale	Standard Error 0.0359
Salmeterol/Fluticasone 50/500 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 183	5.639 score on a scale	Standard Error 0.0369
Salmeterol/Fluticasone 50/500 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 254	5.700 score on a scale	Standard Error 0.0378
Salmeterol/Fluticasone 50/500 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 30	5.515 score on a scale	Standard Error 0.0324
Salmeterol/Fluticasone 50/500 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 364	5.742 score on a scale	Standard Error 0.0384
Salmeterol/Fluticasone 50/500 μg	Asthma Quality of Life Questionnaire (AQLQ)	Day 86	5.592 score on a scale	Standard Error 0.0352

Comparison: Day 30p-value: 0.00295% CI: [0.056, 0.237]MMRM

Comparison: Day 30p-value: 0.00895% CI: [0.032, 0.214]MMRM

Comparison: Day 30p-value: 0.3395% CI: [-0.045, 0.135]MMRM

Comparison: Day 86p-value: 0.2895% CI: [-0.044, 0.153]MMRM

Comparison: Day 86p-value: 0.0295% CI: [0.019, 0.217]MMRM

Comparison: Day 86p-value: 0.59895% CI: [-0.072, 0.125]MMRM

Comparison: Day 183p-value: 0.01695% CI: [0.023, 0.23]MMRM

Comparison: Day 183p-value: 0.00395% CI: [0.053, 0.26]MMRM

Comparison: Day 183p-value: 0.10395% CI: [-0.017, 0.188]MMRM

Comparison: Day 254p-value: 0.18895% CI: [-0.035, 0.178]MMRM

Comparison: Day 254p-value: 0.00295% CI: [0.061, 0.274]MMRM

Comparison: Day 254p-value: 0.25895% CI: [-0.045, 0.166]MMRM

Comparison: Day 364p-value: 0.15495% CI: [-0.03, 0.187]MMRM

Comparison: Day 364p-value: <0.00195% CI: [0.082, 0.299]MMRM

Comparison: Day 364p-value: 0.45595% CI: [-0.067, 0.148]MMRM

Secondary

Change Form Baseline in Percentage of Days With no Daytime Symptoms

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

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Change Form Baseline in Percentage of Days With no Daytime Symptoms	28.0 percentage of days	Standard Error 1.69
QMF149 150/160 μg	Change Form Baseline in Percentage of Days With no Daytime Symptoms	28.0 percentage of days	Standard Error 1.69
MF 800 μg	Change Form Baseline in Percentage of Days With no Daytime Symptoms	23.0 percentage of days	Standard Error 1.68
MF 400 μg	Change Form Baseline in Percentage of Days With no Daytime Symptoms	20.0 percentage of days	Standard Error 1.69
Salmeterol/Fluticasone 50/500 μg	Change Form Baseline in Percentage of Days With no Daytime Symptoms	24.8 percentage of days	Standard Error 1.68

p-value: 0.02695% CI: [0.6, 9.4]LMM

p-value: <0.00195% CI: [3.7, 12.5]LMM

p-value: 0.15195% CI: [-1.2, 7.7]LMM

Secondary

Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening

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

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening	25.5 percentage of mornings	Standard Error 1.66
QMF149 150/160 μg	Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening	22.9 percentage of mornings	Standard Error 1.65
MF 800 μg	Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening	19.1 percentage of mornings	Standard Error 1.65
MF 400 μg	Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening	14.1 percentage of mornings	Standard Error 1.65
Salmeterol/Fluticasone 50/500 μg	Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening	20.7 percentage of mornings	Standard Error 1.65

p-value: 0.00395% CI: [2.1, 10.7]LMM

p-value: <0.00195% CI: [4.6, 13.2]LMM

p-value: 0.02995% CI: [0.5, 9.1]LMM

Secondary

Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26: Mean morning PEF	42.4 L/min	Standard Error 2.15
QMF149 150/320 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26:Mean evening PEF	32.5 L/min	Standard Error 2.05
QMF149 150/320 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean morning PEF	42.1 L/min	Standard Error 2.24
QMF149 150/320 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean evening PEF	31.2 L/min	Standard Error 2.14
QMF149 150/160 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26: Mean morning PEF	38.1 L/min	Standard Error 2.15
QMF149 150/160 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean evening PEF	28.7 L/min	Standard Error 2.13
QMF149 150/160 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26:Mean evening PEF	30.4 L/min	Standard Error 2.04
QMF149 150/160 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean morning PEF	36.9 L/min	Standard Error 2.22
MF 800 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean evening PEF	7.4 L/min	Standard Error 2.13
MF 800 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26:Mean evening PEF	7.7 L/min	Standard Error 2.04
MF 800 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean morning PEF	13.4 L/min	Standard Error 2.21
MF 800 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26: Mean morning PEF	12.8 L/min	Standard Error 2.13
MF 400 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26: Mean morning PEF	5.9 L/min	Standard Error 2.14
MF 400 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26:Mean evening PEF	0.0 L/min	Standard Error 2.05
MF 400 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean evening PEF	-0.3 L/min	Standard Error 2.14
MF 400 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean morning PEF	6.7 L/min	Standard Error 2.22
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean evening PEF	22.1 L/min	Standard Error 2.13
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 52:Mean morning PEF	28.3 L/min	Standard Error 2.22
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26:Mean evening PEF	23.9 L/min	Standard Error 2.04
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	Week 26: Mean morning PEF	29.1 L/min	Standard Error 2.14

Comparison: Week 26: Mean morning PEFp-value: <0.00195% CI: [23.8, 35.4]Linear Mixed Model (LMM)

Comparison: Week 26: Mean morning PEFp-value: <0.00195% CI: [26.4, 38.1]LMM

Comparison: Week 26: Mean morning PEFp-value: <0.00195% CI: [7.5, 19.1]LMM

Comparison: Week 26: Mean evening PEFp-value: <0.00195% CI: [19.3, 30.3]LMM

Comparison: Week 26: Mean evening PEFp-value: <0.00195% CI: [24.8, 35.9]LMM

Comparison: Week 26: Mean evening PEFp-value: 0.00295% CI: [3.1, 14.2]LMM

Comparison: Week 52: Mean morning PEFp-value: <0.00195% CI: [22.7, 34.8]LMM

Comparison: Week 52: Mean morning PEFp-value: <0.00195% CI: [24.2, 36.3]LMM

Comparison: Week 52: Mean morning PEFp-value: <0.00195% CI: [7.7, 19.8]LMM

Comparison: Week 52: Mean evening PEFp-value: <0.00195% CI: [18, 29.5]LMM

Comparison: Week 52: Mean evening PEFp-value: <0.00195% CI: [23.3, 34.8]LMM

Comparison: Week 52: Mean evening PEFp-value: 0.00295% CI: [3.3, 14.9]LMM

Secondary

Change From Baseline in Percentage of Asthma Symptoms Free Days

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

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Change From Baseline in Percentage of Asthma Symptoms Free Days	28.3 percentage of days	Standard Error 1.72
QMF149 150/160 μg	Change From Baseline in Percentage of Asthma Symptoms Free Days	28.4 percentage of days	Standard Error 1.72
MF 800 μg	Change From Baseline in Percentage of Asthma Symptoms Free Days	22.5 percentage of days	Standard Error 1.72
MF 400 μg	Change From Baseline in Percentage of Asthma Symptoms Free Days	19.3 percentage of days	Standard Error 1.72
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Percentage of Asthma Symptoms Free Days	24.9 percentage of days	Standard Error 1.72

p-value: 0.01295% CI: [1.3, 10.2]Linear Mixed Model (LMM)

p-value: <0.00195% CI: [4.6, 13.6]LMM

p-value: 0.13595% CI: [-1.1, 7.9]LMM

Secondary

Change From Baseline in Percentage of Nights With no Night-time Awakenings

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

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Change From Baseline in Percentage of Nights With no Night-time Awakenings	17.0 percentage of nights	Standard Error 1.28
QMF149 150/160 μg	Change From Baseline in Percentage of Nights With no Night-time Awakenings	16.4 percentage of nights	Standard Error 1.27
MF 800 μg	Change From Baseline in Percentage of Nights With no Night-time Awakenings	14.2 percentage of nights	Standard Error 1.27
MF 400 μg	Change From Baseline in Percentage of Nights With no Night-time Awakenings	12.5 percentage of nights	Standard Error 1.27
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Percentage of Nights With no Night-time Awakenings	16.1 percentage of nights	Standard Error 1.27

p-value: 0.10495% CI: [-0.6, 6.2]LMM

p-value: 0.02495% CI: [0.5, 7.3]LMM

p-value: 0.58895% CI: [-2.5, 4.3]LMM

Secondary

Change From Baseline in Percentage of Rescue Medication Free Days

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-26	31.5 percentage of days	Standard Error 1.53
QMF149 150/320 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-52	33.1 percentage of days	Standard Error 1.55
QMF149 150/160 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-26	27.4 percentage of days	Standard Error 1.53
QMF149 150/160 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-52	29.4 percentage of days	Standard Error 1.54
MF 800 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-26	21.4 percentage of days	Standard Error 1.52
MF 800 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-52	23.5 percentage of days	Standard Error 1.54
MF 400 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-52	20.8 percentage of days	Standard Error 1.54
MF 400 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-26	19.1 percentage of days	Standard Error 1.53
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-26	27.4 percentage of days	Standard Error 1.52
Salmeterol/Fluticasone 50/500 μg	Change From Baseline in Percentage of Rescue Medication Free Days	Weeks 1-52	28.8 percentage of days	Standard Error 1.54

Comparison: Weeks 1-26p-value: <0.00195% CI: [6.2, 14.1]LMM

Comparison: Weeks 1-26p-value: <0.00195% CI: [4.3, 12.3]LMM

Comparison: Weeks 1-26p-value: 0.04595% CI: [0.1, 8]LMM

Comparison: Weeks 1-52p-value: <0.00195% CI: [5.7, 13.6]LMM

Comparison: Weeks 1-52p-value: <0.00195% CI: [4.7, 12.6]LMM

Comparison: Weeks 1-52p-value: 0.03495% CI: [0.3, 8.3]LMM

Secondary

Duration in Days of Asthma Exacerbations by Exacerbation Category

The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.

Time frame: Up to Week 52

Population: FAS consisted of all participant in the RAN set who received at least one dose of study medication.

Arm	Measure	Group	Value (MEAN)	Dispersion
QMF149 150/320 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	2.6 days	Standard Deviation 10.6
QMF149 150/320 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	All(mild, moderate,severe) asthma exacerbation	5.4 days	Standard Deviation 18.81
QMF149 150/320 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	1.3 days	Standard Deviation 6.02
QMF149 150/160 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	1.7 days	Standard Deviation 8.48
QMF149 150/160 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	3.0 days	Standard Deviation 12.53
QMF149 150/160 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	All(mild, moderate,severe) asthma exacerbation	5.0 days	Standard Deviation 17.55
MF 800 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	1.7 days	Standard Deviation 6.07
MF 800 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	3.7 days	Standard Deviation 11.4
MF 800 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	All(mild, moderate,severe) asthma exacerbation	6.9 days	Standard Deviation 22.96
MF 400 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	5.8 days	Standard Deviation 13.98
MF 400 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	All(mild, moderate,severe) asthma exacerbation	10.1 days	Standard Deviation 25.15
MF 400 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	3.2 days	Standard Deviation 9.16
Salmeterol/Fluticasone 50/500 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Severe asthma exacerbation	1.9 days	Standard Deviation 7.76
Salmeterol/Fluticasone 50/500 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	Moderate or severe asthma exacerbation	3.1 days	Standard Deviation 9.68
Salmeterol/Fluticasone 50/500 μg	Duration in Days of Asthma Exacerbations by Exacerbation Category	All(mild, moderate,severe) asthma exacerbation	5.1 days	Standard Deviation 14.48

Comparison: Moderate or severe asthma exacerbationp-value: <0.001van Elteren test

Comparison: Moderate or severe asthma exacerbationp-value: 0.059van Elteren test

Comparison: Severe Asthma Exacerbationp-value: 0.004Van Elteren Test

Comparison: Severe Asthma Exacerbationp-value: <0.001Van Elteren Test

Comparison: Severe asthma exacerbationp-value: 0.025van Elteren test

Comparison: All(mild, moderate, severe) Asthma Exacerbationp-value: 0.002Van Elteren Test

Comparison: All (mild, moderate, severe) Asthma Exacerbationp-value: <0.001Van Elteren Test

Comparison: All (mild, moderate, severe) asthma exacerbationp-value: 0.074van Elteren test

Secondary

Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52

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)

Population: 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	Measure	Group	Value (NUMBER)
QMF149 150/320 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 364	77.7 percentage of participants
QMF149 150/320 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 183	76.4 percentage of participants
QMF149 150/160 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 183	76.2 percentage of participants
QMF149 150/160 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 364	82.1 percentage of participants
MF 800 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 183	72.3 percentage of participants
MF 800 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 364	73.6 percentage of participants
MF 400 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 183	66.9 percentage of participants
MF 400 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 364	69.2 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 364	77.3 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52	Day 183	75.9 percentage of participants

Comparison: Day 183p-value: 0.09495% CI: [0.95, 1.81]Logistic regression model

Comparison: Day 183p-value: <0.00195% CI: [1.26, 2.37]Logistic regression model

Comparison: Day 183p-value: 0.74695% CI: [0.76, 1.46]Logistic regression model

Comparison: Day 364p-value: 0.08895% CI: [0.96, 1.87]Logistic regression model

Comparison: Day 364p-value: <0.00195% CI: [1.58, 3.17]Logistic regression model

Comparison: Day 364p-value: 0.77195% CI: [0.75, 1.49]Logistic regression model

Secondary

Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations

Time frame: Up to Week 52

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (NUMBER)
QMF149 150/320 μg	Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations	0.2 percentage of participants
QMF149 150/160 μg	Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations	0 percentage of participants
MF 800 μg	Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations	0.9 percentage of participants
MF 400 μg	Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations	1.6 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations	0.5 percentage of participants

Secondary

Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

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

Population: Safety Set consisted of all participants who received at least one dose of study medication.

Arm	Measure	Group	Value (NUMBER)
QMF149 150/320 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Adverse Events(AEs)	64.6 percentage of participants
QMF149 150/320 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Serious Adverse Events(SAEs)	4.7 percentage of participants
QMF149 150/160 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Adverse Events(AEs)	66.8 percentage of participants
QMF149 150/160 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Serious Adverse Events(SAEs)	4.6 percentage of participants
MF 800 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Adverse Events(AEs)	70.0 percentage of participants
MF 800 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Serious Adverse Events(SAEs)	4.8 percentage of participants
MF 400 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Serious Adverse Events(SAEs)	7.0 percentage of participants
MF 400 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Adverse Events(AEs)	72.2 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Adverse Events(AEs)	65.3 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Serious Adverse Events(SAEs)	4.7 percentage of participants

Secondary

Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category

The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.

Time frame: Up to Week 52

Population: FAS consisted of all patients in the RAN set who received at least one dose of study medication.

Arm	Measure	Group	Value (NUMBER)
QMF149 150/320 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Mild asthma exacerbation	13.3 percentage of participants
QMF149 150/320 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	14.9 percentage of participants
QMF149 150/320 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	25.5 percentage of participants
QMF149 150/320 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	8.1 percentage of participants
QMF149 150/320 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate asthma exacerbation	7.7 percentage of participants
QMF149 150/160 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Mild asthma exacerbation	12.1 percentage of participants
QMF149 150/160 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate asthma exacerbation	8.2 percentage of participants
QMF149 150/160 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	9.8 percentage of participants
QMF149 150/160 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	25.6 percentage of participants
QMF149 150/160 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	16.9 percentage of participants
MF 800 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate asthma exacerbation	14.3 percentage of participants
MF 800 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	26.1 percentage of participants
MF 800 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	14.5 percentage of participants
MF 800 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Mild asthma exacerbation	17.5 percentage of participants
MF 800 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	36.1 percentage of participants
MF 400 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	44.5 percentage of participants
MF 400 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	32.5 percentage of participants
MF 400 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Mild asthma exacerbation	19.6 percentage of participants
MF 400 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate asthma exacerbation	16.5 percentage of participants
MF 400 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	20.1 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate asthma exacerbation	9.2 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Mild asthma exacerbation	15.1 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	19.1 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	All (mild, moderate, severe) asthma exacerbation	30.6 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	11.9 percentage of participants

Secondary

Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes

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

Population: Safety Set consisted of all participants who received at least one dose of study medication.

Arm	Measure	Value (NUMBER)
QMF149 150/320 μg	Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes	0.7 percentage of participants
QMF149 150/160 μg	Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes	0.5 percentage of participants
MF 800 μg	Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes	1.6 percentage of participants
MF 400 μg	Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes	1.8 percentage of participants
Salmeterol/Fluticasone 50/500 μg	Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes	0.5 percentage of participants

Secondary

Post Dose FEV1 (5 Minutes-1 Hour)

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)

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 1 hour	2.343 L	Standard Error 0.01
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364:1 hour	2.414 L	Standard Error 0.0175
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 30 minutes	2.408 L	Standard Error 0.0171
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 30 minutes	2.426 L	Standard Error 0.0163
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 30 minutes	2.338 L	Standard Error 0.0095
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 5 minutes	2.413 L	Standard Error 0.0142
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:1 hour	2.456 L	Standard Error 0.0151
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 5 minutes	2.384 L	Standard Error 0.0172
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86: 30 minutes	2.436 L	Standard Error 0.0149
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 5 minutes	2.279 L	Standard Error 0.0084
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 30 minutes	2.432 L	Standard Error 0.0143
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:5 minutes	2.411 L	Standard Error 0.015
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 5 minutes	2.403 L	Standard Error 0.016
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 15 minutes	2.321 L	Standard Error 0.0088
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 1 hour	2.448 L	Standard Error 0.0145
QMF149 150/320 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 1 hour	2.432 L	Standard Error 0.0161
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 1 hour	2.440 L	Standard Error 0.0146
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 5 minutes	2.270 L	Standard Error 0.0085
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 15 minutes	2.312 L	Standard Error 0.0089
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:5 minutes	2.409 L	Standard Error 0.015
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 30 minutes	2.326 L	Standard Error 0.0096
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:1 hour	2.436 L	Standard Error 0.0151
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86: 30 minutes	2.431 L	Standard Error 0.0149
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364:1 hour	2.390 L	Standard Error 0.0172
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 1 hour	2.423 L	Standard Error 0.0162
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 30 minutes	2.427 L	Standard Error 0.0164
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 1 hour	2.347 L	Standard Error 0.0101
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 5 minutes	2.406 L	Standard Error 0.0144
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 30 minutes	2.399 L	Standard Error 0.0169
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 5 minutes	2.406 L	Standard Error 0.0161
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 30 minutes	2.426 L	Standard Error 0.0145
QMF149 150/160 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 5 minutes	2.379 L	Standard Error 0.0169
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:1 hour	2.269 L	Standard Error 0.0151
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 5 minutes	2.245 L	Standard Error 0.0172
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 30 minutes	2.253 L	Standard Error 0.0172
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 5 minutes	2.138 L	Standard Error 0.0085
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364:1 hour	2.251 L	Standard Error 0.0175
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 30 minutes	2.238 L	Standard Error 0.0146
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 1 hour	2.166 L	Standard Error 0.0101
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 5 minutes	2.224 L	Standard Error 0.0145
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 1 hour	2.257 L	Standard Error 0.0147
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:5 minutes	2.248 L	Standard Error 0.015
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 15 minutes	2.159 L	Standard Error 0.0089
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86: 30 minutes	2.257 L	Standard Error 0.0149
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 30 minutes	2.162 L	Standard Error 0.0096
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 5 minutes	2.240 L	Standard Error 0.0162
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 30 minutes	2.250 L	Standard Error 0.0165
MF 800 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 1 hour	2.253 L	Standard Error 0.0163
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:1 hour	2.188 L	Standard Error 0.0154
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 1 hour	2.183 L	Standard Error 0.0148
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 30 minutes	2.174 L	Standard Error 0.0146
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 5 minutes	2.174 L	Standard Error 0.0145
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 5 minutes	2.130 L	Standard Error 0.0173
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 5 minutes	2.163 L	Standard Error 0.0164
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 5 minutes	2.118 L	Standard Error 0.0084
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 1 hour	2.142 L	Standard Error 0.01
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364:1 hour	2.128 L	Standard Error 0.0176
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 1 hour	2.165 L	Standard Error 0.0165
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 30 minutes	2.168 L	Standard Error 0.0167
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 30 minutes	2.135 L	Standard Error 0.0172
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 15 minutes	2.137 L	Standard Error 0.0089
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86: 30 minutes	2.179 L	Standard Error 0.0152
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:5 minutes	2.178 L	Standard Error 0.0153
MF 400 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 30 minutes	2.141 L	Standard Error 0.0095
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364:1 hour	2.383 L	Standard Error 0.0171
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 5 minutes	2.224 L	Standard Error 0.0084
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 15 minutes	2.278 L	Standard Error 0.0088
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 30 minutes	2.310 L	Standard Error 0.0095
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 1: 1 hour	2.337 L	Standard Error 0.01
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 5 minutes	2.360 L	Standard Error 0.0142
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 30 minutes	2.389 L	Standard Error 0.0143
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 30: 1 hour	2.411 L	Standard Error 0.0144
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:5 minutes	2.356 L	Standard Error 0.0148
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86: 30 minutes	2.398 L	Standard Error 0.0147
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 86:1 hour	2.413 L	Standard Error 0.0149
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 5 minutes	2.359 L	Standard Error 0.016
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 30 minutes	2.386 L	Standard Error 0.0163
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 183: 1 hour	2.393 L	Standard Error 0.0161
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 5 minutes	2.358 L	Standard Error 0.0168
Salmeterol/Fluticasone 50/500 μg	Post Dose FEV1 (5 Minutes-1 Hour)	Day 364: 30 minutes	2.377 L	Standard Error 0.0167

Comparison: Day 1: 5 minutesp-value: <0.00195% CI: [0.119, 0.164]MMRM

Comparison: Day 1: 5 minutesp-value: <0.00195% CI: [0.129, 0.175]MMRM

Comparison: Day 1: 5 minutesp-value: <0.00195% CI: [0.032, 0.078]MMRM

Comparison: Day 1: 15 minutesp-value: <0.00195% CI: [0.138, 0.186]MMRM

Comparison: Day 1: 15 minutesp-value: <0.00195% CI: [0.15, 0.198]MMRM

Comparison: Day1: 15 minutesp-value: <0.00195% CI: [0.02, 0.068]MMRM

Comparison: Day 1: 30 minutesp-value: <0.00195% CI: [0.149, 0.201]MMRM

Comparison: Day 1: 30 minutesp-value: <0.00195% CI: [0.159, 0.211]MMRM

Comparison: Day 1: 30 minutesp-value: 0.03895% CI: [0.001, 0.053]MMRM

Comparison: Day 1: 1 hourp-value: <0.00195% CI: [0.15, 0.205]MMRM

Comparison: Day 1: 1hourp-value: <0.00195% CI: [0.177, 0.232]MMRM

Comparison: Day 1: 1hourp-value: 0.63295% CI: [-0.021, 0.034]MMRM

Comparison: Day 30: 5 minutesp-value: <0.00195% CI: [0.151, 0.226]MMRM

Comparison: Day 30: 5 minutesp-value: <0.00195% CI: [0.194, 0.27]MMRM

Comparison: Day 30: 5 minutesp-value: 0.00595% CI: [0.016, 0.091]MMRM

Comparison: Day 30: 30 minutesp-value: <0.00195% CI: [0.156, 0.232]MMRM

Comparison: Day 30: 30 minutesp-value: <0.00195% CI: [0.214, 0.291]MMRM

Comparison: Day 30: 30 minutesp-value: 0.02695% CI: [0.005, 0.08]MMRM

Comparison: Day 30: 1 hourp-value: <0.00195% CI: [0.152, 0.229]MMRM

Comparison: Day 30: 1 hourp-value: <0.00195% CI: [0.219, 0.296]MMRM

Comparison: Day 30: 1 hourp-value: 0.05995% CI: [-0.001, 0.075]MMRM

Comparison: Day 86: 5 minutesp-value: <0.00195% CI: [0.123, 0.203]MMRM

Comparison: Day 86: 5 minutesp-value: <0.00195% CI: [0.191, 0.271]MMRM

Comparison: Day 86: 5minutesp-value: 0.00795% CI: [0.015, 0.095]MMRM

Comparison: Day 86: 30 minutesp-value: <0.00195% CI: [0.14, 0.219]MMRM

Comparison: Day 86: 30 minutesp-value: <0.00195% CI: [0.211, 0.292]MMRM

Comparison: Day 86: 30 minutesp-value: 0.05795% CI: [-0.001, 0.078]MMRM

Comparison: Day 86: 1 hourp-value: <0.00195% CI: [0.147, 0.227]MMRM

Comparison: Day 86: 1 hourp-value: <0.00195% CI: [0.208, 0.289]MMRM

Comparison: Day 86: 1hourp-value: 0.03795% CI: [0.003, 0.083]MMRM

Comparison: Day 183: 5 minutesp-value: <0.00195% CI: [0.121, 0.206]MMRM

Comparison: Day 183: 5 minutesp-value: <0.00195% CI: [0.2, 0.286]MMRM

Comparison: Day 183: 5 minutesp-value: 0.04195% CI: [0.002, 0.087]MMRM

Comparison: Day 183: 30 minutesp-value: <0.00195% CI: [0.133, 0.22]MMRM

Comparison: Day 183: 30 minutesp-value: <0.00195% CI: [0.215, 0.303]MMRM

Comparison: Day 183: 30 minutesp-value: 0.07195% CI: [-0.003, 0.083]MMRM

Comparison: Day 183: 1 hourp-value: <0.00195% CI: [0.137, 0.223]MMRM

Comparison: Day 183: 1 hourp-value: <0.00195% CI: [0.215, 0.302]MMRM

Comparison: Day 183: 1 hourp-value: 0.07195% CI: [-0.003, 0.082]MMRM

Comparison: Day 364: 5 minutesp-value: <0.00195% CI: [0.094, 0.184]MMRM

Comparison: Day 364: 5 minutesp-value: <0.00195% CI: [0.205, 0.294]MMRM

Comparison: Day 364: 5 minutesp-value: 0.24495% CI: [-0.018, 0.071]MMRM

Comparison: Day 364: 30 minutesp-value: <0.00195% CI: [0.11, 0.2]MMRM

Comparison: Day 364: 30 minutesp-value: <0.00195% CI: [0.219, 0.308]MMRM

Comparison: Day 364: 30 minutesp-value: 0.16295% CI: [-0.013, 0.076]MMRM

Comparison: Day 364: 1 hourp-value: <0.00195% CI: [0.117, 0.209]MMRM

Comparison: Day 364: 1 hourp-value: <0.00195% CI: [0.216, 0.308]MMRM

Comparison: Day 364: 1 hourp-value: 0.18295% CI: [-0.014, 0.076]MMRM

Secondary

Pre-dose FEV1 at Weeks 4 and 12

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)

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 30	2.369 L	Standard Deviation 0.0141
QMF149 150/320 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 86	2.368 L	Standard Deviation 0.0148
QMF149 150/160 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 30	2.367 L	Standard Deviation 0.0142
QMF149 150/160 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 86	2.361 L	Standard Deviation 0.0148
MF 800 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 30	2.237 L	Standard Deviation 0.0143
MF 800 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 86	2.245 L	Standard Deviation 0.0148
MF 400 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 86	2.177 L	Standard Deviation 0.0149
MF 400 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 30	2.171 L	Standard Deviation 0.0143
Salmeterol/Fluticasone 50/500 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 30	0.2333 L	Standard Deviation 0.0141
Salmeterol/Fluticasone 50/500 μg	Pre-dose FEV1 at Weeks 4 and 12	Day 86	2.330 L	Standard Deviation 0.0146

Comparison: Day 30p-value: <0.00195% CI: [0.094, 0.17]MMRM

Comparison: Day 30p-value: <0.00195% CI: [0.158, 0.234]MMRM

Comparison: Day 30p-value: 0.06495% CI: [-0.002, 0.073]MMRM

Comparison: Day 86p-value: <0.00195% CI: [0.083, 0.162]MMRM

Comparison: Day 86p-value: <0.00195% CI: [0.144, 0.224]MMRM

Comparison: Day 86p-value: 0.06395% CI: [-0.002, 0.076]MMRM

Secondary

Rescue Medication Usage

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Rescue Medication Usage	Week1-26 Mean night-time number of puffs	-0.38 number of puffs	Standard Error 0.028
QMF149 150/320 μg	Rescue Medication Usage	Week1-26 Mean daytime number of puffs	-0.57 number of puffs	Standard Error 0.035
QMF149 150/320 μg	Rescue Medication Usage	Week1-26 Mean daily number of puffs	-0.96 number of puffs	Standard Error 0.059
QMF149 150/320 μg	Rescue Medication Usage	Week1-52 Mean night-time number of puffs	-0.40 number of puffs	Standard Error 0.029
QMF149 150/320 μg	Rescue Medication Usage	Week 1-52 Mean daytime number of puffs	-0.60 number of puffs	Standard Error 0.035
QMF149 150/320 μg	Rescue Medication Usage	Week 1-52 Mean daily number of puffs	-1.00 number of puffs	Standard Error 0.06
QMF149 150/160 μg	Rescue Medication Usage	Week 1-52 Mean daytime number of puffs	-0.51 number of puffs	Standard Error 0.035
QMF149 150/160 μg	Rescue Medication Usage	Week 1-52 Mean daily number of puffs	-0.80 number of puffs	Standard Error 0.06
QMF149 150/160 μg	Rescue Medication Usage	Week1-26 Mean night-time number of puffs	-0.27 number of puffs	Standard Error 0.028
QMF149 150/160 μg	Rescue Medication Usage	Week1-26 Mean daily number of puffs	-0.73 number of puffs	Standard Error 0.059
QMF149 150/160 μg	Rescue Medication Usage	Week1-52 Mean night-time number of puffs	-0.30 number of puffs	Standard Error 0.029
QMF149 150/160 μg	Rescue Medication Usage	Week1-26 Mean daytime number of puffs	-0.46 number of puffs	Standard Error 0.035
MF 800 μg	Rescue Medication Usage	Week1-52 Mean night-time number of puffs	-0.29 number of puffs	Standard Error 0.028
MF 800 μg	Rescue Medication Usage	Week 1-52 Mean daytime number of puffs	-0.43 number of puffs	Standard Error 0.035
MF 800 μg	Rescue Medication Usage	Week1-26 Mean night-time number of puffs	-0.26 number of puffs	Standard Error 0.028
MF 800 μg	Rescue Medication Usage	Week1-26 Mean daily number of puffs	-0.65 number of puffs	Standard Error 0.059
MF 800 μg	Rescue Medication Usage	Week1-26 Mean daytime number of puffs	-0.38 number of puffs	Standard Error 0.035
MF 800 μg	Rescue Medication Usage	Week 1-52 Mean daily number of puffs	-0.72 number of puffs	Standard Error 0.06
MF 400 μg	Rescue Medication Usage	Week1-52 Mean night-time number of puffs	-0.20 number of puffs	Standard Error 0.029
MF 400 μg	Rescue Medication Usage	Week1-26 Mean daytime number of puffs	-0.34 number of puffs	Standard Error 0.035
MF 400 μg	Rescue Medication Usage	Week1-26 Mean daily number of puffs	-0.53 number of puffs	Standard Error 0.059
MF 400 μg	Rescue Medication Usage	Week 1-52 Mean daily number of puffs	-0.56 number of puffs	Standard Error 0.06
MF 400 μg	Rescue Medication Usage	Week 1-52 Mean daytime number of puffs	-0.36 number of puffs	Standard Error 0.035
MF 400 μg	Rescue Medication Usage	Week1-26 Mean night-time number of puffs	-0.19 number of puffs	Standard Error 0.028
Salmeterol/Fluticasone 50/500 μg	Rescue Medication Usage	Week 1-52 Mean daytime number of puffs	-0.55 number of puffs	Standard Error 0.035
Salmeterol/Fluticasone 50/500 μg	Rescue Medication Usage	Week1-26 Mean daily number of puffs	-0.87 number of puffs	Standard Error 0.059
Salmeterol/Fluticasone 50/500 μg	Rescue Medication Usage	Week1-26 Mean daytime number of puffs	-0.53 number of puffs	Standard Error 0.035
Salmeterol/Fluticasone 50/500 μg	Rescue Medication Usage	Week 1-52 Mean daily number of puffs	-0.91 number of puffs	Standard Error 0.06
Salmeterol/Fluticasone 50/500 μg	Rescue Medication Usage	Week1-52 Mean night-time number of puffs	-0.35 number of puffs	Standard Error 0.029
Salmeterol/Fluticasone 50/500 μg	Rescue Medication Usage	Week1-26 Mean night-time number of puffs	-0.34 number of puffs	Standard Error 0.028

Comparison: Week1-26 Mean night-time number of puffsp-value: 0.00195% CI: [-0.2, -0.05]LMM

Comparison: Week 1-26 Mean night-time number of puffsp-value: 0.03595% CI: [-0.16, -0.01]LMM

Comparison: Week 1-26 Mean night-time number of puffsp-value: 0.26195% CI: [-0.12, 0.03]LMM

Comparison: Week 1-26 Mean daytime number of puffsp-value: <0.00195% CI: [-0.28, -0.09]LMM

Comparison: Week 1-26 Mean daytime number of puffsp-value: 0.01195% CI: [-0.21, -0.03]LMM

Comparison: Week 1-26 Mean daytime number of puffsp-value: 0.42595% CI: [-0.13, 0.06]LMM

Comparison: Week 1-26 Mean daily number of puffsp-value: <0.00195% CI: [-0.46, -0.15]LMM

Comparison: Week 1-26 Mean daily number of puffsp-value: 0.01795% CI: [-0.35, -0.03]LMM

Comparison: Week 1-26 Mean daily number of puffsp-value: 0.2995% CI: [-0.24, -0.07]LMM

Comparison: Week 1-52 Mean night-time number of puffsp-value: 0.00495% CI: [-0.19, -0.04]LMM

Comparison: Week 1-52 Mean night-time number of puffsp-value: 0.01995% CI: [-0.17, -0.02]LMM

Comparison: Week 1-52 Mean night-time number of puffsp-value: 0.22695% CI: [-0.12, 0.03]LMM

Comparison: Week 1-52 Mean daytime number of puffsp-value: <0.00195% CI: [-0.26, -0.07]LMM

Comparison: Week 1-52 Mean daytime number of puffsp-value: 0.00295% CI: [-0.24, -0.05]LMM

Comparison: Week 1-52 Mean daytime number of puffsp-value: 0.38495% CI: [-0.14, 0.05]LMM

Comparison: Week 1-52 Mean daily number of puffsp-value: <0.00195% CI: [-0.44, -0.12]LMM

Comparison: Week 1-52 Mean daily number of puffsp-value: 0.00495% CI: [-0.39, -0.07]LMM

Comparison: Week 1-52 Mean daily number of puffsp-value: 0.24595% CI: [-0.25, 0.06]LMM

Secondary

Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations

The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.

Time frame: Up to Week 52

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (MEDIAN)
QMF149 150/320 μg	Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations	367.0 days
QMF149 150/160 μg	Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations	367.0 days
MF 800 μg	Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations	367.0 days
MF 400 μg	Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations	366.0 days
Salmeterol/Fluticasone 50/500 μg	Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations	367.0 days

p-value: 0.22295% CI: [0.03, 2.29]Regression, Cox

p-value: 0.992Regression, Cox

p-value: 0.61895% CI: [0.05, 6.01]Regression, Cox

Secondary

Time to First Asthma Exacerbation by Exacerbation Category

The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.

Time frame: Up to Week 52

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Group	Value (MEDIAN)
QMF149 150/320 μg	Time to First Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	366.0 days
QMF149 150/320 μg	Time to First Asthma Exacerbation by Exacerbation Category	All (mild, moderate or severe) asthma exacerbation	366.0 days
QMF149 150/320 μg	Time to First Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	367 days
QMF149 150/160 μg	Time to First Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	366 days
QMF149 150/160 μg	Time to First Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	366.0 days
QMF149 150/160 μg	Time to First Asthma Exacerbation by Exacerbation Category	All (mild, moderate or severe) asthma exacerbation	366.0 days
MF 800 μg	Time to First Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	366 days
MF 800 μg	Time to First Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	366.0 days
MF 800 μg	Time to First Asthma Exacerbation by Exacerbation Category	All (mild, moderate or severe) asthma exacerbation	364.5 days
MF 400 μg	Time to First Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	364.0 days
MF 400 μg	Time to First Asthma Exacerbation by Exacerbation Category	All (mild, moderate or severe) asthma exacerbation	306.0 days
MF 400 μg	Time to First Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	366 days
Salmeterol/Fluticasone 50/500 μg	Time to First Asthma Exacerbation by Exacerbation Category	Severe asthma exacerbation	366 days
Salmeterol/Fluticasone 50/500 μg	Time to First Asthma Exacerbation by Exacerbation Category	Moderate or severe asthma exacerbation	366.0 days
Salmeterol/Fluticasone 50/500 μg	Time to First Asthma Exacerbation by Exacerbation Category	All (mild, moderate or severe) asthma exacerbation	365.0 days

Comparison: Moderate or severe asthma exacerbationp-value: <0.00195% CI: [0.39, 0.72]Regression, Cox

Comparison: Moderate or severe asthma exacerbationp-value: <0.00195% CI: [0.34, 0.6]Regression, Cox

Comparison: Moderate or severe asthma exacerbationp-value: 0.20995% CI: [0.59, 1.12]Regression, Cox

Comparison: Severe asthma exacerbationp-value: 0.00395% CI: [0.36, 0.81]Regression, Cox

Comparison: Severe asthma exacerbationp-value: <0.00195% CI: [0.3, 0.63]Regression, Cox

Comparison: Severe asthma exacerbationp-value: 0.11595% CI: [0.47, 1.09]Regression, Cox

Comparison: All asthma exacerbationp-value: <0.00195% CI: [0.51, 0.82]Regression, Cox

Comparison: All asthma exacerbationp-value: <0.00195% CI: [0.38, 0.6]Regression, Cox

Comparison: All asthma exacerbationp-value: 0.18595% CI: [0.66, 1.08]Regression, Cox

Secondary

Time to First Hospitalization for Asthma Exacerbation

The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.

Time frame: Up to Week 52

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (MEDIAN)
QMF149 150/320 μg	Time to First Hospitalization for Asthma Exacerbation	367.0 days
QMF149 150/160 μg	Time to First Hospitalization for Asthma Exacerbation	367.0 days
MF 800 μg	Time to First Hospitalization for Asthma Exacerbation	367.0 days
MF 400 μg	Time to First Hospitalization for Asthma Exacerbation	366.0 days
Salmeterol/Fluticasone 50/500 μg	Time to First Hospitalization for Asthma Exacerbation	367.0 days

p-value: 0.33795% CI: [0.13, 2.03]Regression, Cox

p-value: 0.06395% CI: [0.02, 1.11]Regression, Cox

p-value: 0.59995% CI: [0.27, 9.7]Regression, Cox

Secondary

Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations

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

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (MEAN)	Dispersion
QMF149 150/320 μg	Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations	26.0 milligrams	Standard Deviation 136.92
QMF149 150/160 μg	Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations	29.9 milligrams	Standard Deviation 124.98
MF 800 μg	Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations	28.0 milligrams	Standard Deviation 95.18
MF 400 μg	Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations	47.8 milligrams	Standard Deviation 139.98
Salmeterol/Fluticasone 50/500 μg	Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations	26.9 milligrams	Standard Deviation 114.36

Secondary

Trough FEV1 at Week 52

Time frame: Week 52

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Trough FEV1 at Week 52	2.386 L	Standard Error 0.0168
QMF149 150/160 μg	Trough FEV1 at Week 52	2.357 L	Standard Error 0.0167
MF 800 μg	Trough FEV1 at Week 52	2.249 L	Standard Error 0.017
MF 400 μg	Trough FEV1 at Week 52	2.148 L	Standard Error 0.017
Salmeterol/Fluticasone 50/500 μg	Trough FEV1 at Week 52	2.338 L	Standard Error 0.0167

p-value: <0.00195% CI: [0.09, 0.183]MMRM

p-value: <0.00195% CI: [0.163, 0.255]MMRM

p-value: 0.0495% CI: [0.002, 0.094]MMRM

Secondary

Trough FEV1 Measured After 26 Weeks of Treatment

Time frame: Week 26

Population: FAS consisted of all participants in the RAN set who received at least one dose of study medication.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Trough FEV1 Measured After 26 Weeks of Treatment	2.383 L	Standard Error 0.0159
QMF149 150/160 μg	Trough FEV1 Measured After 26 Weeks of Treatment	2.387 L	Standard Error 0.016
MF 800 μg	Trough FEV1 Measured After 26 Weeks of Treatment	2.250 L	Standard Error 0.0162
MF 400 μg	Trough FEV1 Measured After 26 Weeks of Treatment	2.176 L	Standard Error 0.0162
Salmeterol/Fluticasone 50/500 μg	Trough FEV1 Measured After 26 Weeks of Treatment	2.346 L	Standard Error 0.016

p-value: 0.10195% CI: [-0.007, 0.08]MMRM

Secondary

Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)

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)

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 2	1.644 Litres/second (L/s)	Standard Error 0.0186
QMF149 150/320 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 365	1.745 Litres/second (L/s)	Standard Error 0.0259
QMF149 150/320 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 184	1.775 Litres/second (L/s)	Standard Error 0.0249
QMF149 150/160 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 184	1.738 Litres/second (L/s)	Standard Error 0.025
QMF149 150/160 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 2	1.617 Litres/second (L/s)	Standard Error 0.0187
QMF149 150/160 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 365	1.686 Litres/second (L/s)	Standard Error 0.0257
MF 800 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 2	1.455 Litres/second (L/s)	Standard Error 0.0191
MF 800 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 184	1.546 Litres/second (L/s)	Standard Error 0.0253
MF 800 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 365	1.530 Litres/second (L/s)	Standard Error 0.0261
MF 400 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 2	1.406 Litres/second (L/s)	Standard Error 0.0186
MF 400 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 365	1.440 Litres/second (L/s)	Standard Error 0.0261
MF 400 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 184	1.473 Litres/second (L/s)	Standard Error 0.0254
Salmeterol/Fluticasone 50/500 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 184	1.692 Litres/second (L/s)	Standard Error 0.025
Salmeterol/Fluticasone 50/500 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 2	1.662 Litres/second (L/s)	Standard Error 0.0189
Salmeterol/Fluticasone 50/500 μg	Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)	Day 365	1.692 Litres/second (L/s)	Standard Error 0.0258

Comparison: Day 2p-value: <0.00195% CI: [0.139, 0.238]MMRM

Comparison: Day 2p-value: <0.00195% CI: [0.161, 0.259]MMRM

Comparison: Day 2p-value: 0.47595% CI: [-0.067, 0.031]MMRM

Comparison: Day 184p-value: <0.00195% CI: [0.161, 0.296]MMRM

Comparison: Day 184p-value: <0.00195% CI: [0.197, 0.333]MMRM

Comparison: Day 184p-value: 0.01595% CI: [0.016, 0.151]MMRM

Comparison: Day 365p-value: <0.00195% CI: [0.145, 0.285]MMRM

Comparison: Day 365p-value: <0.00195% CI: [0.176, 0.316]MMRM

Comparison: Day 365p-value: 0.13995% CI: [-0.017, 0.122]MMRM

Secondary

Trough Forced Vital Capacity (FVC)

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)

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
QMF149 150/320 μg	Trough Forced Vital Capacity (FVC)	Day 2	3.342 L	Standard Error 0.0173
QMF149 150/320 μg	Trough Forced Vital Capacity (FVC)	Day 365	3.394 L	Standard Error 0.0182
QMF149 150/320 μg	Trough Forced Vital Capacity (FVC)	Day 184	3.372 L	Standard Error 0.0179
QMF149 150/160 μg	Trough Forced Vital Capacity (FVC)	Day 184	3.387 L	Standard Error 0.018
QMF149 150/160 μg	Trough Forced Vital Capacity (FVC)	Day 2	3.342 L	Standard Error 0.0174
QMF149 150/160 μg	Trough Forced Vital Capacity (FVC)	Day 365	3.364 L	Standard Error 0.0181
MF 800 μg	Trough Forced Vital Capacity (FVC)	Day 184	3.322 L	Standard Error 0.0183
MF 800 μg	Trough Forced Vital Capacity (FVC)	Day 2	3.256 L	Standard Error 0.0177
MF 800 μg	Trough Forced Vital Capacity (FVC)	Day 365	3.319 L	Standard Error 0.0184
MF 400 μg	Trough Forced Vital Capacity (FVC)	Day 2	3.203 L	Standard Error 0.0173
MF 400 μg	Trough Forced Vital Capacity (FVC)	Day 365	3.218 L	Standard Error 0.0183
MF 400 μg	Trough Forced Vital Capacity (FVC)	Day 184	3.246 L	Standard Error 0.0182
Salmeterol/Fluticasone 50/500 μg	Trough Forced Vital Capacity (FVC)	Day 184	3.355 L	Standard Error 0.018
Salmeterol/Fluticasone 50/500 μg	Trough Forced Vital Capacity (FVC)	Day 2	3.344 L	Standard Error 0.0176
Salmeterol/Fluticasone 50/500 μg	Trough Forced Vital Capacity (FVC)	Day 365	3.358 L	Standard Error 0.0182

Comparison: Day 2p-value: <0.00195% CI: [0.04, 0.133]MMRM

Comparison: Day 2p-value: <0.00195% CI: [0.093, 0.185]MMRM

Comparison: Day 2p-value: 0.92795% CI: [-0.049, 0.044]MMRM

Comparison: Day 184p-value: 0.04495% CI: [0.001, 0.098]MMRM

Comparison: Day 184p-value: <0.00195% CI: [0.093, 0.19]MMRM

Comparison: Day 184p-value: 0.4995% CI: [-0.031, 0.065]MMRM

Comparison: Day 365p-value: 0.00295% CI: [0.027, 0.125]MMRM

Comparison: Day 365p-value: <0.00195% CI: [0.098, 0.195]MMRM

Comparison: Day 365p-value: 0.14395% CI: [-0.012, 0.085]MMRM

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026

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

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Trough Forced Expiratory Volume in One Second (Trough FEV1) at Week 26

Annual Rate of Asthma Exacerbations by Exacerbation Category

Asthma Control Questionnaire (ACQ-7) at Weeks 4, 12, 26 and 52

Asthma Quality of Life Questionnaire (AQLQ)

Change Form Baseline in Percentage of Days With no Daytime Symptoms

Change Form Baseline in Percentage of Mornings With no Symptoms on Awakening

Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment

Change From Baseline in Percentage of Asthma Symptoms Free Days

Change From Baseline in Percentage of Nights With no Night-time Awakenings

Change From Baseline in Percentage of Rescue Medication Free Days

Duration in Days of Asthma Exacerbations by Exacerbation Category

Percentage of Participants Achieving the Minimal Important Difference (MID) ACQ ≥ 0.5 at Weeks 26 and 52

Percentage of Participants Who Permanently Discontinued Study Medication Due to Asthma Exacerbations

Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category

Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes

Post Dose FEV1 (5 Minutes-1 Hour)

Pre-dose FEV1 at Weeks 4 and 12

Rescue Medication Usage

Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbations

Time to First Asthma Exacerbation by Exacerbation Category

Time to First Hospitalization for Asthma Exacerbation

Total Amounts of Systemic Corticosteroids (in Doses) Used to Treat Asthma Exacerbations

Trough FEV1 at Week 52

Trough FEV1 Measured After 26 Weeks of Treatment

Trough Forced Expiratory Flow (FEF)Between 25% and 75% of FVC (FEF25-75)

Trough Forced Vital Capacity (FVC)