Mild Asthma
Conditions
Keywords
Phase III, blinded, QMF149, Mometasone furoate (MF), mild asthma, Adolescent, adult
Brief summary
The purpose of the trial was to evaluate efficacy and safety of QMF149 150/80 microgram o.d. delivered via Concept1 compared to MF 200 microgram o.d., delivered via Twisthaler® in terms of lung function and symptom control in poorly (ie inadequately) controlled asthma patients. This study was to assess contribution of LABA as an add-on therapy to low dose ICS monotherapy.
Detailed description
The primary objective of this study was to demonstrate the superiority of QMF149 150/80 microgram o.d. (in the evening) delivered via Concept1 compared with MF 200 microgram o.d. (in the evening) delivered via Twisthaler® in terms of trough FEV1 after 12 weeks of treatment in adults and adolescents. The key secondary objective of this study was to demonstrate the superiority of QMF149 150/80 microgram to MF 200 microgram o.d. in terms of ACQ-7 after 12 weeks of treatment.
Interventions
DRUGQMF149 150/80 μg
QMF149 150/80 μg o.d via Concept1
DRUGMF 200 μg
MF 200 μg o.d. via Twisthaler®
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a documented diagnosis of asthma for a period of at least 3 months prior to Screening Visit * Patients who have used low dose ICS , with or without controller (ie, LABA, Leukotriene Receptor Antagonist ) at stable dose for at least 1 month prior to Screening Visit * Adult patients who are symptomatic at screening despite treatment with existing therapy. Patients with ACQ-7 score ≥ 1.5 at Visit 101 and at Visit 102 (inadequately controlled). * Adolescent patients : * If taking only ICS (without LABA) and are symptomatic at screening despite treatment with low doses of ICS. These patients must have ACQ-7 score ≥ 1.5 at Visit 101 and at Visit 102 . * If taking ICS (low dose)/ LABA, and have ACQ-7 score ≥1 and \<1.5 at Visit 101: they must have ACQ-7 score≥1.5 at Visit 102 ( prior to randomization). * Pre-bronchodilator FEV1≥ 60 % and \< 90 % of the predicted normal value for the patient after withholding bronchodilators at both Visits 101 and 102 * Patients who demonstrate an increase in FEV1 of 12% and ≥ 200 mL within 30 minutes after administration of 400 microgram salbutamol/360 microgram albuterol (or equivalent dose) at Visit 101.
Exclusion criteria
* Patients who have smoked or inhaled tobacco products (including electronic cigarettes) within the 6 month period prior to Visit 1, or who have a smoking history of greater than or equal to 10 pack year. * Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization (\> 24 hours) or emergency room visit (≤ 24 hours) as follows: * For adults: within 6 weeks of Screening Visit. If patients experience an asthma attack/exacerbation requiring systemic steroids or emergency room visit between Visit 1 and Visit 102 they may be re-screened 6 weeks after recovery from the exacerbation * For adolescents: Severe asthma attack/exacerbation requiring systemic corticosteroids in the last 6 months, OR hospitalization (\> 24 hours) due to severe asthma attack/exacerbation requiring systemic corticosteroids in the last 6 months, OR emergency room visit (≤ 24 hours) due to severe asthma attack/exacerbation requiring systemic corticosteroids within the last 6 months. * Patients who ever required intubation for a severe asthma attack/exacerbation * Patients with a clinical condition (eg. glaucoma, cataract and fragility fractures) which may be worsened by ICS administration (according to investigator's medical judgment ) * Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Screening Visit or between Visit 1and Visit 102. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening. * Patients with any chronic conditions affecting the upper respiratory tract (eg. chronic sinusitis) which in the opinion of the investigator may interfere with the study. * Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis. * Patients with Type I diabetes or uncontrolled Type II diabetes. * Patients with narcolepsy and/or insomnia. * Patients on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout the course of the study. * Patients with diagnosed rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption or with known intolerance to lactose or milk products. * Patients who use a long acting muscarinic antagonist (LAMA) within 3 months prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 | week 12 | demonstrate the superiority of QMF149 150/80 microgram o.d. (in the evening) delivered via Concept1 compared with MF 200 microgram o.d. (in the evening) delivered via Twisthaler® in terms of trough FEV1 after 12 weeks of treatment in adults and adolescents. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured by spirometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACQ-7 | week 12 | ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control. the ACQ-7 was used to assess improvements in asthma symptom control. The ACQ-7, a seven-item disease-specific instrument developed and validated to assess asthma control in patients in clinical trials as well as in individuals in clinical practice, was provided to the site. All seven items were then scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating no control. The questions were equally weighted and the total score was the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the patient while the last question (question 7) was completed by the study investigator using spirometry data generated by the spirometry equipment. |
| Trough FEV1 at Day 2 | Day 2 | Forced Expiratory Volume in 1 second (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 Week 4 | week 4 | Pre-dose FEV1 is defined as the mean of -45 min and -15 min FEV1 values pre-evening dose |
| PEF Over 4 and 12 Weeks | week 12 | Morning and Evening Peak Expiratory Flow Rate (PEF) will be measured. PEF is the peak expiratory flow, the maximum speed of expiration |
| Percentage of Patients With ACQ-7 MID at Week 12 | week 12 | MID is Minimum Important Difference. ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control. Percent of patients achieving the minimal important difference (MID) in ACQ-7 (i.e. at least 0.5 decrease from baseline) will be measured. |
| Daily E-diary Over 12 Weeks | week 12 | Percentage of asthma symptoms free days, the percentage of nights without nighttime awakenings, and the percentage of mornings without symptoms on awakening as recorded by daily electronic Diary (e-Diary) over 12 weeks of treatment |
| FVC Over 12 Weeks | week 12 | FVC is the total amount of air exhaled during the FEV test. Forced Vital Capacity (FVC) and Forced Expiratory Flow between 25% and 75% of FVC (FEF25-75) will be measured |
| Rescue Medication Use Over 12 Weeks | week 12 | Rescue salbutamol/albuterol usage (mean daily, nighttime and daytime use) from e-Diary recordings over 12 weeks of treatment |
| Percentage of Rescue Medication Free Days Over 12 Weeks | week 12 | Percentage of rescue medication free days over 12 weeks of treatment period |
| Quality of Life Assessed by Asthma Quality of Life Questionnaire AQLQ-S 12 | week 12 | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and \> 1.5 as marked clinically important differences for any individual domain or for the overall summary score. |
| Number of Patients With Asthma Exacerbation Over 12 Weeks | Week 12 | The exacerbation categories are: mild, moderate, severe and the combination of moderate or severe. Time to first asthma exacerbation by exacerbation category. Annual rate of asthma exacerbations by exacerbation category. |
| The Number of Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | Week 12 | Annual incidence rate of asthma exacerbation by severity of exacerbation. The number of asthma exacerbation is used to calculate annual incidence rate. A severe asthma exacerbation is SCS (Systemic Corticosteroids) use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations |
| Number of Patients With First Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | Week 12 | The annual rate of asthma exacerbations were analyzed using a generalized linear model. |
| ACQ-7 at Week 4 | week 4 | ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control |
Countries
Bulgaria, Chile, Colombia, Estonia, Germany, Hungary, India, Italy, Japan, Latvia, Lithuania, Malaysia, Peru, Philippines, Poland, Russia, Slovakia, South Africa, South Korea, Sweden, Thailand, Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| QMF149 150/80 μg QMF149 150/80 microgram o.d. delivered via Concept1 | 398 |
| MF 200 µg MF 200 microgram o.d. delivered via Twisthaler® | 404 |
| Total | 802 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 8 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance with study treatment | 0 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol deviation | 3 | 4 |
| Overall Study | Subject/guardian decision | 0 | 4 |
| Overall Study | Technical problems | 0 | 1 |
Baseline characteristics
| Characteristic | MF 200 µg | Total | QMF149 150/80 μg |
|---|---|---|---|
| Age, Continuous | 45.1 Years STANDARD_DEVIATION 16.27 | 45.6 Years STANDARD_DEVIATION 16.26 | 46.1 Years STANDARD_DEVIATION 16.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 101 Participants | 199 Participants | 98 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 33 Participants | 70 Participants | 37 Participants |
| Race (NIH/OMB) White | 265 Participants | 527 Participants | 262 Participants |
| Sex: Female, Male Female | 241 Participants | 488 Participants | 247 Participants |
| Sex: Female, Male Male | 163 Participants | 314 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 396 | 0 / 399 |
| other Total, other adverse events | 69 / 396 | 106 / 399 |
| serious Total, serious adverse events | 5 / 396 | 7 / 399 |
Outcome results
Primary
Trough FEV1
demonstrate the superiority of QMF149 150/80 microgram o.d. (in the evening) delivered via Concept1 compared with MF 200 microgram o.d. (in the evening) delivered via Twisthaler® in terms of trough FEV1 after 12 weeks of treatment in adults and adolescents. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured by spirometry.
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | Trough FEV1 | 2.562 Liters | Standard Error 0.0134 |
| MF 200 µg | Trough FEV1 | 2.379 Liters | Standard Error 0.0134 |
p-value: <0.00195% CI: [0.148, 0.217]Mixed Models Analysis
Secondary
ACQ-7
ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control. the ACQ-7 was used to assess improvements in asthma symptom control. The ACQ-7, a seven-item disease-specific instrument developed and validated to assess asthma control in patients in clinical trials as well as in individuals in clinical practice, was provided to the site. All seven items were then scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating no control. The questions were equally weighted and the total score was the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the patient while the last question (question 7) was completed by the study investigator using spirometry data generated by the spirometry equipment.
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | ACQ-7 | 1.323 Units on a scale | Standard Error 0.0411 |
| MF 200 µg | ACQ-7 | 1.540 Units on a scale | Standard Error 0.0411 |
p-value: <0.00195% CI: [-0.293, -0.143]Mixed Models Analysis
Secondary
ACQ-7 at Week 4
ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control
Time frame: week 4
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | ACQ-7 at Week 4 | 1.454 Units on a scale | Standard Error 0.0408 |
| MF 200 µg | ACQ-7 at Week 4 | 1.658 Units on a scale | Standard Error 0.0406 |
p-value: <0.00195% CI: [-0.277, -0.131]Mixed Models Analysis
Secondary
Daily E-diary Over 12 Weeks
Percentage of asthma symptoms free days, the percentage of nights without nighttime awakenings, and the percentage of mornings without symptoms on awakening as recorded by daily electronic Diary (e-Diary) over 12 weeks of treatment
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 150/80 μg | Daily E-diary Over 12 Weeks | % of nights with no night-time awakenings | 13.4 Percentage | Standard Error 1.37 |
| QMF149 150/80 μg | Daily E-diary Over 12 Weeks | % of mornings with no symptoms on awakening | 14.7 Percentage | Standard Error 1.53 |
| QMF149 150/80 μg | Daily E-diary Over 12 Weeks | % of asthma symptom-free days | 17.1 Percentage | Standard Error 1.68 |
| MF 200 µg | Daily E-diary Over 12 Weeks | % of nights with no night-time awakenings | 8.7 Percentage | Standard Error 1.36 |
| MF 200 µg | Daily E-diary Over 12 Weeks | % of mornings with no symptoms on awakening | 11.2 Percentage | Standard Error 1.53 |
| MF 200 µg | Daily E-diary Over 12 Weeks | % of asthma symptom-free days | 14.4 Percentage | Standard Error 1.65 |
Secondary
FVC Over 12 Weeks
FVC is the total amount of air exhaled during the FEV test. Forced Vital Capacity (FVC) and Forced Expiratory Flow between 25% and 75% of FVC (FEF25-75) will be measured
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 150/80 μg | FVC Over 12 Weeks | Pre dose trough FVC (n=383,379) | 3.453 Liters | Standard Error 0.0169 |
| QMF149 150/80 μg | FVC Over 12 Weeks | Pre-dose trough FEF25-75% (n=383,379) | 2.030 Liters | Standard Error 0.0228 |
| MF 200 µg | FVC Over 12 Weeks | Pre dose trough FVC (n=383,379) | 3.353 Liters | Standard Error 0.0169 |
| MF 200 µg | FVC Over 12 Weeks | Pre-dose trough FEF25-75% (n=383,379) | 1.742 Liters | Standard Error 0.0228 |
Comparison: Pre-dose trough FVCp-value: <0.00195% CI: [0.061, 0.139]Mixed Models Analysis
Comparison: Pre-dose trough FEF25-75%p-value: <0.00195% CI: [0.231, 0.345]Mixed Models Analysis
Secondary
Number of Patients With Asthma Exacerbation Over 12 Weeks
The exacerbation categories are: mild, moderate, severe and the combination of moderate or severe. Time to first asthma exacerbation by exacerbation category. Annual rate of asthma exacerbations by exacerbation category.
Time frame: Week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QMF149 150/80 μg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Mild asthma exacerbation | 11 Number of patients |
| QMF149 150/80 μg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Moderate asthma exacerbation | 7 Number of patients |
| QMF149 150/80 μg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Severe asthma exacerbation | 3 Number of patients |
| QMF149 150/80 μg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Moderate or severe asthma exacerbation | 10 Number of patients |
| MF 200 µg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Moderate or severe asthma exacerbation | 32 Number of patients |
| MF 200 µg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Mild asthma exacerbation | 29 Number of patients |
| MF 200 µg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Severe asthma exacerbation | 11 Number of patients |
| MF 200 µg | Number of Patients With Asthma Exacerbation Over 12 Weeks | Moderate asthma exacerbation | 23 Number of patients |
Secondary
Number of Patients With First Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period
The annual rate of asthma exacerbations were analyzed using a generalized linear model.
Time frame: Week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QMF149 150/80 μg | Number of Patients With First Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | 10 Count of participants |
| MF 200 µg | Number of Patients With First Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | 32 Count of participants |
p-value: <0.00195% CI: [0.14, 0.59]Regression, Cox
Secondary
PEF Over 4 and 12 Weeks
Morning and Evening Peak Expiratory Flow Rate (PEF) will be measured. PEF is the peak expiratory flow, the maximum speed of expiration
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 150/80 μg | PEF Over 4 and 12 Weeks | Mean Morning PEF (n=382,382) | 31.0 L/min | Standard Error 1.98 |
| QMF149 150/80 μg | PEF Over 4 and 12 Weeks | Mean Evening PEF (n=386,386) | 26.8 L/min | Standard Error 1.84 |
| MF 200 µg | PEF Over 4 and 12 Weeks | Mean Morning PEF (n=382,382) | 3.8 L/min | Standard Error 1.97 |
| MF 200 µg | PEF Over 4 and 12 Weeks | Mean Evening PEF (n=386,386) | 0.7 L/min | Standard Error 1.84 |
Comparison: Mean Morning PEFp-value: <0.00195% CI: [22.1, 32.4]Mixed Models Analysis
Comparison: Mean Evening PEFp-value: <0.00195% CI: [21, 31.2]Mixed Models Analysis
Secondary
Percentage of Patients With ACQ-7 MID at Week 12
MID is Minimum Important Difference. ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control. Percent of patients achieving the minimal important difference (MID) in ACQ-7 (i.e. at least 0.5 decrease from baseline) will be measured.
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QMF149 150/80 μg | Percentage of Patients With ACQ-7 MID at Week 12 | 74.7 Percentage |
| MF 200 µg | Percentage of Patients With ACQ-7 MID at Week 12 | 64.9 Percentage |
Secondary
Percentage of Rescue Medication Free Days Over 12 Weeks
Percentage of rescue medication free days over 12 weeks of treatment period
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | Percentage of Rescue Medication Free Days Over 12 Weeks | 22.2 Percentage | Standard Error 1.81 |
| MF 200 µg | Percentage of Rescue Medication Free Days Over 12 Weeks | 14.1 Percentage | Standard Error 1.8 |
p-value: <0.00195% CI: [4.3, 11.8]Mixed Models Analysis
Secondary
Pre-dose FEV1 at Week 4
Pre-dose FEV1 is defined as the mean of -45 min and -15 min FEV1 values pre-evening dose
Time frame: week 4
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | Pre-dose FEV1 at Week 4 | 2.545 Liters | Standard Error 0.0132 |
| MF 200 µg | Pre-dose FEV1 at Week 4 | 2.369 Liters | Standard Error 0.0131 |
p-value: <0.00195% CI: [0.145, 0.207]Mixed Models Analysis
Secondary
Quality of Life Assessed by Asthma Quality of Life Questionnaire AQLQ-S 12
The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and \> 1.5 as marked clinically important differences for any individual domain or for the overall summary score.
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | Quality of Life Assessed by Asthma Quality of Life Questionnaire AQLQ-S 12 | 5.779 Score | Standard Error 0.0475 |
| MF 200 µg | Quality of Life Assessed by Asthma Quality of Life Questionnaire AQLQ-S 12 | 5.630 Score | Standard Error 0.0473 |
p-value: <0.00195% CI: [0.064, 0.234]Mixed Models Analysis
Secondary
Rescue Medication Use Over 12 Weeks
Rescue salbutamol/albuterol usage (mean daily, nighttime and daytime use) from e-Diary recordings over 12 weeks of treatment
Time frame: week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 150/80 μg | Rescue Medication Use Over 12 Weeks | Night-time number of puffs of rescue medication | -0.26 Number of puffs of rescue medication | Standard Error 0.025 |
| QMF149 150/80 μg | Rescue Medication Use Over 12 Weeks | Daytime number of puffs of rescue medication | -0.39 Number of puffs of rescue medication | Standard Error 0.033 |
| MF 200 µg | Rescue Medication Use Over 12 Weeks | Night-time number of puffs of rescue medication | -0.16 Number of puffs of rescue medication | Standard Error 0.025 |
| MF 200 µg | Rescue Medication Use Over 12 Weeks | Daytime number of puffs of rescue medication | -0.24 Number of puffs of rescue medication | Standard Error 0.032 |
Comparison: Night-time number of puffs of rescue medicationp-value: <0.00195% CI: [-0.16, -0.05]Mixed Models Analysis
Comparison: Daytime number of puffs of rescue medicationp-value: <0.00195% CI: [-0.22, -0.08]Mixed Models Analysis
Secondary
The Number of Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period
Annual incidence rate of asthma exacerbation by severity of exacerbation. The number of asthma exacerbation is used to calculate annual incidence rate. A severe asthma exacerbation is SCS (Systemic Corticosteroids) use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations
Time frame: Week 12
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QMF149 150/80 μg | The Number of Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | Moderate or severe asthma exacerbation | 0.08 Number of exacerbation |
| QMF149 150/80 μg | The Number of Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | All (mild, moderate, severe) asthma exacerbation | 0.20 Number of exacerbation |
| MF 200 µg | The Number of Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | Moderate or severe asthma exacerbation | 0.31 Number of exacerbation |
| MF 200 µg | The Number of Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period | All (mild, moderate, severe) asthma exacerbation | 0.67 Number of exacerbation |
Secondary
Trough FEV1 at Day 2
Forced Expiratory Volume in 1 second (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: Day 2
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN set who received at least one dose of study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 150/80 μg | Trough FEV1 at Day 2 | 2.490 Liters | Standard Error 0.0108 |
| MF 200 µg | Trough FEV1 at Day 2 | 2.358 Liters | Standard Error 0.0108 |
p-value: <0.00195% CI: [0.105, 0.158]Mixed Models Analysis