Asthma
Conditions
Brief summary
This is a randomized, multi-center, double-blind, double-dummy, placebo-controlled, parallel-group study, evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) versus MF for 26 weeks. Prior to the 26-week double-blind Treatment Period, participants will receive open-label (OL) MF MDI 100 mcg twice daily (BID) for 2 to 3 weeks during the Run-in Period. Efficacy will be measured by the Area Under the Curve from 0 to 12 hours \[AUC\](0-12 hours) of the change from Baseline to the Week 12 Endpoint in Forced Expiratory Volume in One Second (FEV1) and by the time-to-first severe asthma exacerbation across the 26-week treatment period.
Interventions
DRUGMometasone Furoate/Formoterol Fumarate Combination MDI 100/10 mcg BID
MF/F 100/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks
MF 100 mcg via metered dose inhaler twice daily for 26 weeks
F via metered dose inhaler 10 mcg twice a day for 26 weeks
DRUGPlacebo
Placebo metered dose inhaler twice a day for 26 weeks
Sponsors
Novartis
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>=12 years, either sex, any race, asthma diagnosis \>=12 months that is consistent with the following: Diagnosis based on clinical history & examination, pulmonary function parameters & response to beta-2-agonists, according to international guidelines. * Been using low daily dose of inhaled corticosteroid (ICS) (either alone or in combination with long-acting beta agonist \[LABA\]) \>=12 weeks & been on stable asthma regimen for \>=2 weeks prior to Screening. Low daily doses of ICS are: 200-500 mcg beclomethasone chlorofluorocarbon (CFC), 100-250 mcg beclomethasone hydrofluoroalkane (HFA), 200-600 mcg budesonide dry powder inhaler (DPI), 500-1000 mcg flunisolide, 100-250 mcg fluticasone, 200 mcg MF, 400-1000 mcg triamcinolone acetonide, 80 to 160 mcg ciclesonide. Note: Dose delivery by method/modality other than these must be equivalent. * No harm in changing current asthma therapy to investigator, subject (legal representation, if applicable) must be willing to discontinue his/her ICS or ICS/LABA combination prior to initiating MF MDI run-in medication at Screening Visit, & transferred to open-label treatment with MF MDI 100 mcg BID for 2-3 weeks prior to Baseline Visit. * To document diagnosis of asthma & assure responsiveness to bronchodilators before randomization 1 of these can be used at Screening Visit or thereafter, but prior to Baseline Visit: Demonstrate increase in absolute FEV1 \>=12% & \>=200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose 360-400 mcg) or nebulized short-acting beta agonist (SABA) (2.5 mg) if confirmed as standard office practice, OR Demonstrate peak expiratory flow (PEF) variability \>20% expressed as percentage of the mean highest & lowest morning prebronchodilator (before taking albuterol/salbutamol) PEF over \>=1 week, OR Demonstrate diurnal variation in PEF of \>20% based on difference between prebronchodilator (before taking albuterol/salbutamol) morning value & postbronchodilator value (after taking albuterol/salbutamol) from evening before, expressed as percentage of mean daily PEF value. * At Screening Visit, FEV1 must be \>=60% & \<=90% predicted. * At Baseline Visit, FEV1 must be \>=60% & \<=85% predicted when all restricted drugs have been withheld for appropriate intervals. * Lab tests at Screening Visit must be normal or acceptable to investigator/sponsor and include serum pregnancy for females of child-bearing potential). Electrocardiogram (ECG) at Screening Visit, using centralized trans-telephonic technology must be acceptable to investigator. Chest x-ray performed at Screening Visit or within 12 months prior to Screening Visit must be acceptable to investigator. * Subject (legal representation, if applicable) must be willing to give written informed consent & able to adhere to schedules. * A non-pregnant woman of childbearing potential must use birth control. Includes: hormonal contraceptives including hormonal vaginal ring, hormonal implant or depot-injectable; Intrauterine device (IUD); medically prescribed topically-applied transdermal contraceptive patch; condom in combination with spermicide; monogamous relationship with male who had vasectomy. Started birth control method \>=3 months prior to Screening (exception condom), & must agree to continue its use. Female of childbearing potential who is not currently sexually active must agree & consent to using birth control, should she become active. Women who have been surgically sterilized or are \>=1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.
Exclusion criteria
* Increase/decrease in absolute FEV1 of \>20% at any time from Screening Visit up to & including Baseline Visit. Pulmonary function tests (PFTs) will be performed in the morning. * \>8 inhalations/day of SABA MDI or \>=2 nebulized treatments/day of 2.5 mg SABA on 2 consecutive days from Screening Visit up to & including Baseline Visit. * Decrease in AM/PM PEF below Screening Period stability limit on 2 consecutive days prior to randomization. * Asthma deterioration results in emergency treatment, hospitalization, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA) as judged by investigator at any time from Screening Visit up to & including Baseline Visit. * Treated in emergency room (ER) (for severe asthma exacerbation requiring systemic glucocorticosteroid treatment) or admitted to hospital for management of airway obstruction within last 3 months. * Ever required ventilator support for respiratory failure secondary to asthma. * Upper/lower respiratory tract infection within previous 2 weeks prior to Screening & Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution. * Smoker or ex-smoker & has smoked within previous year or has cumulative smoking history \>10 pack-years. * Significant abnormal vital sign. * Evidence upon visual inspection of significant oropharyngeal candidiasis at Baseline or earlier with or without treatment. If there is evidence at Screening or Pre-Baseline Visit, may be treated as appropriate & Baseline Visit can be scheduled upon resolution. * History of significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other which, in judgment of investigator, could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) insulin-dependent diabetes, hypertension being treated with beta-blockers, active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB \[Fridericia or Bazett corrections, respectively \>500 msecs), stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts (including prior cataract surgery), acquired immune deficiency syndrome (AIDS), or conditions that may interfere with respiratory function such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis. Others which are well-controlled & stable (eg hypertension not requiring beta-blockers) will not prohibit participation if deemed appropriate by investigator. * Allergic/intolerant of glucocorticoids, beta-2-agonists, or any inactive excipients in study drugs. * Female who is breast-feeding, pregnant, or intends to become pregnant while in study. * Illicit drug user. * Human immunodeficiency virus (HIV) positive (testing not done). * Unable to use oral MDI inhaler. * Has been taking any restricted medications prior to Screening without meeting required washout. * Cannot adhere to prohibited & permitted concomitant medications. * May not participate in same study at another site. Cannot participate in different study at any site, during same time. * Must not be randomized into study more than once. * No person directly associated with administration of study may participate. * Previously participated in trial with MF/F.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline to Week 12 | The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. The comparison was for MF/F vs MF. Standard deviation was pooled. |
| Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period | Across the 26 week treatment period | Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication. |
| Number of Participants With at Least One Severe Asthma Exacerbation at Week 26 | Week 26 | Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days and or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Baseline to Week 12 | Trough FEV1 is a measure of the end-of-dosing interval. The comparison was for MF/F vs F. Standard deviation was pooled. |
| Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Baseline to Week 26 | ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). The comparison was for MF/F vs placebo. Standard deviation was pooled. |
| AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | Baseline to Week 12 | The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. BMI is a number calculated from a person's weight and height. The higher the number, the higher the amount of fat. The comparison was for MF/F vs placebo. Standard deviation was pooled. |
| Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Baseline to Week 26 | AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). The comparison was for MF/F vs placebo. Standard deviation was pooled. |
| Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Baseline to Endpoint | Baseline is the proportion of nights of the last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0=no awakenings to 1=awakenings every night. The comparison was for MF/F vs placebo. Standard deviation was pooled. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MF/F MDI 100/10 mcg BID Mometasone Furoate/Formoterol Fumarate (MF/F) metered dose inhaler (MDI) 100/10 mcg twice daily (BID) | 182 |
| MF MDI 100 mcg BID Mometasone Furoate (MF) metered dose inhaler (MDI) 100 mcg twice daily (BID) | 188 |
| F MDI 10 mcg BID Formoterol Fumarate (F) metered dose inhaler (MDI) 10 mcg twice daily (BID) | 188 |
| Placebo BID Placebo twice daily (BID) | 188 |
| Total | 746 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative | 1 | 0 | 1 | 1 |
| Overall Study | Adverse Event | 7 | 6 | 9 | 6 |
| Overall Study | Did not meet protocol eligibility | 8 | 6 | 2 | 3 |
| Overall Study | Did not wish to continue (related) | 1 | 0 | 2 | 3 |
| Overall Study | Did not wish to continue (unrelated) | 4 | 9 | 5 | 6 |
| Overall Study | Lack of Efficacy | 4 | 13 | 29 | 42 |
| Overall Study | Lost to Follow-up | 0 | 1 | 5 | 1 |
| Overall Study | Noncompliance with the protocol | 11 | 6 | 8 | 10 |
Baseline characteristics
| Characteristic | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | F MDI 10 mcg BID | Placebo BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 16.9 | 39.4 years STANDARD_DEVIATION 16.7 | 38.5 years STANDARD_DEVIATION 15.6 | 38.1 years STANDARD_DEVIATION 17.4 | 38.3 years STANDARD_DEVIATION 16.6 |
| Sex: Female, Male Female | 99 Participants | 105 Participants | 103 Participants | 106 Participants | 413 Participants |
| Sex: Female, Male Male | 83 Participants | 83 Participants | 85 Participants | 82 Participants | 333 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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 882 | 33 / 182 | 37 / 188 | 32 / 188 | 24 / 188 |
| serious Total, serious adverse events | 2 / 882 | 4 / 182 | 5 / 188 | 1 / 188 | 1 / 188 |
Outcome results
Primary
Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1)
The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. The comparison was for MF/F vs MF. Standard deviation was pooled.
Time frame: Baseline to Week 12
Population: Efficacy analyses were based on randomized participants with Baseline and any post-baseline data (intent-to-treat principle).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 3.94 liters * hours | Standard Deviation 3.29 |
| MF/F MDI 100/10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Change from Baseline | 4.00 liters * hours | Standard Deviation 3.71 |
| MF MDI 100 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Change from Baseline | 2.53 liters * hours | Standard Deviation 3.71 |
| MF MDI 100 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.85 liters * hours | Standard Deviation 3.29 |
| F MDI 10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 4.09 liters * hours | Standard Deviation 3.29 |
| F MDI 10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Change from Baseline | 3.83 liters * hours | Standard Deviation 3.71 |
| Placebo BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.64 liters * hours | Standard Deviation 3.29 |
| Placebo BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Change from Baseline | 1.11 liters * hours | Standard Deviation 3.71 |
p-value: 0.001ANCOVA
Primary
Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period
Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication.
Time frame: Across the 26 week treatment period
Population: Medians for time-to-event outcomes are estimated for those who had events.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period | 45.5 Days | Inter-Quartile Range 101 |
| MF MDI 100 mcg BID | Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period | 54 Days | Inter-Quartile Range 98 |
| F MDI 10 mcg BID | Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period | 51.5 Days | Inter-Quartile Range 125.5 |
| Placebo BID | Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period | 27.5 Days | Inter-Quartile Range 87 |
Primary
Number of Participants With at Least One Severe Asthma Exacerbation at Week 26
Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days and or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication.
Time frame: Week 26
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MF/F MDI 100/10 mcg BID | Number of Participants With at Least One Severe Asthma Exacerbation at Week 26 | 30 participants |
| MF MDI 100 mcg BID | Number of Participants With at Least One Severe Asthma Exacerbation at Week 26 | 53 participants |
| F MDI 10 mcg BID | Number of Participants With at Least One Severe Asthma Exacerbation at Week 26 | 84 participants |
| Placebo BID | Number of Participants With at Least One Severe Asthma Exacerbation at Week 26 | 86 participants |
Secondary
AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup
The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. BMI is a number calculated from a person's weight and height. The higher the number, the higher the amount of fat. The comparison was for MF/F vs placebo. Standard deviation was pooled.
Time frame: Baseline to Week 12
Population: Efficacy analyses were based on randomized participants with Baseline and any post-baseline data (intent-to-treat principle).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | Less than 25 | 5.24 liters * hours | Standard Deviation 4.42 |
| MF/F MDI 100/10 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 30 or more | 3.35 liters * hours | Standard Deviation 3.68 |
| MF/F MDI 100/10 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 25 to less than 30 | 3.36 liters * hours | Standard Deviation 4.14 |
| MF MDI 100 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | Less than 25 | 3.19 liters * hours | Standard Deviation 4.42 |
| MF MDI 100 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 30 or more | 1.69 liters * hours | Standard Deviation 3.68 |
| MF MDI 100 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 25 to less than 30 | 3.23 liters * hours | Standard Deviation 4.14 |
| F MDI 10 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 25 to less than 30 | 4.26 liters * hours | Standard Deviation 4.14 |
| F MDI 10 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | Less than 25 | 4.34 liters * hours | Standard Deviation 4.42 |
| F MDI 10 mcg BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 30 or more | 3.13 liters * hours | Standard Deviation 3.68 |
| Placebo BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | Less than 25 | 2.22 liters * hours | Standard Deviation 4.42 |
| Placebo BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 30 or more | -0.73 liters * hours | Standard Deviation 3.68 |
| Placebo BID | AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup | 25 to less than 30 | 1.22 liters * hours | Standard Deviation 4.14 |
p-value: 0.015ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12
Trough FEV1 is a measure of the end-of-dosing interval. The comparison was for MF/F vs F. Standard deviation was pooled.
Time frame: Baseline to Week 12
Population: Efficacy analyses were based on randomized participants with Baseline and any post-baseline data (intent-to-treat principle).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Baseline | 2.50 liters | Standard Deviation 2.56 |
| MF/F MDI 100/10 mcg BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Change from Baseline | 0.18 liters | Standard Deviation 0.21 |
| MF MDI 100 mcg BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Change from Baseline | 0.16 liters | Standard Deviation 0.21 |
| MF MDI 100 mcg BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Baseline | 2.41 liters | Standard Deviation 2.46 |
| F MDI 10 mcg BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Baseline | 2.47 liters | Standard Deviation 2.52 |
| F MDI 10 mcg BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Change from Baseline | 0.11 liters | Standard Deviation 0.21 |
| Placebo BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Baseline | 2.46 liters | Standard Deviation 2.5 |
| Placebo BID | Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 | Change from Baseline | 0.04 liters | Standard Deviation 0.21 |
p-value: 0.073Longitudinal Model
Secondary
Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA)
Baseline is the proportion of nights of the last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0=no awakenings to 1=awakenings every night. The comparison was for MF/F vs placebo. Standard deviation was pooled.
Time frame: Baseline to Endpoint
Population: Efficacy analyses were based on randomized participants with Baseline and any post-baseline data (intent-to-treat principle).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Baseline | 0.13 Proportion of Nights | Standard Deviation 0.12 |
| MF/F MDI 100/10 mcg BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Change from Baseline | -0.06 Proportion of Nights | Standard Deviation 0.16 |
| MF MDI 100 mcg BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Change from Baseline | -0.03 Proportion of Nights | Standard Deviation 0.16 |
| MF MDI 100 mcg BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Baseline | 0.12 Proportion of Nights | Standard Deviation 0.12 |
| F MDI 10 mcg BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Change from Baseline | -0.03 Proportion of Nights | Standard Deviation 0.16 |
| F MDI 10 mcg BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Baseline | 0.15 Proportion of Nights | Standard Deviation 0.15 |
| Placebo BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Change from Baseline | 0.02 Proportion of Nights | Standard Deviation 0.16 |
| Placebo BID | Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA) | Baseline | 0.13 Proportion of Nights | Standard Deviation 0.14 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score
AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). The comparison was for MF/F vs placebo. Standard deviation was pooled.
Time frame: Baseline to Week 26
Population: Efficacy analyses were based on randomized participants with Baseline and any post-baseline data (intent-to-treat principle).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Baseline | 5.60 units on a scale | Standard Deviation 0.93 |
| MF/F MDI 100/10 mcg BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Change from Baseline | 0.44 units on a scale | Standard Deviation 0.73 |
| MF MDI 100 mcg BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Change from Baseline | 0.39 units on a scale | Standard Deviation 0.73 |
| MF MDI 100 mcg BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Baseline | 5.65 units on a scale | Standard Deviation 1 |
| F MDI 10 mcg BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Baseline | 5.60 units on a scale | Standard Deviation 0.98 |
| F MDI 10 mcg BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Change from Baseline | 0.15 units on a scale | Standard Deviation 0.73 |
| Placebo BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Baseline | 5.76 units on a scale | Standard Deviation 1.02 |
| Placebo BID | Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score | Change from Baseline | 0.06 units on a scale | Standard Deviation 0.73 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score
ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). The comparison was for MF/F vs placebo. Standard deviation was pooled.
Time frame: Baseline to Week 26
Population: Efficacy analyses were based on randomized participants with Baseline and any post-baseline data (intent-to-treat principle).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Baseline | 1.34 units on a scale | Standard Deviation 0.71 |
| MF/F MDI 100/10 mcg BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Change from Baseline | -0.40 units on a scale | Standard Deviation 0.65 |
| MF MDI 100 mcg BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Change from Baseline | -0.32 units on a scale | Standard Deviation 0.65 |
| MF MDI 100 mcg BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Baseline | 1.29 units on a scale | Standard Deviation 0.6 |
| F MDI 10 mcg BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Baseline | 1.38 units on a scale | Standard Deviation 0.76 |
| F MDI 10 mcg BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Change from Baseline | -0.12 units on a scale | Standard Deviation 0.65 |
| Placebo BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Baseline | 1.23 units on a scale | Standard Deviation 0.71 |
| Placebo BID | Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score | Change from Baseline | -0.11 units on a scale | Standard Deviation 0.65 |
p-value: 0.001ANCOVA