Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04334AM1)(COMPLETED)

Study Overview
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Brief Summary
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This is a randomized, multi-center, double-blind, double-dummy, placebo-controlled, parallel-group study, evaluating the efficacy of mometasone furoate (MF) /formoterol fumarate (F)[MF/F] metered dose inhaler (MDI) versus MF for 26 weeks. Prior to the 26-week double-blind Treatment Period, subjects will receive open-label MF MDI 200 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) [Time Frame: Baseline to Week 12] and Time-to-First Severe Asthma Exacerbation across the 26-week treatment period.

Official Title
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A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Medium-Dose Inhaled Glucocorticosteroids

Conditions
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Asthma

Intervention / Treatment
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* Drug: mometasone furoate/formoterol fumarate combination MDI 200/10 mcg BID
* Drug: Mometasone furoate MDI (MF MDI) 200 mcg
* Drug: formoterol fumarate 10 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Adult and adolescent subjects of either sex and any race, at least 12 years of age or older, with a diagnosis of asthma of at least 12 months' duration, will be eligible for enrollment. Subjects must meet all of the inclusion criteria and none of the exclusion criteria to receive treatment assignment. Key Inclusion Criteria Include - A subject must have been using a medium daily dose of inhaled glucocorticosteroid (ICS) (either alone or in combination with a long-acting beta agonist (LABA)) for at least 12 weeks and must have been on a stable regimen (daily dose unchanged) for at least 2 weeks prior to Screening. Medium daily doses of ICS are defined as follows: >500 to 1000 mcg beclomethasone chlorofluorocarbon (CFC) >250 to 500 mcg beclomethasone hydrofluoroalkane (HFA) >600 to 1000 mcg budesonide dry powder inhaler (DPI) >1000 to 2000 mcg flunisolide >250 to 500 mcg fluticasone 400 mcg MF >1000 to 2000 mcg triamcinolone acetonide Note: Dose delivery by method or modality other than those noted above must be equivalent. If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject's current asthma therapy, then the subject (and parent/guardian, if applicable) must be willing to discontinue his/her prescribed ICS or ICS/LABA combination at the Screening Visit, and be transferred to open-label treatment with MF MDI 200 mcg BID for 2 to 3 weeks prior to the Baseline/Randomization Visit. To document the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization one of the following methods can be used at the Screening Visit, Day -14, or thereafter, but prior to the Baseline Visit: The subject must demonstrate an increase in absolute FEV1 of at least 12% and at least 200 mL within 15 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg) or of nebulized SABA (2.5 mg) if confirmed as standard office practice, OR The subject must demonstrate a peak expiratory flow (PEF) variability of more than 20% expressed as a percentage of the highest and lowest morning prebronchodilator PEF over at least 1 week, OR The subject must demonstrate a diurnal variation in PEF of more than 20% based on the difference between the prebronchodilator morning value and the postbronchodilator value from the evening before, expressed as a percentage of the mean daily PEF value. At the Screening Visit, the subject's FEV1 must be ≥60% and ≤90% predicted. At the Baseline Visit, the subject's FEV1 must be ≥60% and ≤85% predicted when all restricted medications have been withheld for the appropriate intervals. Clinical laboratory tests (complete blood counts [CBC], blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor. An electrocardiogram (ECG) using a centralized trans-telephonic technology at the Screening Visit must be clinically acceptable to the investigator. A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator. A female subject of childbearing potential must have been using a medically acceptable, adequate form of birth control. This includes: 1) hormonal contraceptives as prescribed by a physician (oral combined, hormonal implant); 2) medically prescribed intra-uterine device (IUD); 3) condom in combination with a spermicide (double barrier method); 4) monogamous relationship with a male partner who has had a vasectomy. The subject must have started this birth control method at least 3 months prior to Screening (with the exception of condom in combination with spermicide), and must agree to continue its use for the duration of the study. A female subject of childbearing potential who is not currently sexually active must agree and consent to using a medically acceptable birth control method should she become sexually active during the course of this study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A female subject of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment. Key Exclusion Criteria Include A subject who demonstrates a change (increase or decrease) in absolute FEV1 of >20% at any time from the Screening Visit up to and including the Baseline Visit. A subject who requires the use of greater than eight inhalations per day of SABA MDI, or two or more nebulized treatments per day of 2.5 mg SABA, on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit. A subject who experiences a decrease in AM or PM PEF below the Screening Period stability limit on any 2 consecutive days prior to Randomization. A subject who experiences an occurrence of any clinical deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) as judged by the clinical investigator at any time from the Screening Visit up to and including the Baseline Visit. A subject who is a smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history >10 pack-years

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MF/F MDI 200/10 mcg BID<br> | Drug: mometasone furoate/formoterol fumarate combination MDI 200/10 mcg BID<br>* MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks<br>* Other names: SCH 418131;|
| Experimental: MF MDI 200 mcg BID<br> | Drug: Mometasone furoate MDI (MF MDI) 200 mcg<br>* MF 200 mcg via metered dose inhaler twice daily for 26 weeks<br>* Other names: SCH 32088;|
| Experimental: F MDI 10 mcg BID<br> | Drug: formoterol fumarate 10 mcg<br>* F via metered dose inhaler 10 mcg twice a day for 26 weeks<br>* Other names: Foradil;|
| Placebo Comparator: Placebo BID<br> | Drug: Placebo<br>* Placebo metered dose inhaler twice a day for 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) for MF/F Versus MF |  | Baseline to Endpoint (12 weeks) | 
| Time-to-first Asthma Exacerbation Over the 26-week Treatment Period for the Comparison of MF/F Versus F | This endpoint was to measure the time it took for 50% of subjects in a treatment arm to experience a severe asthma exacerbation (also see the posted Other Pre-specified Outcome: Number of Participants With at Least One Severe Asthma Exacerbation) | 26-week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score | AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). Standard deviations are pooled. | Baseline to Week 26 | 
| Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Score | ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). | Baseline to week 26 | 
| Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta 2-agonist (SABA) | Baseline is the proportion of nights of 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. Standard deviation is pooled. | Baseline to Endpoint |