A 12-Week Efficacy and Safety Study of Two Doses of Mometasone Furoate/Formoterol Combination Formulation Compared With Mometasone Furoate Monotherapy, in Persistent Asthmatics Previously Treated With High-Dose Inhaled Glucocorticosteroids
Overview
- Phase
- Phase 3
- Intervention
- Mometasone furoate/formoterol (MF/F) combination
- Conditions
- Asthma
- Sponsor
- Organon and Co
- Enrollment
- 834
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a randomized, multicenter, double blind, parallel-group study evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 400/10 mcg twice daily (BID) compared with MF MDI 400 mcg BID for 12 weeks. Prior to the 12-week double-blind treatment period, subjects will receive open-label MF MDI 400 mcg 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 hr) of the change from Baseline to the Week 12 Endpoint in forced expiratory volume in one second (FEV1).
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject must be at least 12 years of age, of either sex, and of any race, with a diagnosis of asthma of at least 12 months duration that is consistent with the following definition:
- •The diagnosis of asthma is based upon clinical history and examination, pulmonary function parameters, and response to beta2-agonists, according to international guidelines.
- •A subject must have been using a high dose of inhaled glucocorticosteroid (ICS) either alone or in combination with a long-acting beta2 agonist (LABA) for at least 12 weeks prior to Screening, with no use of oral glucocorticosteroids within 30 days prior to Screening. A subject must have been on a stable asthma regimen (daily dose unchanged) for at least 2 weeks prior to Screening. High daily doses of ICS are defined as follows:
- •\>1000 mcg beclomethasone chlorofluorocarbon (CFC)
- •\>500 mcg beclomethasone hydrofluoroalkane (HFA)
- •\>1000 mcg budesonide dry powder inhaler (DPI)
- •\>2000 mcg flunisolide
- •\>500 mcg fluticasone
- •\>400 mcg MF
- •\>2000 mcg triamcinolone acetonide
Exclusion Criteria
- •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. Pulmonary function tests (PFTs) will be performed in the morning.
- •A subject who requires the use of \>8 inhalations per day of short-acting beta agonists (SABA) MDI or \>=2 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 peak expiratory flow (PEF) below the Run-in Period stability limit on any 2 consecutive days prior to randomization.
- •A subject who experiences a clinical asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication \[including oral or other systemic corticosteroids, but allowing SABAs\]), at any time from the Screening Visit up to and including the Baseline Visit.
- •A subject who has been treated in the emergency room (for a severe asthma exacerbation), or admitted to the hospital for management of airway obstruction, within the last 3 months.
- •A subject who has ever required ventilator support for respiratory failure secondary to asthma.
- •A subject who has experienced an upper or lower respiratory tract infection (viral or bacterial) within the previous 2 weeks prior to Screening and Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution of the event to re-assess eligibility.
- •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.
- •A subject with a clinically significant abnormal vital sign.
- •A subject with evidence (upon visual inspection, laboratory culture is not required) of clinically significant oropharyngeal candidiasis at Baseline (Visit 3) with or without treatment. If there is evidence of oropharyngeal candidiasis at Screening or Pre-Baseline Visit, the subject may be treated as appropriate and the Baseline Visit can be scheduled upon resolution. If there is evidence of oropharyngeal candidiasis at the Baseline Visit, the subject may be treated as appropriate and the visit can be rescheduled upon resolution.
Arms & Interventions
MF/F MDI 400/10 mcg BID
Mometasone Furoate 400 mcg and formoterol 10 mcg fixed dose combination taken twice daily Participants received 2 to 3 weeks (approximately) of open-label, run-in medication with MF MDI 400 mcg BID prior to the 12-week double-blind treatment period
Intervention: Mometasone furoate/formoterol (MF/F) combination
MF/F MDI 200/10 mcg BID
Mometasone Furoate 200 mcg and formoterol 10 mcg fixed dose combination taken twice daily Participants received 2 to 3 weeks (approximately) of open-label, run-in medication with MF MDI 400 mcg BID prior to the 12-week double-blind treatment period
Intervention: Mometasone furoate/formoterol (MF/F) combination
MF MDI 400 mcg BID
Mometasone Furoate 400 mcg taken twice daily Participants received 2 to 3 weeks (approximately) of open-label, run-in medication with MF MDI 400 mcg BID prior to the 12-week double-blind treatment period
Intervention: Mometasone furoate MDI (MF MDI)
Outcomes
Primary Outcomes
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)
Time Frame: 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 versus MF. Standard deviation was pooled.
Secondary Outcomes
- Change From Baseline to Week 12 in Asthma Control Questionnaire (ACQ) Total Score(Baseline to Week 12)
- Change From Baseline to Week 12 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score(Baseline to Week 12)
- Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma That Require Use of Short-Acting Beta Agonists (SABA)(12-week Treatment Period)