This is a 2-week double-blind, placebo-controlled, parallel group study comparing the
anti-inflammatory effects of low, medium, and high dose mometasone furoate/formoterol
fumarate (MF/F) metered dose inhaler (MDI) formulation and medium dose mometasone furoate
(MF) dry powder inhaler (DPI) and MDI formulations in adults and adolescents with persistent
allergic asthma.
Inclusion Criteria:
- To document asthma diagnosis, historical reversibility defined as an increase in
absolute forced expiratory volume (in liters) in 1 second (FEV1) of >= 12% and >= 200
mL must have been performed within 12 months of Screening. For subjects without
historical reversibility, one of the following methods can be used at the Screening
Visit or at any time before the Baseline Visit:
- Demonstration of an increase in absolute FEV1 of at least 12% and a volume
increase of at least 200 mL within 15-20 minutes after administration of 4
inhalations of albuterol/salbutamol (total dose 360 to 400 mcg) or of nebulized
short-acting beta agonist (SABA) (2. 5 mg), if confirmed as standard office
practice, OR
- Demonstration of a peak expiratory flow (PEF) variability of more than 20%
expressed as a percentage of the mean highest and lowest morning
prebronchodilator PEF over at least 1 week, OR
- Demonstration of a diurnal variation PEF of more than 20% based on the
difference between the prebronchodilator (before taking albuterol/salbutamol)
morning value and the postbronchodilator value (after taking
albuterol/salbutamol) from the evening before, expressed as a percentage of the
mean daily PEF value on any day during the open-label Run-in Period. {The
calculation formula: Diurnal PEF Variation = Absolute [(highest of 3 readings,
PM Post-bronchodilator (BD) PEF from prior evening) - (highest of 3 readings, AM
Pre-BD from morning value)]/[(highest PM Post-BD + highest AM Pre-BD)/2] * 100}
- At Screening and Baseline Visits, a subject must have persistent allergic asthma with
an FEV1 >65% predicted.
- A subject must be allergic to at least one common allergen (grasses, trees, weeds,
house dust mites, molds, dog and cat) as demonstrated by clinical symptoms when
exposed to the allergen(s), and by skin prick testing or a radioallergosorbent (RAST)
class >1 (excluding modified RAST procedure [mRAST]) within 2 years of inclusion in
the study.
- If, based upon the medical judgment of the investigator, there is no inherent harm in
changing the subject's current asthma therapy, the subject and/or parent/guardian)
must agree to discontinue prescribed inhaled corticosteroid (ICS), anticholinergics,
leukotriene receptor inhibitors, and long-acting beta-2 agonists at the Screening
Visit as per required washouts, and be transferred to treatment with SABA for relief
for 2 weeks before the Baseline/Randomization Visit.
- Clinical laboratory tests (complete blood count, blood chemistries, and urinalysis)
conducted at the Screening Visit must be within normal limits or clinically
acceptable to the investigator.
- An electrocardiogram (ECG) performed at the Screening Visit or within 30 days prior
to Screening Visit must be clinically acceptable to the investigator and have a QTc
interval <440 milliseconds for males and <450 msec for females.
- At Screening or any time prior to Baseline, a subject must have an eNO level of >30
parts per billion (ppb) at a flow rate of 50 mL/second.
- At Screening or any time before Baseline, a subject must have a sputum eosinophil
count >3% of total cell count.
- Willingness to give written informed consent and ability to adhere to dose and visit
schedules. A subject 12 to 17 years of age must also provide written assent.
- A nonpregnant female subject of childbearing potential (with a negative serum
pregnancy test at Screening) must use a medically acceptable, adequate form of birth
control. If not currently sexually active she must agree to use a double-barrier
method if she becomes sexually active during the study.
Exclusion Criteria:
- Use of systemic glucocorticosteroids within 3 months before Screening.
- Upper or lower respiratory tract infection within 4 weeks before Screening.
- Decrease in absolute FEV1 >20% between Screening and Baseline Visits.
- Requirement for > 8 inhalations per day of SABA MDI, or 2 or more nebulized
treatments of 2. 5 mg SABA, on any 2 consecutive days between the Screening and
Baseline Visits.
- A decrease in AM or PM PEF below the Run-in Period stability limit on any 2
consecutive days before Baseline. At Visit 1, the Run-in Period stability limit for
PEF will be established based on the subject's personal best. If the subject does not
have a historical personal best, the historical PEF measurement will be the PEF
predicted based on the subject's sex, age, and height. PEF value to be multiplied by
0. 70 to determine stability limit.
- A clinical asthma exacerbation defined as a clinical deterioration of asthma that
results in emergency treatment, hospitalization for asthma, or treatment with
additional, excluded asthma medication (including oral or other systemic
corticosteroids but allowing SABA), as per investigator, between Screening and
Baseline Visits.
- Inability to induce sputum after 1 or 2 trys.
