Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04073AM1)(COMPLETED)
Condition: Asthma
MeSH terms: Asthma
Intervention: Mometasone Furoate/Formoterol Fumarate Combination MDI 100/10 mcg BID; Mometasone Furoate MDI (MF MDI); Formoterol Fumarate 10 mcg; Placebo
Intervention description: 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; Placebo metered dose inhaler twice a day for 26 weeks
Intervention MeSH terms: Mometasone Furoate; Formoterol Fumarate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 746.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.