Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04431AM2)(COMPLETED)
Condition: Asthma
MeSH terms: Asthma
Intervention: Mometasone furoate/formoterol (MF/F) combination; Mometasone furoate/formoterol (MF/F) combination; Mometasone furoate MDI (MF MDI)
Intervention description: MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 12 weeks; MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 12 weeks; MF 400 mcg via metered dose inhaler twice daily for 12 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: 834.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

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).
    

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

               -  >320 mcg ciclesonide

        Note: Dose delivery by method or modality other than those noted above must be equivalent.

          -  A subject must have experienced at least one severe exacerbation requiring a course of
             oral glucocorticosteroid 2 to 12 months prior to Screening.

          -  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 prior
             to initiating MF MDI run-in medication.

          -  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 approximately 15 to 20 minutes after administration of four
                  inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg).

               -  The subject must demonstrate a peak expiratory flow (PEF) variability of more
                  than 20% expressed as a percent of the best and lowest morning pre-bronchodilator
                  PEF over at least 1 week.

               -  The subject must demonstrate a diurnal variation in 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. Note: If a subject is to qualify using diurnal variation,
                  the subject should be instructed to perform his/her PEF evaluation after using
                  his/her bronchodilator in the evening.

          -  At the Screening Visit, the subject's FEV1 must be >=50% predicted when all restricted
             medications have been withheld for the appropriate intervals.

          -  At the Baseline Visit, the subject's FEV1 must be >=50% and <=85% predicted when all
             restricted medications have been withheld for the appropriate intervals.

          -  The subject (and parent/guardian for a subject under the age of legal consent) must be
             willing to give written informed consent and be able to adhere to dose and visit
             schedules.

          -  A female subject of childbearing potential must be using a medically acceptable,
             adequate form of birth control. This includes:

               -  hormonal contraceptive as prescribed by a physician (oral combined, hormonal
                  vaginal ring, hormonal implant or depot-injectable);

               -  medically prescribed intra-uterine device (IUD);

               -  medically prescribed topically-applied transdermal contraceptive patch;

               -  condom in combination with a spermicide (double-barrier method);

               -  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 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 the open-label MF MDI Run-in
                  Period.

        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.

          -  A subject with a history of clinically significant renal, hepatic, cardiovascular,
             metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal,
             cerebrovascular, or other significant medical illness or disorder which, in the
             judgment of the investigator, could interfere with the study, or require treatment
             that might interfere with the study. Specific examples include (but are not limited
             to) insulin-dependent diabetes, hypertension being treated with beta blockers, active
             hepatitis, coronary artery disease, arrhythmia, stroke, severe rheumatoid arthritis,
             chronic open-angle glaucoma or posterior subcapsular cataracts, acquired immune
             deficiency syndrome (AIDS), or conditions that may interfere with respiratory function
             such as clinically diagnosed chronic obstructive pulmonary disease (COPD), chronic
             bronchitis, emphysema, bronchiectasis, cystic fibrosis, etc. Other conditions that are
             well-controlled and stable (eg, hypertension not requiring beta blockers) will not
             prohibit participation if deemed appropriate per the investigator's judgment.

          -  A subject who is known to be allergic to or intolerant of ICS, beta2 agonists, or any
             of the excipients present in the medications used in this study.

          -  A female subject who is breast-feeding, pregnant, or intends to become pregnant while
             participating in this study.

          -  A subject who is a known illicit drug user.

          -  A subject who is known to be human immunodeficiency virus (HIV) positive (HIV testing
             will not be conducted in this study).

          -  A subject who is unable to correctly use an oral MDI inhaler.

          -  A subject who has been taking any of the restricted medications prior to Screening
             without meeting the required washout timeframes.

          -  A subject who cannot adhere to the permitted concomitant medications and prohibited
             medications.

          -  A subject participating in this study may not participate in this same study at
             another investigational site. In addition, a subject cannot participate in a different
             investigational study at any site, during the same timeframe of this study.

          -  A subject must not be randomized into this study more than once.

          -  No person directly associated with the administration of the study may participate as
             a study subject. No family member of the investigational study staff may participate
             in this study.

          -  A subject who previously participated in a trial with MF/F.

          -  Subjects with a history of significant QTC prolongation (ie, QTc>500 msec) are
             excluded from participation in the study.