Effects of Mometasone Furoate Dry Powder Inhaler, Fluticasone Propionate, and Montelukast on Bone Mineral Density in Asthmatics (Study P03418)
Condition: Asthma
MeSH terms: Asthma
Intervention: mometasone furoate dry powder inhaler; mometasone furoate dry powder inhaler; fluticasone propionate hydrofluoroalkane (HFA); montelukast
Intervention description: 400 mcg MF DPI via a breath-actuated, dry-powder inhaler and a placebo tablet given by mouth once daily in the evening for 1 year.; 200 mcg MF DPI via a breath-actuated, dry-powder inhaler and a placebo tablet given by mouth once daily in the evening for 1 year.; 250 mcg FP HFA given twice a day via a metered-dose inhaler and a placebo tablet given once daily in the evening for 1 year; 10 mg given once daily in the evening by mouth for 1 year.
Intervention MeSH terms: Fluticasone; Xhance; Mometasone Furoate; Montelukast
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 566.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      This is a randomized, multi-center, parallel-group, active-controlled, double-blind study
      evaluating the effects of mometasone furoate (MF) dry powder inhaler (DPI) on bone mineral
      density (BMD) in subjects with asthma. The mean percent change in lumbar spine BMD from the
      averaged baseline value (the average of the two scan results prior to treatment) to the
      endpoint of treatment time point (the average of the last two valid post-baseline scan
      results during treatment) for the comparison of MF DPI 400 mcg daily in the evening versus
      montelukast (ML) 10 mg daily in the evening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent, adhere to schedules.

          -  Inform usual treating medical doctor (MD) of study participation.

          -  Female 18 to 40, male 18 to 50, any race.

          -  >=3-month asthma history.

          -  Never treated with inhaled corticosteroids (ICS) for asthma or not have taken ICS for
             ≥3 months prior to Screening.

          -  Prebronchodilator forced expiratory volume (liters) in 1 second (FEV1) >=60% & <=90%
             predicted at both Screening & Baseline, when all restricted medications withheld.

          -  Prior to randomization, demonstrate increase in absolute FEV1 of >=12%, with absolute
             volume increase of >=200 mL, after reversibility testing.

          -  Lab tests normal/acceptable to investigator/sponsor. Electrocardiogram (ECG) performed
             at screening or <30 days of screening normal/acceptable to investigator. Chest x-ray
             performed at screening or <12 months of screening normal/acceptable to investigator.

          -  25-hydroxy vitamin D level >=15 ng/mL. If <15, re-tested after taking calcium plus
             vitamin D for 4 weeks.

          -  Free of significant disease (other than asthma) known to affect bone mineral
             metabolism including renal disease, unstable hyperthyroidism or other
             endocrinopathies, Paget's disease, osteoporosis, malabsorption, or others that could
             interfere with study evaluations (eg scoliosis, metal pins, calcification in
             spine/femur).

          -  Women of childbearing potential must use birth control. Includes: hormonal
             contraceptive, intra-uterine device (IUD); condom in combination with spermicide;
             monogamous relationship with male who had vasectomy or is using condom. Started method
             ≥3 months prior to Screening (exception condom), & agree to continue for duration.
             Women who are not currently sexually active must agree/consent to using double-barrier
             method if become active. Females must have negative serum pregnancy test at Screening.

          -  2 valid scans, as confirmed by local dual energy x-ray absorptiometry (DXA) center,
             for lumbar spine, left total femur, & femoral neck prior to randomization. Valid scans
             will be 2 scans of same region, performed on same day, that agree within 5% & scans
             are technically satisfactory (eg correct scan mode, no artifacts present, correct
             region).

        Exclusion Criteria:

          -  >12 inhalations/day of salbutamol on 2 consecutive days between Screening & Baseline.

          -  Increase/decrease in FEV1 of >=20% between Screening & Baseline.

          -  Treated with methotrexate, cyclosporin, gold, or other cytotoxic agents, for asthma or
             concurrent condition within last 3 months.

          -  Pipe/cigar smoking history.

          -  Smoker/ex-smoker who smoked within previous year or has smoking history ≥10
             pack-years.

          -  Upper/lower respiratory tract infection within 2 weeks prior to Screening & Baseline.
             Can be rescheduled.

          -  >14 days of oral steroids within previous 12 months or required burst of systemic
             steroids within previous month.

          -  Ever required ventilator support for respiratory failure secondary to asthma.

          -  Treated in emergency room (ER) for asthma exacerbation or admitted to hospital for
             management of airway obstruction on 1 occasion in last 3 months or on >=2 occasions
             within last 6 months.

          -  Chronic bronchitis, bronchiectasis, emphysema or cystic fibrosis.

          -  Participated in study within last 30 days.

          -  Allergic to/intolerant of ICS, beta-agonists, or drugs/excipients in study.

          -  Average of 2 lumbar spine (L1-L4) scans at Screening is >2 standard deviations below
             normal.

          -  Condition that might affect ability to ambulate normally, (ie major surgical
             procedure). Condition that may interfere with BMD measurement.

          -  History of renal, hepatic, cardiovascular, metabolic, neurologic, hematologic,
             respiratory, gastrointestinal, cerebrovascular, or other which could interfere with
             study or require treatment which might interfere (eg calcium urolithiasis or
             absorptive hypercalcuria, insulin dependent diabetes, cancer within last 10 years
             (except basal cell carcinoma), active hepatitis, coronary artery disease, stroke,
             rheumatoid arthritis, human immunodeficiency virus (HIV), or respiratory conditions
             such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, cystic
             fibrosis. Others which are well-controlled & stable (eg hypertension, arrhythmia,
             subjects on stable thyroid hormone replacement for at least 3 months whose thyroid
             stimulating hormone (TSH) levels are normal) may be allowed.

          -  Treated within last year with drug known to interfere with bone metabolism including:
             bisphosphonates, estrogens such as depot injectables (estrogens used in oral combined
             hormonal contraceptives are allowed if dose is stable throughout), high-dose fluoride,
             & thyroid replacement hormones (if not stabilized).

          -  History &/or presence of intraocular pressure in either eye >=22 mm Hg, glaucoma, &/or
             posterior subcapsular cataracts. History &/or presence of nuclear cataract or
             undergone bilateral lens extraction may be eligible.

          -  The subject has undergone incisional or intraocular surgery in which the natural lens
             is still present in the eye.

          -  The subject has a history of penetrating trauma to both eyes.

          -  The subject has one or more of the following lens opacities classification system
             version III (LOCS III) grades at screening: nuclear opalescence (NO) >=3.0, nuclear
             color (NC) >=3.0, cortical (C) >=2.0, posterior (P) >=0.5.

          -  Pregnant, breast-feeding, or postmenopausal women. Amenorrhea >6 months will be
             excluded (exception hysterectomy). Bilateral oophorectomy excluded.

          -  Relevant abnormal Baseline vital sign.

          -  Body mass index (BMI) >35 kg/m2.

          -  HIV positive (testing not performed).

          -  Alcoholic or illicit drug abuser.

          -  Evidence of oropharyngeal candidiasis at Baseline with or without treatment. If
             evidence at Screening, may be treated as appropriate & visit can be scheduled upon
             resolution. If evidence at Baseline Visit, may be treated as appropriate & visit can
             be rescheduled upon resolution.

          -  Normal sleep/wake cycle is inverted (eg night shift workers).

          -  Taken restricted medications prior to Screening.

          -  Cannot adhere to prohibited & permitted concomitant medications.

          -  No subject may participate in this same study at another site or simultaneously in any
             other study.

          -  No person directly associated with administration of study may participate.