Effects of Mometasone Furoate Dry Powder Inhaler, Fluticasone Propionate, and Montelukast on Bone Mineral Density in Asthmatics (Study P03418)

Study Overview
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Brief Summary
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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.

Official Title
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Comparative Study of the Effect of Two Doses of Mometasone Furoate Dry Powder Inhaler 200 mcg and 400 mcg QD PM, Fluticasone Propionate 250 mcg BID, and Montelukast 10 mg QD PM, on Bone Mineral Density in Adults With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: mometasone furoate dry powder inhaler
* Drug: mometasone furoate dry powder inhaler
* Drug: fluticasone propionate hydrofluoroalkane (HFA)
* Drug: montelukast


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>MF DPI 400 mcg once a day (QD) in the evening (PM) | Drug: mometasone furoate dry powder inhaler<br>* 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.<br>* Other names: Asmanex;|
| Experimental: Group 2<br>MF DPI 200 mcg QD PM | Drug: mometasone furoate dry powder inhaler<br>* 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.<br>* Other names: Asmanex;|
| Active Comparator: Group 3<br>Fluticasone propionate (FP) metered dose inhaler (MDI) 250 mcg twice a day (BID) | Drug: fluticasone propionate hydrofluoroalkane (HFA)<br>* 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<br>* Other names: Flovent HFA;|
| Active Comparator: Group 4<br>ML 10 mg QD PM | Drug: montelukast<br>* 10 mg given once daily in the evening by mouth for 1 year.<br>* Other names: Singulair;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in Lumbar Spine Bone Mineral Density (BMD) From the Averaged Baseline Value to the Endpoint of Treatment Time Point | The averaged baseline value is the average of the two scan results prior to treatment. The endpoint of treatment time point is the average of the last two valid post baseline BMD scans during the treatment period carried forward. | Baseline and up to   one year of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in the Left Total Femur From the Averaged Baseline Value to the Averaged Value at the Endpoint of Treatment Time Point | The averaged baseline value is the average of the two scan results prior to treatment. The endpoint of treatment time point is the average of the last two valid post baseline BMD scans during the treatment period carried forward. | Baseline and up to   one year of treatment | 
| Mean Percent Change in the Femoral Neck BMD From the Averaged Baseline Value to the Averaged Value at the Endpoint of Treatment Time Point | The averaged baseline value is the average of the two scan results prior to treatment. The endpoint of treatment time point is the average of the last two valid post baseline BMD scans during the treatment period carried forward. | Baseline and up to   one year of treatment | 
| Summary of Change From Baseline to Endpoint in FEV1 (Forced Expiratory Volume in One Second). | Mean percent change from Baseline (the last non-missing value prior to treatment) in pulmonary function test FEV1 from in-office visits and at Endpoint (last non-missing postbaseline value carried forward) | Baseline and up to   one year of treatment |