Effects of Mometasone Furoate Dry Powder Inhaler, Fluticasone Propionate, and Montelukast on Bone Mineral Density in Asthmatics (Study P03418AM4)

Condition(s) targeted: Asthma

Intervention: mometasone furoate dry powder inhaler (Drug); mometasone furoate dry powder inhaler (Drug); fluticasone propionate HFA (Drug); montelukast (Drug); montelukast (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Schering-Plough

Official(s) and/or principal investigator(s):
Ariel Teper, MD, Study Director, Affiliation: Schering-Plough

Overall contact:
SP Clinical Trial Registry Call Center, Phone: 1-888-772-8734

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: 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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety Study

Primary outcome: Mean % change in lumbar spine BMD from the averaged baseline value (average of two scan results prior to treatment) to the endpoint of treatment time point, ie, average of last two valid post Baseline BMD scans during treatment period carried forward

Secondary outcome:

Mean percent change in the left total femur and femoral neck BMD from the averaged baseline value to the averaged value at the endpoint of treatment time point.

All BMD assessments.

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Informed consent, adhere to schedules.

- Inform usual treating MD of study participation.

- Female 18 to 40, male 18 to 50, any race.

- >=3-month asthma history.

- Never treated with ICS for asthma or not have taken ICS for ≥3 months prior to

Screening.

- Prebronchodilator 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. 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, 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 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 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, HIV, or respiratory conditions such as 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 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 LOCS III grades at screening: NO >=3. 0,

NC >=3. 0, C >=2. 0, 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.

- 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.

SP Clinical Trial Registry Call Center, Phone: 1-888-772-8734

Investigational Site 2, Buenos Aires C1425AUA, Argentina; Recruiting

Investigational Site 49, Ramos Mejia B1704ESN, Argentina; Recruiting

Investigational Site 5, Ciudad de Buenos Aires C1425DTG, Argentina; Recruiting

Investigational Site 6, BUENOS AIRES C1424BSF, Argentina; Recruiting

Investigational Site 7, CAPITAL FEDERAL 1272, Argentina; Recruiting

Investigational Site 4, Florida B1602DO, Argentina; Recruiting

Investigational Site 65, San Martin B1650CSQ, Argentina; Recruiting

Investigational Site 66, Buenos Aires C1122AAJ, Argentina; Recruiting

Investigational Site 8, Rancagua, Chile; Recruiting

Investigational Site 9, Santiago, Chile; Recruiting

Investigational Site 10, Santiago, Chile; Recruiting

Investigational Site 11, Santiago, Chile; Recruiting

Investigational Site 12, Bogota, Colombia; Recruiting

Investigational Site 16, Bogota, Colombia; Recruiting

Investigational Site 45, Bogota, Colombia; Recruiting

Investigational Site 15, Bogota 01, Colombia; Recruiting

Investigational Site 17, Bogota, Colombia; Recruiting

Investigational Site 18, Bogota, Colombia; Recruiting

Investigational Site 13, Bogota, Colombia; Recruiting

Investigational Site 50, Barranquilla, Colombia; Recruiting

Investigational Site 51, Barranquilla, Colombia; Recruiting

Investigational Site 52, Barranquilla 05, Colombia; Recruiting

Investigational Site 54, Medellin, Colombia; Recruiting

Investigational Site 56, Medellin 04, Colombia; Recruiting

Investigational Site 55, Medellin, Colombia; Recruiting

Investigational Site 40, Pardubice 530 02, Czech Republic; Recruiting

Investigational Site 38, Aalborg 9000, Denmark; Completed

Investigational Site 39, Ballerup 2750, Denmark; Recruiting

Investigational Site 37, Vejle 7100, Denmark; Completed

Investigational Site 21, Santo Domingo, Dominican Republic; Completed

Investigational Site 46, Santo Domingo, Dominican Republic; Recruiting

Investigational Site 47, Santo Domingo, Dominican Republic; Recruiting

Investigational Site 41, Tallinn 10128, Estonia; Completed

Investigational Site 23, Guatemala 01015, Guatemala; Recruiting

Investigational Site 24, Guatemala 01009, Guatemala; Recruiting

Investigational Site 25, Guatemala O1010, Guatemala; Recruiting

Investigational Site 26, Guatemala 01010, Guatemala; Recruiting

Investigational Site 63, Guatemala, Guatemala; Recruiting

Investigational Site 62, Guatemala City 01011, Guatemala; Recruiting

Investigational Site 42, Vilnius, Lithuania; Completed

Investigational Site 30, Mexico, D.F 06726, Mexico; Recruiting

Investigational Site 48, Mexico, D.F 03020, Mexico; Recruiting

Investigational Site 28, MEXICO, D.F. 14080, Mexico; Recruiting

Investigational Site 29, Mexico, D. F. 14050, Mexico; Recruiting

Investigational Site 67, Mexico, D.F. 14350, Mexico; Recruiting

Investigational Site 31, San Martin de Porres Lima 31, Peru; Active, not recruiting

Investigational Site 32, Cercado Lima 1, Peru; Active, not recruiting

Investigational Site 33, Lima, Peru; Recruiting

Investigational Site 34, Lima, Peru; Recruiting

Investigational Site 35, Jesus Maria Lima 11, Peru; Recruiting

Investigational Site 36, Lima, Peru; Recruiting

Investigational Site 44, Bucuresti 030463, Romania; Completed

Investigational Site 57, Caracas, Venezuela; Recruiting

Investigational Site 59, Caracas, Venezuela; Recruiting

Investigational Site 60, Caracas, Venezuela; Recruiting

Investigational Site 61, Caracas, Venezuela; Recruiting

Investigational Site 58, Caracas, Venezuela; Recruiting

Starting date: September 2006
Ending date: December 2009
Last updated: October 21, 2008