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

NCT00394355 | Completed Phase 4 Results

• 3 other identifiers: P03418Doc ID: 3387777;EUDRACT No: 2004-002930-21;
• Study Type: interventional
• Target: 566
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Mean Percent Change in the Left Total Femur From the Averaged Baseline Value to the Averaged Value at the Endpoint of Treatment Time Point

  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

  Baseline and up to ~ one year of treatment

• Summary of Change From Baseline to Endpoint in FEV1 (Forced Expiratory Volume in One Second).

  Baseline and up to ~ one year of treatment

Study Arms (4)

Group 1

EXPERIMENTAL

MF DPI 400 mcg once a day (QD) in the evening (PM)

Drug: mometasone furoate dry powder inhaler

Group 2

EXPERIMENTAL

MF DPI 200 mcg QD PM

Drug: mometasone furoate dry powder inhaler

Group 3

ACTIVE COMPARATOR

Fluticasone propionate (FP) metered dose inhaler (MDI) 250 mcg twice a day (BID)

Drug: fluticasone propionate hydrofluoroalkane (HFA)

Group 4

ACTIVE COMPARATOR

ML 10 mg QD PM

Drug: montelukast

Interventions

mometasone furoate dry powder inhaler DRUG

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.

Also known as: Asmanex

Group 1

fluticasone propionate hydrofluoroalkane (HFA) DRUG

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

Also known as: Flovent HFA

Group 3

montelukast DRUG

10 mg given once daily in the evening by mouth for 1 year.

Also known as: Singulair

Group 4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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).

You may not qualify if:

• \>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.

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Maspero J, Backer V, Yao R, Staudinger H, Teper A. Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma. J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):649-55.e1. doi: 10.1016/j.jaip.2013.07.011. Epub 2013 Oct 8.

  PMID: 24565713 RESULT

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; Fluticasone; montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Androstadienes; Androstenes; Androstanes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2006
• First Posted: November 1, 2006
• Study Start: September 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: May 22, 2024
• Results First Posted: March 7, 2011

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share