Official Title: “A 52-Week Efficacy and Safety Non-Inferiority Study of Fluticasone Propionate/Salmeterol 250/50mcg BID Delivered by Dry Powder Inhaler (Diskus) Versus Mometasone Furoate/Formoterol Fumarate 200/10mcg BID Delivered by Pressurized Metered-Dose Inhaler in Persistent Asthmatics Previously Treated With Medium Doses of Inhaled Glucocorticosteroids”

This study is being conducted to demonstrate the non-inferiority between two inhaled glucocorticosteroids and long-acting bronchodilator combination drugs called mometasone furoate/formoterol fumarate in a metered-dose inhaler (MDI) and fluticasone propionate/salmeterol in a dry powder inhaler (DPI) on lung function. Information on the onset of action, the overall safety, and how the drugs control asthma will also be assessed.

The study is approximately 1 year in duration.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind (Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

Intervention(s) in this Clinical Trial

• Drug: Mometasone furoate/formoterol (MF/F) combination
  • MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks.
• Drug: Fluticasone propionate and salmeterol (F/SC) DPI
  • Fluticasone propionate 250 mcg and salmeterol 50 mcg fixed dose combination dry powder inhaler taken twice daily for 52 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: MF/F MDI 200/10 mcg BID
  • Mometasone furoate 200 mcg and formoterol 10 mcg fixed dose combination taken twice daily.
• Active Comparator: F/SC DPI 250/50 mcg BID
  • Fluticasone propionate/salmeterol (F/SC) 250/50 mcg BID

Primary Measures

• The AUC(0-12 hr) of the change from Baseline to Week 12 in FEV1.
  • Time Frame: Baseline to Week 12
    Safety Issue?: No

Secondary Measures

• Onset-of-action based on change from Baseline FEV1 at the 5 min PFT assessment on Day 1.
  • Time Frame: Baseline to Week 52
    Safety Issue?: No
• Change from Baseline in Asthma Control Questionnaire total score over the 52-week Treatment Period.
  • Time Frame: Baseline to Week 52
    Safety Issue?: No
• Time-to-first asthma exacerbation over the 52-week Treatment Period.
  • Time Frame: Baseline to Week 52
    Safety Issue?: No
• The proportion of symptom-free days and nights (combined) over the 52-week Treatment Period.
  • Time Frame: Baseline to Week 52
    Safety Issue?: No

Inclusion Criteria:

• Subjects must have a diagnosis of asthma for at least 12 months' duration.
• A subject must have been using a medium daily dose of inhaled glucocorticosteroids (alone or in combination with LABA) for at least 12 weeks and must have been on a stable regimen for at least 2 weeks prior to Screening.
• If there is no inherent harm in changing the subject's current asthma therapy, the subject must be willing to discontinue his/her prescribed ICS or ICS/LABA prior to initiating MF MDO run-in medication.
• The diagnosis of asthma must be documented by either demonstrating an increase in absolute forced expiratory volume in 1 second (FEV1) of at least 12% and a volume increase of at least 200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol or of nebulized SABA OR PEF variability of more than 20% OR a diurnal variation PEF of more than 20% based on the difference between pre-bronchodilator (before taking albuterol/salbutamol) morning value and the post-bronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value on any day during the open-label
• Run-in Period.
• A subject must have a history of >= 2 asthma-related unscheduled visits to a physician or to an emergency room within the past year AND >= 3 asthma-related unscheduled visits within the past 2 years.
• Prior to randomization subjects must have used a total of 12 or more inhalations of SABA rescue medication during the last 10 days of run-in.
• Clinical laboratory tests (complete blood counts [CBC], blood chemistries, including serum pregnancy for females of child-bearing potential, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor before the subject is instructed to start using open-label MF MDI run-in medication.
• An electrocardiogram (ECG) performed at the Screening Visit, using a centralized trans-telephonic technology, must be clinically acceptable to the investigator.
• A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator.
• A non-pregnant female subject of childbearing potential must be using a medically acceptable, adequate form of birth control. A female subject of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment.

Exclusion Criteria:

• A subject who demonstrates a change in absolute FEV1 of > 20% at any time between the Screening and Baseline Visits on any 2 consecutive days between the Screening and Baseline visits.
• A subject who requires the use of greater than 8 inhalations per day of SABA MDI or 2 or more nebulized treatments per day of 2.5 mg SABA on any 2 consecutive days between the Screening and Baseline Visits.
• A subject who experiences a decrease in AM or PM PEF below the Run-in Period stability limit on any 2 consecutive days prior to randomization. The average AM and average PM
• PEF respective values from the preceding 7 days are added, divided by the number of non-missing values, and multiplied by 0.70 to determine the stability limit.
• A subject who experiences a clinical asthma exacerbation: defined as a clinical deterioration of asthma as judged by the clinical investigator between the Screening and Baseline Visits, that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Hendrik Nolte, MD, PhD Study Director Allergy/Respiratory Diseases/Clinical Immunology, Schering-Plough  

Overall Contact: SP Clinical Trial Registry Call Center 1-888-772-8734 

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00424008

Study ID Number: P04705

ClinicalTrials.gov Identifier: NCT00424008

Health Authority: United States: Food and Drug Administration