Official Title: “A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Medium-Dose Inhaled Glucocorticosteroids”

This is a randomized, multi-center, double-blind, double-dummy, placebo-controlled, parallel-group study, evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) versus MF for 26 weeks. Prior to the 26-week double-blind Treatment Period, subjects will receive open-label MF MDI 200 mcg twice daily (BID) for 2 to 3 weeks during the Run-in Period. Efficacy will be measured by mean change from Baseline to Week 12 in area under the forced expiratory volume in one second concentration time curve from 0 to 12 hours (FEV1 AUC[0-12 hr]).

Study Type: Interventional

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

Study Primary Completion Date: September 2008

Intervention(s) in this Clinical Trial

• Drug: mometasone furoate/formoterol fumarate combination MDI 200/10 mcg BID
  • MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks
• Drug: Mometasone furoate MDI (MF MDI)
  • MF 200 mcg via metered dose inhaler twice daily for 26 weeks
• Drug: formoterol fumarate 10 mcg
  • F via metered dose inhaler 10 mcg twice a day for 26 weeks
• Drug: Placebo
  • Placebo metered dose inhaler twice a day for 26 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: MF/F MDI 200/10 mcg BID
• Experimental: MF MDI 200 mcg BID
• Experimental: F MDI 10 mcg BID
• Placebo Comparator: Placebo BID

Primary Measures

• AUC(0-12 hr) of change from Baseline FEV1 for MF/F vs MF. Average of the 2 predose FEV1 measurements at Baseline will be subtracted from each of the serial measurements over the 12-hr. period.
  • Time Frame: AUC(0-12 hr) of change from Baseline to Week 12 FEV1 and Time to first asthma exacerbation over 26 weeks of treatment.
    Safety Issue?: No

Secondary Measures

• For MF/F vs placebo: Change from Baseline in AQLQ(S) and ACQ total score and proportion of nights across the treatment period with nocturnal awakenings due to asthma which require use of SABA.
  • Time Frame: Baseline to Week 26
    Safety Issue?: No

Inclusion Criteria:

• >=12 years, either sex, any race, asthma diagnosis >=12 months following: Diagnosis based on clinical history & examination, pulmonary parameters & response to beta-2-agonists, according to international guidelines.
• Been using medium daily dose of ICS (either alone or in combination weeks & been on stable asthma regimen for >=2 weeks prior to Screening. doses of ICS are:
• >500-1000 mcg beclomethasone CFC >250-500 mcg beclomethasone HFA budesonide DPI >1000-2000 mcg flunisolide >250-500 mcg fluticasone >400 2000 mcg triamcinolone acetonide >160 to 320 mcg ciclesonide Note: Dose delivery method/modality other than these must be equivalent.
• No harm in changing current asthma therapy to investigator, subject must be willing to discontinue his/her ICS or ICS/LABA combination initiating MF MDI run-in medication at
• Screening Visit, & transferred treatment with MF MDI 200 mcg BID for 2-3 weeks prior to Baseline
• To document diagnosis of asthma & ensure responsiveness to randomization 1 of these can be used at Screening Visit or thereafter, but Visit: Demonstrate increase in absolute FEV1 >=12% & >=200 mL approximately after administration of 4 inhalations of albuterol/salbutamol (total dose of 360 nebulized SABA (2.5 mg) if confirmed as standard office practice, OR Demonstrate variability >20% expressed as percentage of the mean highest & lowest morning prebronchodilator PEF over >=1 week, OR Demonstrate diurnal variation in on difference between prebronchodilator (before taking albuterol/salbutmaol) postbronchodilator (after taking albuterol/salbutamol) value from evening percentage of mean daily PEF value on any day during the open-label Run
• At Screening Visit, FEV1 must be >=60% & <=90% predicted.
• At Baseline Visit, FEV1 must be >=60% & <=85% predicted been withheld for appropriate intervals.
• Lab tests at Screening Visit must be normal or acceptable to serum pregnancy for females of child-bearing potential. ECG at Screening centralized trans-telephonic technology must be acceptable to investigator. performed at Screening Visit or within 12 months prior to Screening Visit acceptable to investigator.
• Subject (legal representation, if applicable) must be willing to give consent & able to adhere to schedules.
• A non-pregnant female of childbearing potential must use birth contraceptives;
• hormonal vaginal ring, hormonal implant or depot medically prescribed topically-applied transdermal contraceptive patch; combination with spermicide;
• monogamous relationship with male who Started birth control method = 3 months prior to Screening (exception agree to continue its use. Female of childbearing potential who is not currently active must agree & consent to using birth control, should she become have been surgically sterilized or are >=1 year postmenopausal are not childbearing potential. Female must have negative serum pregnancy test order to be considered eligible for the open-label MF MDI

Exclusion Criteria:

• Increase/decrease in absolute FEV1 of >20% while using ICS at any Visit up to &
• including Baseline Visit.
• >8 inhalations/day of SABA MDI or >=2 nebulized treatments/day consecutive days from
• Screening Visit up to& including Baseline Visit.
• Decrease in AM/PM PEF below Screening Period stability limit on any 2 consecutive days prior to randomization.
• Asthma deterioration results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic allowing SABA) as judged by investigator at any time from Screening including
• Baseline Visit.
• Treated in ER (for severe asthma exacerbation requiring systemic treatment) or admitted to hospital for management of airway obstruction months.
• Ever required ventilator support for respiratory failure secondary to
• Upper/lower respiratory tract infection within previous 2 weeks prior to Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution.
• Smoker or ex-smoker & has smoked within previous year or has history >10 pack-years.
• Significant abnormal vital sign.
• Evidence upon visual inspection of significant oropharyngeal earlier with or without treatment.
• History of significant renal, hepatic, cardiovascular, metabolic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgement of investigator, could interfere with study or require treatment which might study. Examples include (but are not limited to) insulin-dependentbeing treated with beta-blockers, active hepatitis, coronary artery disease, significant QTc prolongation (ie QTcF or QTcB [Fridericia or Bazett corrections, respectively >500 msecs), stroke, severe rheumatoid arthritis, or posterior subcapsular cataracts (including prior cataract surgery), AIDS, that may interfere with respiratory function such as COPD, chronic bronchiectasis, cystic fibrosis. Others which are well-controlled & stable not requiring beta-blockers) will not prohibit participation if deemed appropriate investigator.
• Allergic/intolerant of glucocorticoids, beta-2-agonists, or any drugs.
• Female who is breast-feeding, pregnant, or intends to become pregnant
• Illicit drug user.
• HIV positive (testing not done).
• Unable to use oral MDI inhaler.
• Has been taking any restricted medications prior to Screening without washout.
• Cannot adhere to prohibited & permitted concomitant medications.
• May not participate in same study at another site. In addition, a subject cannot participate in a different investigational study at any site, during the same timeframe of this study.
• Must not be randomized into study more than once.
• No person directly associated with administration of study may
• Previously participated in trial with MF/F.

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?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on August 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00383240

Study ID Number: P04334

ClinicalTrials.gov Identifier: NCT00383240

Health Authority: United States: Food and Drug Administration