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 Low-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 100 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: August 2008

Intervention(s) in this Clinical Trial

• Drug: mometasone furoate/formoterol fumarate combination MDI 100/10 mcg BID
  • MF/F 100/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks
• Drug: Mometasone furoate MDI (MF MDI)
  • MF 100 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 100/10 mcg BID
• Experimental: MF MDI 100 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 that is consistent with the following: Diagnosis based on clinical history & examination, pulmonary function parameters & response to beta-2-agonists, according to international guidelines.
• Been using low daily dose of ICS (either alone or in combination with LABA) >=12 weeks
• & been on stable asthma regimen for >=2 weeks prior to Screening. Low daily doses of

ICS are:

• 200-500 mcg beclomethasone CFC 100-250 mcg beclomethasone HFA 200-600 mcg budesonide DPI 500-1000 mcg flunisolide 100-250 mcg fluticasone 200 mcg MF 400-1000 mcg triamcinolone acetonide 80 to 160 mcg ciclesonide Note: Dose delivery by method/modality other than these must be equivalent.
• No harm in changing current asthma therapy to investigator, subject (legal representation, if applicable) must be willing to discontinue his/her ICS or ICS/LABA combination prior to initiating MF MDI run-in medication at Screening Visit, &
• transferred to open-label treatment with MF MDI 100 mcg BID for 2-3 weeks prior to Baseline Visit.
• To document diagnosis of asthma & assure responsiveness to bronchodilators before randomization 1 of these can be used at Screening Visit or thereafter, but prior to

Baseline Visit:

• Demonstrate increase in absolute FEV1 >=12% & >=200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose 360-400 mcg) or nebulized SABA (2.5 mg) if confirmed as standard office practice, OR Demonstrate
• PEF variability >20% expressed as percentage of the mean highest & lowest morning prebronchodilator (before taking albuterol/salbutamol) PEF over >=1 week, OR Demonstrate diurnal variation in PEF of >20% based on difference between prebronchodilator (before taking albuterol/salbutamol) morning value & postbronchodilator value (after taking albuterol/salbutamol) from evening before, expressed as percentage of mean daily PEF value.
• At Screening Visit, FEV1 must be >=60% & <=90% predicted.
• At Baseline Visit, FEV1 must be >=60% & <=85% predicted when all restricted drugs have been withheld for appropriate intervals.
• Lab tests at Screening Visit must be normal or acceptable to investigator/sponsor and include serum pregnancy for females of child-bearing potential). ECG at Screening Visit, using centralized trans-telephonic technology must be acceptable to investigator. Chest x-ray performed at Screening Visit or within 12 months prior to Screening Visit must be acceptable to investigator.
• Subject (legal representation, if applicable) must be willing to give written informed consent & able to adhere to schedules.
• A non-pregnant of childbearing potential must use birth control. Includes: hormonal contraceptives including hormonal vaginal ring, hormonal implant or depot-injectable;
• IUD; medically prescribed topically-applied transdermal contraceptive patch; condom in combination with spermicide; monogamous relationship with male who had vasectomy.
• Started birth control method >=3 months prior to Screening (exception condom), & must agree to continue its use. Female of childbearing potential who is not currently sexually active must agree & consent to using birth control, should she become active.
• Women who have been surgically sterilized or are >=1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.

Exclusion Criteria:

• Increase/decrease in absolute FEV1 of >20% at any time from Screening Visit up to &
• including Baseline Visit. PFTs will be performed in the morning.
• >8 inhalations/day of SABA MDI or >=2 nebulized treatments/day of 2.5 mg SABA on 2 consecutive days from Screening Visit up to& including Baseline Visit.
• Decrease in AM/PM PEF below Screening Period stability limit on 2 consecutive days prior to randomization.
• Asthma deterioration results in emergency treatment, hospitalization, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA) as judged by investigator at any time from
• Screening Visit up to & including Baseline Visit.
• Treated in ER (for severe asthma exacerbation requiring systemic glucocorticosteroid treatment) or admitted to hospital for management of airway obstruction within last 3 months.
• Ever required ventilator support for respiratory failure secondary to asthma.
• Upper/lower respiratory tract infection within previous 2 weeks prior to Screening &
• Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution.
• Smoker or ex-smoker & has smoked within previous year or has cumulative smoking history >10 pack-years.
• Significant abnormal vital sign.
• Evidence upon visual inspection of significant oropharyngeal candidiasis at Baseline or earlier with or without treatment. If there is evidence at Screening or Pre-Baseline Visit, may be treated as appropriate & Baseline Visit can be scheduled upon resolution.
• History of significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other which, in judgment of investigator, could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) insulin-dependent diabetes, hypertension being treated with beta-blockers, active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB [Fridericia or Bazett corrections, respectively >500 msecs), stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts (including prior cataract surgery), AIDS, or conditions that may interfere with respiratory function such as COPD, chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis. Others which are well-controlled & stable (eg hypertension not requiring beta-blockers) will not prohibit participation if deemed appropriate by investigator.
• Allergic/intolerant of glucocorticoids, beta-2-agonists, or any inactive excipients in study drugs.
• Female who is breast-feeding, pregnant, or intends to become pregnant while in study.
• Illicit drug user.
• HIV positive (testing not done).
• Unable to use oral MDI inhaler.
• Has been taking any restricted medications prior to Screening without meeting required washout.
• Cannot adhere to prohibited & permitted concomitant medications.
• May not participate in same study at another site. Cannot participate in different study at any site, during same time.
• Must not be randomized into study more than once.
• No person directly associated with administration of study may participate.
• 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 October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00383552

Study ID Number: P04073

ClinicalTrials.gov Identifier: NCT00383552

Health Authority: United States: Food and Drug Administration