Official Title: “A 2-Week Double-Blind, Placebo-Controlled, Parallel Group Study Comparing the Anti-Inflammatory Effects of Low, Medium, and High Dose Mometasone Furoate/Formoterol Fumarate MDI Formulation and Medium Dose Mometasone Furoate DPI and MDI Formulations in Adults and Adolescents With Persistent Allergic Asthma”

This is a 2-week double-blind, placebo-controlled, parallel group study comparing the anti-inflammatory effects of low, medium, and high dose mometasone furoate/formoterol fumarate MDI formulation and medium dose mometasone furoate DPI and MDI formulations in adults and adolescents with persistent allergic asthma.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: August 2008

This is a 2-week double-blind, placebo-controlled, parallel group study comparing the anti-inflammatory effects of low, medium, and high dose mometasone furoate/formoterol fumarate MDI formulation and medium dose mometasone furoate DPI and MDI formulations in adults and adolescents with persistent allergic asthma.

A total of 90 subjects (15 per treatment) will be enrolled to ensure 12 subjects per treatment at the Day 14 evaluation, accounting for a 20% drop-out rate. A sample size of 12 subjects per treatment is required to detect a treatment difference of 28% in percent change of eNO at Day 14, assuming a pooled standard deviation of 20% with a power of 90%. These estimates are based on examination of eNO levels in asthmatic vs healthy subjects in an article written by S.A. Kharitonov et. al, 2003.

Subjects will be randomized to one of six treatment groups (MF/F MDI 100/10 mcg BID, MF/F MDI 200/10 mcg BID, MF/F MDI 400/10 mcg BID, MF DPI 200 mcg BID, MF MDI 200 mcg BID, or Placebo MDI BID) according to an SPRI computer-generated randomization schedule. Randomization will be performed in appropriately sized blocks using random numbers generated by SAS.

Intervention(s) in this Clinical Trial

• Drug: mometasone furoate/formoterol 100/10 mcg
  • mometasone furoate/formoterol 100/10 mcg BID (two inhalations of MF/F 50/5 from a metered-dose inhaler) for 14 days
• Drug: mometasone furoate/formoterol 200/10 mcg
  • mometasone furoate/formoterol 200/10 mcg BID (two inhalations of MF/F 100/5 from a metered-dose inhaler) for 14 days
• Drug: mometasone furoate/formoterol 400/10 mcg
  • mometasone furoate/formoterol 400/10 mcg BID (two inhalations of MF/F 200/5 mcg from a metered-dose inhaler) for 14 days
• Drug: MF DPI 200 mcg
  • MF DPI 200 mcg BID (one inhalation of MF DPI 200 mcg) for 14 days
• Drug: MF MDI 200 mcg
  • MF MDI 200 mcg BID (two inhalations of MF MDI 100 mcg) for 14 days
• Drug: Placebo
  • MF/F MDI placebo BID (2 inhalations)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: MF/F Arm 1
• Experimental: MF/F Arm 2
• Experimental: MF/F Arm 3
• Experimental: MF Arm 1
• Experimental: MF Arm 2
• Experimental: Placebo

Primary Measures

• Percent change from Baseline to Day 14 eNO.
  • Time Frame: Day 14
    Safety Issue?: No

Secondary Measures

• Percent change from Baseline to Day 7 in eNO.
  • Time Frame: Day 7, Day 14, Day 15
    Safety Issue?: No
• Percent change from Baseline to Day 14 in sputum eosinophil count.
  • Time Frame: Day 7, Day 14, Day 15
    Safety Issue?: No
• Change from Baseline to Day 15 in PD15 of mannitol challenge.
  • Time Frame: Day 7, Day 14, Day 15
    Safety Issue?: No
• Change from Baseline AM and PM asthma symptoms at Days 1-15.
  • Time Frame: Day 7, Day 14, Day 15
    Safety Issue?: No
• Change from Baseline AM and PM PEF at Days 1-15.
  • Time Frame: Day 7, Day 14, Day 15
    Safety Issue?: No

Inclusion Criteria:

• To document asthma diagnosis, historical reversibility defined as an increase in absolute FEV1 of >= 12% and >= 200 mL must have been performed within 12 months of Screening. For subjects without historical reversibility, one of the following methods can be used at the Screening Visit or at any time before the Baseline Visit:
• Demonstration of an increase in absolute FEV1 of at least 12% and a volume increase of at least 200 mL within 15-20 min after administration of 4 inhalations of albuterol/salbutamol (total dose 360 to 400 mcg) or of nebulized
• SABA (2.5 mg), if confirmed as standard office practice, OR
• Demonstration of a peak expiratory flow (PEF) variability of more than 20% expressed as a percentage of the mean highest and lowest morning prebronchodilator PEF over at least 1 week, OR
• Demonstration of a diurnal variation PEF of more than 20% based on the difference between the prebronchodilator (before taking albuterol/salbutamol) morning value and the postbronchodilator 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. {The calculation formula: Diurnal PEF
• Variation = Absolute [(highest of 3 readings, PM Post-BD PEF from prior evening)
• (highest of 3 readings, AM Pre-BD from morning value)]/[(highest PM Post-BD + highest AM Pre-BD)/2] * 100}
• At Screening and Baseline Visits, a subject must have persistent allergic asthma with an FEV1 >65% predicted.
• A subject must be allergic to at least one common allergen (grasses, trees, weeds, house dust mites, molds, dog and cat) as demonstrated by clinical symptoms when exposed to the allergen(s), and by skin prick testing or a RAST class >1 (excluding mRAST) within 2 years of inclusion in the study.
• If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject's current asthma therapy, the subject and/or parent/guardian) must agree to discontinue prescribed ICS, anticholinergics, leukotriene receptor inhibitors, and long-acting beta-2 agonists at the Screening Visit as per required washouts, and be transferred to treatment with SABA for relief for 2 weeks before the Baseline/Randomization Visit.
• Clinical laboratory tests (complete blood count, blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator.
• An electrocardiogram (ECG) performed at the Screening Visit or within 30 days prior to Screening Visit must be clinically acceptable to the investigator and have a QTc interval <440 msec for males and <450 msec for females.
• At Screening or any time prior to Baseline, a subject must have an eNO level of >30 ppb at a flow rate of 50 mL/second.
• At Screening or any time before Baseline, a subject must have a sputum eosinophil count >3% of total cell count.
• Willingness to give written informed consent and ability to adhere to dose and visit schedules. A subject 12 to 17 years of age must also provide written assent.
• A nonpregnant female subject of childbearing potential (with a negative serum pregnancy test at Screening) must use a medically acceptable, adequate form of birth control. If not currently sexually active she must agree to use a double-barrier method if she becomes sexually active during the study.

Exclusion Criteria:

• Use of systemic glucocorticosteroids within 3 months before Screening.
• Upper or lower respiratory tract infection within 4 weeks before Screening.
• Decrease in absolute FEV1 >20% between Screening and Baseline Visits.
• Requirement for > 8 inhalations per day of SABA MDI, or 2 or more nebulized treatments of 2.5 mg SABA, on any 2 consecutive days between the Screening and Baseline Visits.
• A decrease in AM or PM PEF below the Run-in Period stability limit on any 2 consecutive days before Baseline. At Visit 1, the Run-in Period stability limit for
• PEF will be established based on the subject's personal best. If the subject does not have a historical personal best, the historical PEF measurement will be the PEF predicted based on the subject's sex, age, and height. PEF value to be multiplied by 0.70 to determine stability limit.
• A clinical asthma exacerbation defined as a clinical deterioration of asthma that results in emergency treatment, hospitalization for asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids but allowing SABA), as per investigator, between Screening and Baseline Visits.
• Inability to induce sputum after 1 or 2 trys.

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

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

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00635882

Study ID Number: P05122

ClinicalTrials.gov Identifier: NCT00635882

Health Authority: United States: Food and Drug Administration