Official Title: “A 1-Year Safety Study of Medium and High Doses of Mometasone Furoate/Formoterol Combination Formulation and Medium and High Doses of Fluticasone/Salmeterol in Persistent Asthmatics Previously Treated With Medium to High Doses of Inhaled Glucocorticosteroids”

The purpose of this study is to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) metered dose inhaler (MDI) 200/10 mcg twice-a-day (BID) and MF/F MDI 400/10 mcg BID and two doses of fluticasone/salmeterol combination (F/SC) (250/50 mcg BID and 500/50 mcg BID) in subjects with persistent asthma who require maintenance treatment on inhaled glucocorticosteroids (ICS); evaluator-blind.

In addition, the extrapulmonary effects on 24-hour plasma cortisol area under curve (AUC), of MF/F MDI 200/10 mcg BID, MF/F MDI 400/10 mcg BID, F/SC MDI 250/50 mcg BID, and F/SC MDI 500/50 mcg BID will be evaluated.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2007

Intervention(s) in this Clinical Trial

• Drug: mometasone furoate combination MDI 200/10 mcg BID
  • MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 1 year
• Drug: mometasone furoate combination MDI 400/10 mcg BID
  • MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 1 year
• Drug: Fluticasone/Salmeterol 250/50 mcg BID
  • FS/c 250/50 twice daily for 1 year
• Drug: Fluticasone/Salmeterol 500/50 mcg BID
  • FS/C 500/50 twice daily for 1 year

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: MF/F 200/10 mcg BID
• Experimental: MF/F 400/10 mcg BID
• Active Comparator: F/SC 250/50 mcg BID
• Active Comparator: F/SC 500/50 mcg BID

Primary Measures

• The number and percent of all randomized subjects reporting adverse events.
  • Time Frame: 1 year
    Safety Issue?: Yes

Secondary Measures

• 24-hr plasma cortisol AUCs (based on data collected) & ECGs summarized using descriptive statistics. Number & percent randomized subjects w/newly developed cataracts (graded by LOCS III), & intraocular pressure >=22 mm Hg, summarized by treatment group.
  • Time Frame: 1 year
    Safety Issue?: Yes

Inclusion Criteria:

• Subjects of either sex and any race, at least 12 years of age, with a diagnosis of asthma of at least 12 months.
• Use of medium or high daily dose of ICS (alone or in combination with long-acting beta-agonist [LABA]) for at least 12 weeks prior to Screening and have been on a stable regimen for at least 2 weeks prior to Screening.
• Medium daily doses of ICS:
• > 500 to 1000 mcg beclomethasone chlorofluorocarbon (CFC)
• > 250 to 500 mcg beclomethasone hydrofluoroalkane (HFA)
• > 600 to 1000 mcg budesonide dry powder inhaler (DPI)
• > 1000 to 2000 mcg flunisolide
• > 250 to 500 mcg fluticasone
• 400 mcg MF
• > 1000 to 2000 mcg triamcinolone acetonide
• High daily doses of ICS:
• > 1000 mcg beclomethasone CFC
• > 500 mcg beclomethasone HFA
• > 1000 mcg budesonide DPI
• > 2000 mcg flunisolide
• > 500 mcg fluticasone
• > 400 mcg MF
• > 2000 mcg triamcinolone acetonide
• If there is no inherent harm in changing the subject's current asthma therapy, the subject must discontinue prescribed ICS or ICS/LABA combination at Baseline.
• Must show evidence of reversibility within the last 12 months or during the Screening
• Period. Historical reversibility defined as an increase in absolute forced expiratory volume in 1 second (FEV1) of >= 12% and >= 200 mL will qualify if performed within 12 months of Screening. If no historical reversibility, subject must demonstrate an absolute FEV1 of >= 12% and >= 200 mL within 10 to 15 minutes after four puffs of salbutamol at Visit 1 or anytime prior to Baseline.
• At Screening and Baseline, FEV1 must be >= 50% predicted, when restricted medications are withheld for the appropriate intervals.
• Complete blood count, blood chemistries, urinalysis, and electrocardiogram (ECG) conducted at Screening must be within normal limits or clinically acceptable to the investigator/sponsor. A chest x-ray performed at Screening or within 12 months prior must be clinically acceptable.
• A female of childbearing potential must be using a medically acceptable, adequate form of birth control:
• prescribed hormonal contraceptives;
• medically prescribed intrauterine device (IUD);
• medically prescribed transdermal contraceptive;
• condom in combination with spermicide;
• monogamous relationship with a male partner who has had a vasectomy.
• Birth control must have started at least 3 months prior to Screening. Subject must agree to continue its use for the duration of the study. A subject of childbearing potential who is not currently sexually active must agree to use a medically acceptable method should she become sexually active during the study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A subject of childbearing potential must have a negative serum pregnancy test at Screening.

Exclusion Criteria:

• A change (increase or decrease) in absolute FEV1 of > 20% at any time from the Screening Visit up to, and including, the Baseline Visit.
• A subject who requires the use of > 12 inhalations per day of short-acting beta-agonist (SABA) MDI or > 2 nebulized treatments per day of 2.5 mg salbutamol, on any 2 consecutive days from the Screening Visit up to, and including, the Baseline Visit.
• A subject who experiences a clinical asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication [other than SABA]) at any time from the Screening Visit up to, and including, the Baseline Visit.
• A subject who is a smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history > 10 pack-years.

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 Study Director Director, Allergy/Respiratory Diseases/Clinical Immunology  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00379288

Study ID Number: P04139

ClinicalTrials.gov Identifier: NCT00379288

Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica