Study of Mometasone Furoate/Formoterol Combination and Fluticasone/Salmeterol in Persistent Asthmatics Previously Treated With Inhaled Glucocorticosteroids (Study P04139AM1)(COMPLETED)

Condition(s) targeted: Asthma

Intervention: mometasone furoate combination MDI 200/10 mcg BID (Drug); mometasone furoate combination MDI 400/10 mcg BID (Drug); Fluticasone/Salmeterol 250/50 mcg BID (Drug); Fluticasone/Salmeterol 500/50 mcg BID (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Schering-Plough

Official(s) and/or principal investigator(s):
Hendrik Nolte, Study Director, Affiliation: Director, Allergy/Respiratory Diseases/Clinical Immunology

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.

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

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

Primary outcome: The number and percent of all randomized subjects reporting adverse events.

Secondary outcome: 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.

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Starting date: June 2006
Ending date: November 2007
Last updated: February 29, 2008