Study of Mometasone Furoate/Formoterol Combination and Fluticasone/Salmeterol in Persistent Asthmatics Previously Treated With Inhaled Glucocorticosteroids (P04139)

Organon

Status and phase: Completed; Phase 3

Conditions: Asthma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00379288

P04139

Details and patient eligibility

About

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.

Enrollment: 404 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Key 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 has ever required ventilator support for respiratory failure secondary to asthma.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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404 participants in 4 patient groups

MF/F 200/10 mcg BID

Experimental group

Treatment:

Drug: mometasone furoate combination MDI 200/10 mcg BID

MF/F 400/10 mcg BID

Experimental group

Treatment:

Drug: mometasone furoate combination MDI 400/10 mcg BID

F/SC 250/50 mcg BID

Active Comparator group

Treatment:

Drug: Fluticasone/Salmeterol 250/50 mcg BID

F/SC 500/50 mcg BID

Active Comparator group

Treatment:

Drug: Fluticasone/Salmeterol 500/50 mcg BID