Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04431AM2)(COMPLETED)

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00381485
• Date of registration: 26/09/2006
• Primary sponsor: Schering-Plough
• Public title: Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04431AM2)(COMPLETED)
• Scientific title: A 12-Week Efficacy and Safety Study of Two Doses of Mometasone Furoate/Formoterol Combination Formulation Compared With Mometasone Furoate Monotherapy, in Persistent Asthmatics Previously Treated With High-Dose Inhaled Glucocorticosteroids
• Date of first enrolment: July 2006
• Target sample size: 834
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00381485
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Countries of recruitment

Argentina, Bulgaria, Canada, Chile, Colombia, Denmark, Honduras, Hungary, Peru, Poland, Russian Federation

Key inclusion & exclusion criteria

Inclusion Criteria:

- A subject must be at least 12 years of age, of either sex, and of any race, with a
diagnosis of asthma of at least 12 months duration that is consistent with the
following definition:

- The diagnosis of asthma is based upon clinical history and examination,
pulmonary function parameters, and response to beta2-agonists, according to
international guidelines.

- A subject must have been using a high dose of inhaled glucocorticosteroid (ICS)
either alone or in combination with a long-acting beta2 agonist (LABA) for at least
12 weeks prior to Screening, with no use of oral glucocorticosteroids within 30 days
prior to Screening. A subject must have been on a stable asthma regimen (daily dose
unchanged) for at least 2 weeks prior to Screening. High daily doses of ICS are
defined as follows:

- >1000 mcg beclomethasone chlorofluorocarbon (CFC)

- >500 mcg beclomethasone hydrofluoroalkane (HFA)

- >1000 mcg budesonide dry powder inhaler (DPI)

- >2000 mcg flunisolide

- >500 mcg fluticasone

- >400 mcg MF

- >2000 mcg triamcinolone acetonide

- >320 mcg ciclesonide

Note: Dose delivery by method or modality other than those noted above must be equivalent.

- A subject must have experienced at least one severe exacerbation requiring a course
of oral glucocorticosteroid 2 to 12 months prior to Screening.

- If, based upon the medical judgment of the investigator, there is no inherent harm in
changing the subject's current asthma therapy, then the subject (and parent/guardian,
if applicable) must be willing to discontinue his/her prescribed ICS or ICS/LABA
prior to initiating MF MDI run-in medication.

- To document the diagnosis of asthma and assure the subject's responsiveness to
bronchodilators before randomization, one of the following methods can be used at the
Screening Visit, Day-14, or thereafter, but prior to the Baseline Visit:

- The subject must demonstrate an increase in absolute FEV1 of at least 12% and at
least 200 mL within approximately 15 to 20 minutes after administration of four
inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg).

- The subject must demonstrate a peak expiratory flow (PEF) variability of more
than 20% expressed as a percent of the best and lowest morning
pre-bronchodilator PEF over at least 1 week.

- The subject must demonstrate a diurnal variation in 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. Note: If a subject is to qualify using diurnal
variation, the subject should be instructed to perform his/her PEF evaluation
after using his/her bronchodilator in the evening.

- At the Screening Visit, the subject's FEV1 must be >=50% predicted when all
restricted medications have been withheld for the appropriate intervals.

- At the Baseline Visit, the subject's FEV1 must be >=50% and <=85% predicted when all
restricted medications have been withheld for the appropriate intervals.

- The subject (and parent/guardian for a subject under the age of legal consent) must
be willing to give written informed consent and be able to adhere to dose and visit
schedules.

- A female subject of childbearing potential must be using a medically acceptable,
adequate form of birth control. This includes:

- hormonal contraceptive as prescribed by a physician (oral combined, hormonal
vaginal ring, hormonal implant or depot-injectable);

- medically prescribed intra-uterine device (IUD);

- medically prescribed topically-applied transdermal contraceptive patch;

- condom in combination with a spermicide (double-barrier method);

- monogamous relationship with a male partner who has had a vasectomy. The
subject must have started this birth control method at least 3 months prior to
Screening (with the exception of condom in combination with spermicide), and
must agree to continue its use for the duration of the study. A female subject
of childbearing potential who is not currently sexually active must agree and
consent to using a medically acceptable method should she become sexually active
during the course of this study. Women who have been surgically sterilized or
are at least 1 year postmenopausal are not considered to be of childbearing
potential. A female subject of childbearing potential must have a negative
serum pregnancy test at Screening in order to be considered eligible for the
open-label MF MDI Run-in Period.

Exclusion Criteria:

- A subject who demonstrates a change (increase or decrease) in absolute FEV1 of >20%
at any time from the Screening Visit up to and including the Baseline Visit.
Pulmonary function tests (PFTs) will be performed in the morning.

- A subject who requires the use of >8 inhalations per day of short-acting beta
agonists (SABA) MDI or >=2 nebulized treatments per day of 2.5 mg SABA, on any 2
consecutive days from the Screening Visit up to and including the Baseline Visit.

- A subject who experiences a decrease in AM or PM peak expiratory flow (PEF) below the
Run-in Period stability limit on any 2 consecutive days prior to randomization.

- 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 [including oral or other
systemic corticosteroids, but allowing SABAs]), at any time from the Screening Visit
up to and including the Baseline Visit.

- A subject who has been treated in the emergency room (for a severe asthma
exacerbation), or admitted to the hospital for management of airway obstruction,
within the last 3 months.

- A subject who has ever required ventilator support for respiratory failure secondary
to asthma.

- A subject who has experienced an upper or lower respiratory tract infection (viral or
bacterial) within the previous 2 weeks prior to Screening and Baseline Visits. Visits
can be rescheduled 2 weeks after complete resolution of the event to re-assess
eligibility.

- A subject who is a smoker or ex-smoker and has smoked within the previous year or has
had a cumulati


Age minimum: 12 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Drug: Mometasone furoate MDI (MF MDI)

Drug: Mometasone furoate/formoterol (MF/F) combination

Primary Outcome(s)

Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) [Time Frame: Baseline to Week 12]

Secondary Outcome(s)

Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma That Require Use of Short-Acting Beta Agonists (SABA) [Time Frame: 12-week Treatment Period]

Change From Baseline to Week 12 in Asthma Control Questionnaire (ACQ) Total Score [Time Frame: Baseline to Week 12]

Change From Baseline to Week 12 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score [Time Frame: Baseline to Week 12]

Secondary ID(s)

Doc ID: 3166301

EUDRACT No.: 2005-005910-20

P04431

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Novartis