Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04334AM1)

Condition(s) targeted: Asthma

Intervention: mometasone furoate/formoterol fumarate combination MDI 200/10 mcg BID (Drug); Mometasone furoate MDI (MF MDI) (Drug); formoterol fumarate 10 mcg (Drug); Placebo (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Schering-Plough

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

This is a randomized, multi-center, double-blind, double-dummy, placebo-controlled, parallel-group study, evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) versus MF for 26 weeks. Prior to the 26-week double-blind Treatment Period, subjects will receive open-label MF MDI 200 mcg twice daily (BID) for 2 to 3 weeks during the Run-in Period. Efficacy will be measured by mean change from Baseline to Week 12 in area under the forced expiratory volume in one second concentration time curve from 0 to 12 hours (FEV1 AUC[0-12 hr]).

Official title: A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Medium-Dose Inhaled Glucocorticosteroids

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: AUC(0-12 hr) of change from Baseline FEV1 for MF/F vs MF. Average of the 2 predose FEV1 measurements at Baseline will be subtracted from each of the serial measurements over the 12-hr. period.

Secondary outcome: For MF/F vs placebo: Change from Baseline in AQLQ(S) and ACQ total score and proportion of nights across the treatment period with nocturnal awakenings due to asthma which require use of SABA.

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

Criteria:

Inclusion Criteria:

- >=12 years, either sex, any race, asthma diagnosis >=12 months following: Diagnosis

based on clinical history & examination, pulmonary parameters & response to beta-2-agonists, according to international guidelines.

- Been using medium daily dose of ICS (either alone or in combination weeks & been on

stable asthma regimen for >=2 weeks prior to Screening. doses of ICS are:

>500-1000 mcg beclomethasone CFC >250-500 mcg beclomethasone HFA budesonide DPI >1000-2000 mcg flunisolide >250-500 mcg fluticasone >400 2000 mcg triamcinolone acetonide >160 to 320 mcg ciclesonide Note: Dose delivery method/modality other than these must be equivalent.

- No harm in changing current asthma therapy to investigator, subject must be willing to

discontinue his/her ICS or ICS/LABA combination initiating MF MDI run-in medication at Screening Visit, & transferred treatment with MF MDI 200 mcg BID for 2-3 weeks prior to Baseline

- To document diagnosis of asthma & ensure responsiveness to randomization 1 of these

can be used at Screening Visit or thereafter, but Visit: Demonstrate increase in absolute FEV1 >=12% & >=200 mL approximately after administration of 4 inhalations of albuterol/salbutamol (total dose of 360 nebulized SABA (2. 5 mg) if confirmed as standard office practice, OR Demonstrate variability >20% expressed as percentage of the mean highest & lowest morning prebronchodilator PEF over >=1 week, OR Demonstrate diurnal variation in on difference between prebronchodilator (before taking albuterol/salbutmaol) postbronchodilator (after taking albuterol/salbutamol) value from evening percentage of mean daily PEF value on any day during the open-label Run

- At Screening Visit, FEV1 must be >=60% & <=90% predicted.

- At Baseline Visit, FEV1 must be >=60% & <=85% predicted been withheld for appropriate

intervals.

- Lab tests at Screening Visit must be normal or acceptable to serum pregnancy for

females of child-bearing potential. ECG at Screening centralized trans-telephonic technology must be acceptable to investigator. performed at Screening Visit or within 12 months prior to Screening Visit acceptable to investigator.

- Subject (legal representation, if applicable) must be willing to give consent & able

to adhere to schedules.

- A non-pregnant female of childbearing potential must use birth contraceptives;

hormonal vaginal ring, hormonal implant or depot medically prescribed topically-applied transdermal contraceptive patch; combination with spermicide; monogamous relationship with male who Started birth control method = 3 months prior to Screening (exception agree to continue its use. Female of childbearing potential who is not currently active must agree & consent to using birth control, should she become have been surgically sterilized or are >=1 year postmenopausal are not childbearing potential. Female must have negative serum pregnancy test order to be considered eligible for the open-label MF MDI

Exclusion Criteria:

- Increase/decrease in absolute FEV1 of >20% while using ICS at any Visit up to &

including Baseline Visit.

- >8 inhalations/day of SABA MDI or >=2 nebulized treatments/day consecutive days from

Screening Visit up to& including Baseline Visit.

- Decrease in AM/PM PEF below Screening Period stability limit on any 2 consecutive days

prior to randomization.

- Asthma deterioration results in emergency treatment, hospitalization due to asthma, or

treatment with additional, excluded asthma medication (including oral or other systemic allowing SABA) as judged by investigator at any time from Screening including Baseline Visit.

- Treated in ER (for severe asthma exacerbation requiring systemic treatment) or

admitted to hospital for management of airway obstruction months.

- Ever required ventilator support for respiratory failure secondary to

- Upper/lower respiratory tract infection within previous 2 weeks prior to Baseline

Visits. Visits can be rescheduled 2 weeks after complete resolution.

- Smoker or ex-smoker & has smoked within previous year or has history >10 pack-years.

- Significant abnormal vital sign.

- Evidence upon visual inspection of significant oropharyngeal earlier with or without

treatment.

- History of significant renal, hepatic, cardiovascular, metabolic, ophthalmologic,

respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgement of investigator, could interfere with study or require treatment which might study. Examples include (but are not limited to) insulin-dependentbeing treated with beta-blockers, active hepatitis, coronary artery disease, significant QTc prolongation (ie QTcF or QTcB [Fridericia or Bazett corrections, respectively >500 msecs), stroke, severe rheumatoid arthritis, or posterior subcapsular cataracts (including prior cataract surgery), AIDS, that may interfere with respiratory function such as COPD, chronic bronchiectasis, cystic fibrosis. Others which are well-controlled & stable not requiring beta-blockers) will not prohibit participation if deemed appropriate investigator.

- Allergic/intolerant of glucocorticoids, beta-2-agonists, or any drugs.

- Female who is breast-feeding, pregnant, or intends to become pregnant

- Illicit drug user.

- HIV positive (testing not done).

- Unable to use oral MDI inhaler.

- Has been taking any restricted medications prior to Screening without washout.

- Cannot adhere to prohibited & permitted concomitant medications.

- May not participate in same study at another site. In addition, a subject cannot

participate in a different investigational study at any site, during the same timeframe of this study.

- Must not be randomized into study more than once.

- No person directly associated with administration of study may

- Previously participated in trial with MF/F.

Investigational Site 24, Quebec G1V 4M6, Canada

Investigational Site 26, Ottawa K1Y 4G2, Canada

Investigational Site 36, Mississauga L5A 3V4, Canada

Investigational Site 25, Toronto M4V 1R2, Canada

Investigational Site 47, Bogota, Colombia

Investigational Site 116, Bogota, Colombia

Investigational Site 117, Bogota, Colombia

Investigational Site 48, San Jose, Costa Rica

Investigational Site 50, San Jose, Costa Rica

Investigational Site 49, San Jose, Costa Rica

Investigational Site 51, Zagreb 10000, Croatia

Investigational Site 52, Zagreb 10000, Croatia

Investigational Site 53, Zagreb 10000, Croatia

Investigational Site 55, Zagreb 10000, Croatia

Investigational Site 56, Kantrida 53 51000, Croatia

Investigational Site 79, Copenhagen NV, Denmark

Investigational Site 79, Copenhagen, Denmark

Investigational Site 57, Quito, Ecuador

Investigational Site 58, Guayaquil, Ecuador

Investigational Site 59, Tartu 51014, Estonia

Investigational Site 60, Tallinn 13419, Estonia

Investigational Site 61, Tallinn 13619, Estonia

Investigational Site 62, Guatemala, Guatemala

Investigational Site 63, Guatemala, Guatemala

Investigational Site 64, Guatemala, Guatemala

Investigational Site 65, Komarom 2900, Hungary

Investigational Site 66, Mosonmagyarovar 9200, Hungary

Investigational Site 67, Torokbalint, Hungary

Investigational Site 68, Budapest 1121, Hungary

Investigational Site 69, Deszk 6772, Hungary

Investigational Site 70, Miskolc 3526, Hungary

Investigational Site 71, Kecskemet 6000, Hungary

Investigational Site 72, Nyiregyhaza 4412, Hungary

Investigational Site 73, Budapest 1095, Hungary

Investigational Site 74, Budapest 1122, Hungary

Investigational Site 75, Guadalajara 44100, Mexico

Investigational Site 76, Guadalajara 44280, Mexico

Investigational Site 78, Mexico 52763, Mexico

Investigational Site 206, Monterrey, N.L., Mexico

Investigational Site 82, Katowice 40-752, Poland

Investigational Site 84, Olawa, Poland

Investigational Site 85, Lodz 93-513, Poland

Investigational Site 86, Pozan 60-693, Poland

Investigational Site 92, Moscow 115478, Russian Federation

Investigational Site 93, Moscow 123128, Russian Federation

Investigational Site 94, Saint Petersburg 193231, Russian Federation

Investigational Site 95, Saint Petersburg 194291, Russian Federation

Investigational Site 97, Moscow 125206, Russian Federation

Investigational Site 98, Kazan 420012, Russian Federation

Investigational Site 99, Saint Petersburg 197022, Russian Federation

Investigational Site 124, Saint Petersburg 194291, Russian Federation

Investigational Site 125, Saint Petersburg 198216, Russian Federation

Investigational Site 16, Normal, Illinois 61761, United States

Starting date: September 2006
Ending date: September 2008
Last updated: June 16, 2008