Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04073AM1)

Condition(s) targeted: Asthma

Intervention: mometasone furoate/formoterol fumarate combination MDI 100/10 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 100 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 Low-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 that is consistent with

the following: Diagnosis based on clinical history & examination, pulmonary function parameters & response to beta-2-agonists, according to international guidelines.

- Been using low daily dose of ICS (either alone or in combination with LABA) >=12 weeks

& been on stable asthma regimen for >=2 weeks prior to Screening. Low daily doses of ICS are:

200-500 mcg beclomethasone CFC 100-250 mcg beclomethasone HFA 200-600 mcg budesonide DPI 500-1000 mcg flunisolide 100-250 mcg fluticasone 200 mcg MF 400-1000 mcg triamcinolone acetonide 80 to 160 mcg ciclesonide Note: Dose delivery by method/modality other than these must be equivalent.

- No harm in changing current asthma therapy to investigator, subject (legal

representation, if applicable) must be willing to discontinue his/her ICS or ICS/LABA combination prior to initiating MF MDI run-in medication at Screening Visit, & transferred to open-label treatment with MF MDI 100 mcg BID for 2-3 weeks prior to Baseline Visit.

- To document diagnosis of asthma & assure responsiveness to bronchodilators before

randomization 1 of these can be used at Screening Visit or thereafter, but prior to Baseline Visit:

Demonstrate increase in absolute FEV1 >=12% & >=200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose 360-400 mcg) or nebulized SABA (2. 5 mg) if confirmed as standard office practice, OR Demonstrate PEF variability >20% expressed as percentage of the mean highest & lowest morning prebronchodilator (before taking albuterol/salbutamol) PEF over >=1 week, OR Demonstrate diurnal variation in PEF of >20% based on difference between prebronchodilator (before taking albuterol/salbutamol) morning value & postbronchodilator value (after taking albuterol/salbutamol) from evening before, expressed as percentage of mean daily PEF value.

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

- At Baseline Visit, FEV1 must be >=60% & <=85% predicted when all restricted drugs have

been withheld for appropriate intervals.

- Lab tests at Screening Visit must be normal or acceptable to investigator/sponsor and

include serum pregnancy for females of child-bearing potential). ECG at Screening Visit, using centralized trans-telephonic technology must be acceptable to investigator. Chest x-ray performed at Screening Visit or within 12 months prior to Screening Visit must be acceptable to investigator.

- Subject (legal representation, if applicable) must be willing to give written informed

consent & able to adhere to schedules.

- A non-pregnant of childbearing potential must use birth control. Includes: hormonal

contraceptives including hormonal vaginal ring, hormonal implant or depot-injectable; IUD; medically prescribed topically-applied transdermal contraceptive patch; condom in combination with spermicide; monogamous relationship with male who had vasectomy. Started birth control method >=3 months prior to Screening (exception condom), & must agree to continue its use. Female of childbearing potential who is not currently sexually active must agree & consent to using birth control, should she become active. Women who have been surgically sterilized or are >=1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.

Exclusion Criteria:

- Increase/decrease in absolute FEV1 of >20% at any time from Screening Visit up to &

including Baseline Visit. PFTs will be performed in the morning.

- >8 inhalations/day of SABA MDI or >=2 nebulized treatments/day of 2. 5 mg SABA on 2

consecutive days from Screening Visit up to& including Baseline Visit.

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

prior to randomization.

- Asthma deterioration results in emergency treatment, hospitalization, or treatment

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

- Treated in ER (for severe asthma exacerbation requiring systemic glucocorticosteroid

treatment) or admitted to hospital for management of airway obstruction within last 3 months.

- Ever required ventilator support for respiratory failure secondary to asthma.

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

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

- Smoker or ex-smoker & has smoked within previous year or has cumulative smoking

history >10 pack-years.

- Significant abnormal vital sign.

- Evidence upon visual inspection of significant oropharyngeal candidiasis at Baseline

or earlier with or without treatment. If there is evidence at Screening or Pre-Baseline Visit, may be treated as appropriate & Baseline Visit can be scheduled upon resolution.

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

hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other which, in judgment of investigator, could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) insulin-dependent diabetes, hypertension being treated with beta-blockers, active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB [Fridericia or Bazett corrections, respectively >500 msecs), stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts (including prior cataract surgery), AIDS, or conditions that may interfere with respiratory function such as COPD, chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis. Others which are well-controlled & stable (eg hypertension not requiring beta-blockers) will not prohibit participation if deemed appropriate by investigator.

- Allergic/intolerant of glucocorticoids, beta-2-agonists, or any inactive excipients in

study drugs.

- Female who is breast-feeding, pregnant, or intends to become pregnant while in study.

- Illicit drug user.

- HIV positive (testing not done).

- Unable to use oral MDI inhaler.

- Has been taking any restricted medications prior to Screening without meeting required

washout.

- Cannot adhere to prohibited & permitted concomitant medications.

- May not participate in same study at another site. Cannot participate in different

study at any site, during same time.

- Must not be randomized into study more than once.

- No person directly associated with administration of study may participate.

- Previously participated in trial with MF/F.

Investigational Site 42, Rousse 7002, Bulgaria

Investigational Site 43, Plovdiv 4003, Bulgaria

Investigational Site 46, Sofia 1233, Bulgaria

Investigational Site 45, Plovdiv 4000, Bulgaria

Investigational Site 38, Sofia 1431, Bulgaria

Investigational Site 44, Plovdiv 4000, Bulgaria

Investigational Site 37, Sofia 1431, Bulgaria

Investigational Site 39, Sofia 1431, Bulgaria

Investigational Site 28, Toronto M4V 1R2, Canada

Investigational Site 29, Ottawa K1Y 4G2, Canada

Investigational Site 36, Mississauga L5A 3V4, Canada

Investigational Site 47, Bogota, Colombia

Investigational Site 48, Bogota, Colombia

Investigational Site 49, Bogota, Colombia

Investigational Site 50, San Jose, Costa Rica

Investigational Site 52, San Jose, Costa Rica

Investigational Site 53, Zagreb, Croatia

Investigational Site 54, Zagreb, Croatia

Investigational Site 58, Zagreb 10000, Croatia

Investigational Site 55, Zagreb 10000, Croatia

Investigational Site 56, Rijeka 51000, Croatia

Investigational Site 57, Zagreb 10000, Croatia

Investigational Site 59, Quito, Ecuador

Investigational Site 60, Guayaquil, Ecuador

Investigational Site 61, Tartu 51014, Estonia

Investigational Site 63, Tallinn 13619, Estonia

Investigational Site 65, Guatemala, Guatemala

Investigational Site 66, Guatemala, Guatemala

Investigational Site 67, Guamalate, Guatemala

Investigational Site 68, Komarom 2900, Hungary

Investigational Site 72, Deszk 6772, Hungary

Investigational Site 73, Miskolc 3526, Hungary

Investigational Site 70, Torokbalint, Hungary

Investigational Site 75, Nyiregyhaza 4412, Hungary

Investigational Site 76, Budapest 1095, Hungary

Investigational Site 77, Budapest 1095, Hungary

Investigational Site 69, Mosonmagyarovar 9200, Hungary

Investigational Site 71, Budapest 1121, Hungary

Investigational Site 74, Kecskemet 6000, Hungary

Investigational Site 79, Guadalajara 44280, Mexico

Investigational Site 78, Guadalajara 44100, Mexico

Investigational Site 81, Mexico 52763, Mexico

Investigational Site 87, Lodz 93-513, Poland

Investigational Site 94, Moscow 115478, Russian Federation

Investigational Site 95, Moscow 123128, Russian Federation

Investigational Site 96, Saint Petersburg 193231, Russian Federation

Investigational Site 97, Saint Petersburg 194291, Russian Federation

Investigational Site 100, Kazan 420012, Russian Federation

Investigational Site 101, 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

Investigational Site 1, KIRKLAND, Washington 98034, United States

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