A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Moderate-Dose ICS Therapy.

Subjects eligible for enrolment in the study must meet all of the following criteria:

Type of Subject: Outpatient

Age: 12 years of age or older at Visit 1. For sites in the following countries, subjects recruited will be ≥18 years of age: Bulgaria, Czech Republic, Germany, Greece, Lithuania, New Zealand, Russian Federation, Turkey and any other countries where local regulations or the regulatory status of study medication permit enrolment of adults only.

3\. Gender: Male or Eligible Female

To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:

Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject

Implants of levonorgestrel

Injectable progestogen

Oral contraceptive (either combined estrogen/progestin or progestin only)

Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.

Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial and for a period after the trial to account for elimination of the drug (minimum of six days).

Double barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm).

NB: For German sites, female subjects must use a method of birth control other than the double barrier method.

The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds)

Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation. A serum pregnancy test is required of all females. This test will be performed at the initial screening visit (Visit 1) and Visit 8. In addition, a urine pregnancy test will be performed on the evening of the double-blind treatment visit, prior to randomization (Visit 3) and at Visits 4 through 7.

Asthma Diagnosis: Asthma as defined by the National Institutes of Health \[National Institutes of Health, 2007\].

Severity of Disease: A best FEV1 of 40%-85% of the predicted normal value during the morning Visit 1 screening period or a best FEV1 of 40%-90% of the predicted normal value during the evening Visit 1 screening period.

Reversibility of Disease: Demonstrated a ≥ 12% and ≥200mL reversibility of FEV1 within approximately 30-minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers are permitted for reversibility testing only) or one nebulized albuterol/salbutamol solution during the screening period.

Current Anti-Asthma Therapy: Subjects must have been using a inhaled corticosteroid for at least 8 weeks prior to Visit 1 and maintained on a stable dose of inhaled corticosteroids for four weeks prior to Visit 1 at one of the following doses: \[fluticasone propionate MDI CFC/HFA \>176 ≤ 440mcg exactuator or \> 200 ≤500mcg ex valve\]; \[fluticasone propionate DPI \> 200≤500mcg\]; \[beclomethasone dipropionate DPI \> 420 ≤ 840mcg exactuator or \> 500 ≤ 1000mcg ex-valve\]; \[beclomethasone dipropionate HFA Qvar \> 160 ≤ 480mcg exactuator or \> 200 ≤ 500mcg ex-valve\]; \[budesonide DPI MDI \>400 ≤1200mcg\]; \[flunisolide \> 1000 ≤ 2000mcg\]; \[triamcinolone acetonide \>1000 ≤1600mcg\]; \[mometasone furoate DPI \>200 ≤ 440mcg\]; \[ciclesonide MDI HFA \>160 mcg ≤ 320mcg ex-actuator dose / \>200mcg ≤ 400mcg ex-valve dose}

Short- Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as needed for the duration of the study. The use of spacer devices with metered dose inhaler (MDI) or nebulized albuterol/salbutamol will not be allowed during the study with the exception of their use during reversibility testing at Visit 1. Subjects must be able to withhold all inhaled short-acting beta sympathomimetic bronchodilators for at least 6 hours prior to all study visits.

Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.

Compliance: Subjects must be able to comply with completion of the Daily Diary (includes paper medical conditions diary).

French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

At the end of the run-in period, a subject will be eligible to enter the treatment period of the study if he/she meets the following criteria at Visit 3:

1. Evening pre-dose percent predicted FEV1 of between 40% and 90% of their predicted normal.

2. Any combination of the daily asthma symptom scores (day-time plus night-time) of ≥1 or albuterol/salbutamol use on at least 4 of the last 7 consecutive days of the run-in period (immediately preceding Visit 3).

Tobacco Use : Current smoker or a smoking history of 10 pack years or more (e.g. 20 cigarettes/day for 10 years). A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco).

Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.

Corticosteroid Use: Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1.

Potent Cytochrome P450 3A4 (CYP3A4) inhibitors: Patients who are receiving potent CYP3A4 inhibitors within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).

What this study is about