Did the subject meet all the entry criteria? - Inclusion Criteria
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Informed consent: Subjects must give their signed and dated written informed consent to participate (1)
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Type of Subject: Outpatients 12 years of age or older at Visit 1. For sites in the following countries subjects will be >= 18 years of age: Germany, Poland, and other countries where local regulations or the regulatory status of study medication permit enrolment of adults only. Subjects must have a diagnosis of asthma as defined by the National Institutes of Health (NIH, 2007) at least 12 weeks prior to Visit 1. (2)
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Gender: Male or Eligible Female, defined as non- childbearing potential or childbearing potential using an acceptable method of birth control consistently and correctly, as defined by the following: (3)
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- Male partner who is sterile prior to the female subjects entry into the study and is the sole sexual partner for that female subject (4)
- Any intrauterine device (IUD) with a documented failure rate of less than 1% per year (8)
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- Double barrier method - spermacide plus a mechanical barrier (e.g., spermacide plus a male condom or a spermacide and female diaphragm). (9)
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- Oestrogenic vaginal ring (10)
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- Percutaneous contraceptive patches (11)
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- 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) (12)
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- 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 for females of childbearing potential at the initial screening vsit (Visit 1) and Visit 7 or Early Withdrawal. In addition a urine pregancy test will be performed on all females of childbearing potential at randomisation (Visit 3) and Follow- up Visit (Visit 8). (13)
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Severity of Disease: A best pre- bronchodilator FEV, of 40% - 90% of the predicted nromal value at the Visit 1 screening visit. Predicted values will be based upo NHANES III (Hankinson, 1999). If a subject is recorded as having Hispanic or Latino ethnicity, then the Mexian- American equations will be used (irrespective of race). If a subject is recorded as being of African- American/ African heritage race, then the African- American equation will be used. If a subject is recorded as being of Asian race, then the Asian adjustment will be used (Hankinson, 2010). Otherwise, the Caucasian equations will be used. (4)
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Reversibility of Disease: Demonstrated >= 12% and >= 200mL reversibility of FEV1 within 10 - 40 minutes following 2 - 4 inhalations of albuterol/ salbutamol inhalation aerosol (or equivalent nebulized treatment with albuterol/ salbutamol solution) at the Screening Visit (5)
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Current Anti- Asthma Therapy: All subjects must be using an ICS with or without LABA for at least 12 weeks prior ti Visit 1. (6)
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Two populations are eligible for enrolment: (17)
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Subjects maintained on a stable ICS dose (FP 100 - 250mcg twice daily or equivalent) for at least 4 weeks prior to Visit 1. (18)
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OR (19)
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Subjects must be maintained on a stable dose of an ICS/ LABA low- dose combination product (e. g., Seretide/ Advair 100/ 50 twice daily or equivalent via other combination products or via separate inhalers) for at least 4 weeks prior to Visit 1. Subjects taking Symbicort as needed must switch to Symbicort maintenance dosing with use of a short acting beta2 agonist (SABA) for symptom relief at least 4 weeks prior to Visit 1. (20)
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LABA therapy is not permitted beginning on the day of Visit 1 (last dose of LABA to be taken on day prior to Visit 1). Combination therapy must be stopped at Visit 1 and subjects switched to the same ICS dose of the same ICS for the run- in- period. (21)
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Short- Acting Beta2- Agonists (SABA): All subjects must be able to replace their current SABA treatment with albuterol/ salbutamol aerosol inhaler at Visit1 for use as needed for the duration of the study. Subjects must be able to withhold albuterol/ salbutamol for at least 6 hours prior to study visits. (7)
Did the subject meet all the entry criteria? - Exclusion Criteria
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History of Life- threatening asthma: Defined for this protocol as an asthma episode that required intubation and/ or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 10 years (1)
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Respiratory Infection: Culture- documented ar suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subjects asthma status or the subjects ability to participate in the study. (2)
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Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1. (3)
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Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnomalities other than asthma. (4)
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Other Concurrent Diseases (5)
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Abnormalities: (6)
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A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator,m would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/ disease exacerbated during the study. (7)
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Oropharygeal Examination: A subject will not be eligible for the run- in if the he/ she has clinical visual evidence of canididas at Visit 1. (6)
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Investigational Medications: A subject must not have used any Investigational drug within 30 days prior to Visit1 or within five half- lives (t1/2) of the prior investigational study (which ever is longer of the two) (7)
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Allergies: (8)
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- Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2- agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constitutes of the Novel DPI (i.e. lactose or magnesium stearate). (11)
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- Milk Protein Allergy: History of severe milk protein allergy. (12)
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Concomitant Medication: Administration of prescription or over the counter medications that would significantly affect the course of asthma, or interact with study drug, such as: anticonvulsivants (barbiturates, hydantoins, carbamazepine); polycyclic antidepressants; beta- adrenergic blocking agents; phenothiazines and monoamine oxidase (MAO) inhibitors. (9)
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- Immunosuppressive Medications: A subject must not be using or require use of immunosuppressive medications during the study. (Immunotherapy for the treatment of allergies is allowed during the study provided it was initiated 4 weeks prior to Visit 1 and subjects remain in the maintenance phase for the duration of the study.) (14)
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- Cytochrome P450 3A4 (CYP3A4) inhibitors: Subjects who have received a potent CYP3A4 inhibitor within 4 weeks of Visit (e.g., ritronavir, ketoconazole, itraconzole). (15)
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Compliance: A subject will not be eligibile if he/ she or his/ her parent or legal guardian has any infirmity, disabilitxý, disease, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily diaries. (10)
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Tobacco Use: Current smoker or a smoking history of 10 pack years (e.g., 20 cigarettes/ day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars or pipe tobacco). (11)
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Affiliation with Investigators 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. (12)
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Previous Participation: A subject may not have previously been randomized to treatment in another Phase III fluticasone furoate/ GW642444 combination product study (i.e. HZA106829, HZA106837, HZA106839, HZA106851, HZA113091). (13)
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Night shift workers: No subject is permitted to perform night shift work for 1 week prior to Visit 1 until completion of the study treatment period. (14)