ong-Term Safety Study of Fluticasone Furoate/GW642444
- Conditions
- AsthmaMedDRA version: 14.1Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2009-012054-20-Outside-EU/EEA
- Lead Sponsor
- GlaxoSmithKline Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 503
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.Type of Subject: Outpatient
2.Age: 12 years of age or older at Visit 1 (or 18 years of age or older if 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 levonorgetrel or etonogestrel
•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
•Estrogenic vaginal ring
•Double barrier method – spermicide plus a mechanical barrier (e.g. spermicide plus a male condom or spermicide and female diaphragm)
•Percutaneous contraceptive patches
•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)
•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 visit (Visit 1), Visit 6, Visit 8, and Visit 11/Early Withdrawal. A urine pregnancy test will be performed at Visits 2 through 5, Visit 7, Visit 9, Visit 10 and follow-up contact.
4.Asthma Diagnosis: A diagnosis of asthma as defined by the National Institutes of Health [NIH, 2007] at least 12 weeks prior to Visit 1.
5.Severity of Disease: A best FEV1 of =50% of the predicted normal value at Visit 1. NHANES III predicted values will be used for subjects =12 years of age [Hankinson, 1999]. If a subject is recorded as having Hispanic or Latino ethnicity, then the Mexican-American equations will be used (irrespective of race). If a subject is recorded as being African American/African Heritage race, then the African American equations will be used. Otherwise, the Caucasian equations will be used.
6.Reversibility of Disease: Historical documentation within 12 months or currently demonstrated a =12% and =200mL reversibility of FEV1 within approximately 10 to 40 minutes following 2 to 4 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers are permitted for reversibility testing only) or equivalent nebulized treatment with albuterol/salbutamol solution at screening.
7.Current Anti-Asthma Therapy: Subjects must be using an approved dose of an ICS (as per specific prescribing information) with or without an additional controller medication (i.e., long-acting beta-agonist, leukotriene modifier, etc.) for at least four weeks prior to Visit 1. See Table 1 in protocol for examples of allowed doses of commonly used ICS.
8.Short-Acting Beta2-Agonists: All subjects must be able to replace 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 device with MDI or nebulized albuterol/salbutamol will not be allowed during the study with the e
Subjects meeting any of the following criteria must not be enrolled in the study:
1.History of Life-Threatening Asthma: i.e. an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures in the past 5 years.
2.Asthma Exacerbation requiring systemic corticosteroids within 3 months of Visit 1 or overnight hospitalization for asthma within 6 months prior to Visit 1.
3.Concurrent Respiratory Disease: pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or respiratory abnormalities other than asthma.
4.Clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study (see protocol for further detail).
5.Visual evidence of oral candidiasis
6.Participation in a study or use of an investigational drug within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior investigational study (whichever is longer of the two).
7.Previous Participation: previous randomization to treatment in a Phase III Fluticasone Furoate/GW642444 Inhalation Powder study (if a subject is a screen failure or run-in failure from another Phase III Fluticasone Furoate/GW642444 Inhalation Powder study, they are eligible for this study).
8.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 constituents of the Novel Dry Powder Inhaler (i.e., lactose or magnesium stearate).
9.Milk Protein Allergy: History of severe milk protein allergy.
10.Immunospressive medications: use of or requirement for immunosuppressive medications during the study.
Note: 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.
11.Attendance: infirmity, disability or geographical location which seems likely (in the opinion of the investigator) to impair compliance with any aspect of this study protocol or scheduled visits to the study center and non-compliance with study medication or procedures (i.e., completion of diary card).
12.Neurological or psychiatric disease or history of drug or alcohol use which would interfere with the subject’s proper completion of the protocol requirements.
13.Concomitant Medications: Administration of prescription or over the counter medication which would significantly affect the course of asthma, or interact with sympathomimetic amines
14.Use of inhaled tobacco products within the past three months or historical use of 10 pack years or more.
15.Immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
16.Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1.
17.A subject is not eligible if he/she is receiving a potent CYP 3A4 inhibitor within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).
18.Nightshift Workers.
Exclusion Criteria for Randomization to Treatment (
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of 12 months treatment with two strengths of Fluticasone Furoate/GW642444 Inhalation Powder once-daily in the evening in subjects 12 years of age and older with asthma.;Secondary Objective: N/A;Primary end point(s): No specific safety endpoint has been defined as primary; a holistic approach is taken to assess the objective defined above with all safety endpoints being of equal importance. The relative safety of each Fluticasone Furoate/GW642444 Inhalation Powder group and fluticasone propionate 500mcg twice daily will be evaluated by assessing the overlap in the confidence intervals for the treatment effects relative to a marketed benchmark, fluticasone propionate. Statistical modelling will be performed, where appropriate, in order to provide greater understanding for some endpoints.;Timepoint(s) of evaluation of this end point: 52 Weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Not Applicable;Timepoint(s) of evaluation of this end point: Not Applicable