A 12-Week Dose-ranging Study to Evaluate the Effectiveness and Safety of Fp Spiromax® given Orally Twice Daily compared with a non-active drug in Adolescent and Adult Subjects with Severe Persistent Asthma Uncontrolled on High dose Inhaled Corticosteroid Therapy.
- Conditions
- Severe Persistent AsthmaTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2010-023601-35-BE
- Lead Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1. Informed consent/assent: For adult patients, written informed consent signed and dated by the patient before conducting any study related procedures; for minor patients, written informed consent signed
and dated by the parent/legal guardian and written assent signed and dated by the patient before conducting any study related procedure.
2. Male or female 12 years and older, as of the Screening Visit. Male or female 18 years and older, as of the Screening Visit, in countries where local regulations or the regulatory status of study medication permit enrollment of adults only.
3. General good health, free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the subject at increased risk during the study.
4. Asthma Diagnosis: Asthma as defined by the National Institutes of Health.
5. Severity of Disease: A best forced expiratory volume in one second (FEV1) of 40%-85% of the predicted normal value during the Screening Visit. NHANES III predicted values will be used for subjects aged =12
years and adjustments to predicted values will be made for African American subjects. American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria for acceptability, repeatability, and end of test must be met for spirometry.
6. Reversibility of Disease: Demonstrated a =12% reversibility of FEV1 within 30 minutes following 2-4 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers and nebulized albuterol are permitted for reversibility testing only) at the Screening Visit. If subjects fail to demonstrate an increase in FEV1 =12% then subjects are not eligible for the study; however, based on investigator judgment, they will be allowed to retest once within 7 days and rescreen once after 7
days. Reversibility values of 11.50 – 11.99 will be rounded to 12. Documented historical reversibility of = 12% within 1 year of the Screening Visit will be accepted.
7. Current Asthma Therapy: Subjects will be required to be on a short acting ß2 agonist and inhaled corticosteroid for a minimum of 8 weeks before the Screening Visit and have been maintained on a stable dose of inhaled corticosteroids (either as ICS mono or as ICS/LABA combination therapy) for 4 weeks prior to the Screening Visit at 1 of the following qualifying ICS doses (see protocol for details of qualifying doses).
8. Short-Acting ß2-Agonists: All subjects must be able to replace their current short-acting ß2-agonists with albuterol/salbutamol inhalation aerosol at the Screening Visit for use as needed for the duration of the study. The use of spacer devices with the metered dose inhaler (MDI) will not be allowed during the study with exception of it’s use during reversibility testing at the Screening Visit. Nebulized albuterol/salbutamol will not be allowed at any time during the study. Subjects must be able to withhold all inhaled short-acting ß2 sympathomimetic bronchodilators for at least 6 hours prior to all study visits.
9. If female, is currently not pregnant, breast feeding, or attempting to become pregnant, has a negative serum pregnancy test, and is of
• Non-childbearing potential, defined as:
- Before menarche, or
- =1 year post-menopausal, or
- Surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy), or
- Congenital sterility, or
- Diagnosed as infertile & not undergoing treatment to reverse infertility or is
1. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation &/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
2. Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks of the Screening Visit. In addition, the subject must be excluded if such infection occurs between the Screening Visit and the Randomization Visit.
3. Any asthma exacerbation requiring oral corticosteroids within 1 month of the Screening Visit. A subject must not have had an emergency room visit or hospitalization for asthma within 2 months prior to the Screening Visit.
4. Presence of glaucoma, cataracts, ocular herpes simplex, or malignancy other than basal cell carcinoma.
5. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular (e.g congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia or coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine (e.g uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison’s disease, Cushing’s syndrome), gastrointestinal (e.g poorly-controlled peptic ulcer, GERD), or pulmonary (e.g chronic bronchitis, emphysema, bronchiectasis with the need for treatment, cystic fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease).
6. Have any of the following conditions that, in the judgment of the investigator, might cause participation in this study to be detrimental to the subject, including, but not limited to:
• Current malignancy excluding basal cell carcinoma; History of malignancy is acceptable only if the subject has been in remission for 1 year prior to the Screening Visit.
• Current or untreated tuberculosis; History of tuberculosis is acceptable only if a subject has received an approved prophylactic treatment regimen or an approved active treatment regimen and has had no evidence of active disease for a minimum of 2 years
• Uncontrolled hypertension (systolic BP =160 or diastolic BP >100)
• Stroke within 3 months prior to the Screening Visit
• Immunologic compromise
7. History of a positive test for HIV, hepatitis B or hepatitis C infection.
8. Untreated oral candidiasis at the Screening Visit. Subjects with clinical visual evidence of oral candidiasis and who agree to receive treatment and comply with appropriate medical monitoring may enter the study.
9. History of any adverse reaction to any intranasal, inhaled or systemic corticosteroid therapy. Known/suspected sensitivity to the constituents of the dry powder inhalers used in the study (i.e lactose).
10. History of severe allergy to milk protein.
11. Use of systemic, oral or depot corticosteroids within 4 weeks prior to the Screening Visit
• Use of topical corticosteroids (=1% hydrocortisone cream) for dermatological disease is permitted
• Use of intranasal corticosteroids or ocular corticosteroids at a stable dose for at least 4 weeks prior to the Screening Visit and throughout the study is permitted
12. Use of immunosuppressive medications within 4 weeks prior to the Screening Visit and during the study.
13.Immunotherapy for the treatment of allergy at a stable maintenance dose for at least 90 days prior to the Screening Visit and which will remain at a stable dose without escalation throughout the study i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to evaluate the dose response, efficacy and safety of 4 different doses of fluticasone propionate (50, 100, 200, and 400mcg) delivered as Fluticasone Spiromax® Inhalation Powder (Fp Spiromax) when administered twice daily in subjects 12 years of age and older with severe persistent asthma who are uncontrolled on high dose ICS therapy.;Secondary Objective: ;Primary end point(s): The primary endpoint is:<br>• Change from baseline in trough (AM pre-dose and pre-rescue bronchodilator) FEV1 over the 12-week Treatment Period<br>;Timepoint(s) of evaluation of this end point: The primary endpoint is:<br>• Change from baseline in trough (AM pre-dose and pre-rescue bronchodilator) FEV1 over the 12-week Treatment Period
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary Efficacy Endpoint:<br>• Change from baseline in weekly average of daily trough (pre-dose and pre-rescue bronchodilator) AM PEF over the 12-week Treatment Period<br>• Change from baseline in weekly average of daily PM PEF over the 12-week Treatment Period<br>• Time to withdrawal due to meeting stopping criteria for worsening asthma during the 12-week Treatment Period<br>• Change from baseline in the percentage of rescue-free 24-hour periods during the 12-week Treatment Period<br>;Timepoint(s) of evaluation of this end point: • Change from baseline in weekly average of daily trough (pre-dose and pre-rescue bronchodilator) AM PEF over the 12-week Treatment Period<br>• Change from baseline in weekly average of daily PM PEF over the 12-week Treatment Period<br>•Time to withdrawal due to meeting stopping criteria for worsening asthma during the 12-week Treatment Period<br>• Change from baseline in the percentage of rescue-free 24-hour periods during the 12-week Treatment Period<br>