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A Study of the Effectiveness and Safety of Different Doses of Fluticasone Propionate Taken From a Dry Powder Inhaler (Puffer) in Adolescents and Adults Who Have Asthma That is Not Controlled by High Dose Inhaled Corticosteroid Asthma Medications

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01576718
Collaborator
(none)
889
Enrollment
300
Locations
6
Arms
18
Duration (Months)
3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
889 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A 12-Week Dose-ranging Study to Evaluate the Efficacy and Safety of Fp Spiromax® (Fluticasone Propionate Inhalation Powder) Administered Twice Daily Compared With Placebo in Adolescent and Adult Subjects With Severe Persistent Asthma Uncontrolled on High Dose Inhaled Corticosteroid Therapy
Study Start Date :
Apr 1, 2012
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Oct 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Fp MDPI 50 mcg

Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.

Drug: Fp MDPI
Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened. During the treatment period, participants were randomized to 50, 100, 200 or 400 mcg of Fp one inhalation twice a day for a total daily dose of 100, 200, 400 or 800 mcg. Study drug was administered in the morning and in the evening.
Other Names:
  • fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder

    • Drug: albuterol/salbutamol
    A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
    Other Names:
  • short-acting β2-adrenergic agonists

    		•
    Experimental: Fp MDPI 100 mcg

    Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.

    Drug: Fp MDPI
    Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened. During the treatment period, participants were randomized to 50, 100, 200 or 400 mcg of Fp one inhalation twice a day for a total daily dose of 100, 200, 400 or 800 mcg. Study drug was administered in the morning and in the evening.
    Other Names:
  • fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder

    • Drug: albuterol/salbutamol
    A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
    Other Names:
  • short-acting β2-adrenergic agonists

    		•
    Experimental: Fp MDPI 200 mcg

    Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.

    Drug: Fp MDPI
    Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened. During the treatment period, participants were randomized to 50, 100, 200 or 400 mcg of Fp one inhalation twice a day for a total daily dose of 100, 200, 400 or 800 mcg. Study drug was administered in the morning and in the evening.
    Other Names:
  • fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder

    • Drug: albuterol/salbutamol
    A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
    Other Names:
  • short-acting β2-adrenergic agonists

    		•
    Experimental: Fp MDPI 400 mcg

    Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.

    Drug: Fp MDPI
    Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened. During the treatment period, participants were randomized to 50, 100, 200 or 400 mcg of Fp one inhalation twice a day for a total daily dose of 100, 200, 400 or 800 mcg. Study drug was administered in the morning and in the evening.
    Other Names:
  • fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder

    • Drug: albuterol/salbutamol
    A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
    Other Names:
  • short-acting β2-adrenergic agonists

    		•
    Placebo Comparator: Placebo MDPI

    Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.

    Other: Placebo MDPI
    Placebo multidose dry powder inhaler (MDPI) in the morning and evening. Placebo MDPI was provided in devices identical in appearance to Fp MDPI.

    Drug: albuterol/salbutamol
    A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
    Other Names:
  • short-acting β2-adrenergic agonists

    		•
    Active Comparator: Flovent Diskus 250mcg

    Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.

    Drug: Flovent Diskus
    Flovent Diskus contains the active ingredient fluticasone propionate (Fp). Flovent Diskus 250 mcg was used twice a day, once in the morning and evening, for a total daily dose of 500 mcg of Fp. This therapy was not blinded as the inhaler device was different than the MDPI used in the other treatment arms.
    Other Names:
  • Fluticasone propionate

    • Drug: albuterol/salbutamol
    A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
    Other Names:
  • short-acting β2-adrenergic agonists

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period [Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

      Trough FEV1 was measured electronically by spirometry at morning (AM) investigational site visits, before administration of the AM dose of study drug, and before albuterol/salbutamol administration. The highest FEV1 value from 3 acceptable and 2 reproducible maneuvers was used. All FEV1 data were submitted to a central reading center for evaluation. The p-values for the treatment comparisons to placebo are from an MMRM model excluding FLOVENT DISKUS data: change from baseline = baseline FEV1 + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.

    Secondary Outcome Measures

    1. Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period [Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

      Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. On mornings for which a treatment visit was scheduled (TV1 through TV9), the PEF was measured and recorded at the investigational site visit. Baseline trough AM PEF was defined as the average of recorded (non-missing) trough AM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to placebo are from an MMRM model excluding FLOVENT DISKUS data: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.

    2. Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period [Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

      Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. PM PEF baseline was defined as the average of recorded (nonmissing) PM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to placebo are from an MMRM model excluding FLOVENT DISKUS data: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.

    3. The Kaplan-Meier Estimate Of The Probability Of Remaining In The Study At Week 12 [Day 1 to Week 12]

      The analysis of probability of remaining in the study at Week 12 used the time to patient withdrawal for worsening asthma. Worsening asthma was defined as: clinic visit FEV1 below the FEV1 stability limit value calculated on Day 1. any 7-day run-in or treatment window (using information from the patient diary) during which the subject experienced: 3 or more days in which the highest PEF has fallen below the PEF stability limit calculated on Day 1 3 or more days in which ≥12 inhalations/day of albuterol/salbutamol was used 2 or more days in which the subject experienced a nighttime asthma symptom score of >2 clinical asthma exacerbation, defined as worsening asthma requiring any treatment other than study drug or rescue albuterol/salbutamol including the use of systemic corticosteroids and/or ER visit or hospitalization. Patients who had withdrawn due to reasons other than worsening asthma were right-censored at the date of last assessment.

    4. Change From Baseline In The Percentage Of Rescue-Free 24-Hour Periods [Baseline (Day -6 to Day 1 predose), Treatment (Day 1 to Week 12)]

      The change from baseline in the percentage of rescue-free 24-hour periods was analyzed with a marginal (also called population averaged) logistic model, with the response being the proportion of rescue-free 24-hour periods. The model included 2 time points of measurement for each subject: the baseline (the last 7 days before the treatment period) and the treatment period. The model contained covariates for sex, age, and treatment. Rescue-free days were as indicated in patient diaries. Data values are estimated means.

    5. Area Under The Plasma Concentration-Time Curve From Time Zero To The Time Of The Last Measurable Concentration (AUC0-t) [Day 1 predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose]

    6. Maximum Observed Plasma Concentration (Cmax) [Day 1 predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose]

    7. Time Of Maximum Observed Plasma Concentration (Tmax) [Day 1 predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose]

    8. Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period [Day 1 to Week 12]

      An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

    9. Patients With Positive Swab Test Results for Oral Candidiasis [Screening (Days -21 to -14), Randomization (Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12]

      Oropharyngeal examinations for visual evidence of oral candidiasis were conducted at each visit. Any visual evidence of oral candidiasis during the oropharyngeal exam was evaluated by obtaining and analyzing a swab of the suspect area. This outcomes indicates how many patients had positive swab test results. The total number of patients who had oropharyngeal exams at each timepoint are specified in the timepoint field. Appropriate therapy was to be initiated immediately at the discretion of the investigator and was not to be delayed for culture confirmation. Subjects with a culture-positive infection could continue participation in the study on appropriate anti-infective therapy, provided this therapy was not prohibited by the protocol.

    10. 24-Hour Urinary Cortisol Excretion at Baseline, Week 12 and Endpoint [Baseline (Day 1), Week 12, Endpoint]

      24-hour urinary cortisol excretion was determined from 24-hour pooled-urine samples; urine was refrigerated until return to the investigational site after each 24-hour collection period. Urine was collected within 7 days of Day 1 and within 7 days of Week 12. Urine cortisol sample collection was not required at endpoint visit for subjects who terminated early from the study.

    Other Outcome Measures

    1. Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period (Including the Flovent Diskus Treatment Arm) [Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

      Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. On mornings for which a treatment visit was scheduled (TV1 through TV9), the PEF was measured and recorded at the investigational site visit. Baseline trough AM PEF was defined as the average of recorded (nonmissing) trough AM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to Flovent Diskus are from an MMRM model which includes data from all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.

    2. Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period (Including the Flovent Diskus Treatment Arm) [Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

      Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. On mornings for which a treatment visit was scheduled (TV1 through TV9), the PEF was measured and recorded at the investigational site visit. Baseline trough AM PEF was defined as the average of recorded (nonmissing) trough AM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to Flovent Diskus are from an MMRM model that included data for all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.

    3. Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period (Including the Flovent Diskus Treatment Arm) [Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

      Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. PM PEF baseline was defined as the average of recorded (nonmissing) PM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to Flovent Diskus are from an MMRM model that included data for all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Written informed consent/assent signed and dated by the subject and/or parent /legal guardian 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, and 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 (NIH).

    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. ATS/ERS 2005 criteria for acceptability, reproducibility, and end of test must be met for spirometry

    1. Reversibility of Disease: Demonstrated a ≥12% reversibility of FEV1 within 30 minutes following 2 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers are permitted for reversibility testing only) at the Screening Visit. If a subject fails to demonstrate an increase in FEV1 ≥12% then the subject is not eligible for the study and will not be allowed to re-screen. Reversibility values of 11.50 - 11.99 will be rounded to 12. Documented historical reversibility of ≥ 12 % within 3 months of the Screening Visit will be accepted.

    2. Current Asthma Therapy: Subjects will be required to be on a short acting β2 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 for four weeks prior to the Screening Visit at one of the following doses:

    • Fluticasone propionate HFA MDI ≥ 880 mcg/day

    • Fluticasone propionate DPI≥ 1000 mcg/day

    • Beclomethasone dipropionate DPI ≥ 2000 mcg/day

    • Beclomethasone dipropionate HFA (QVAR)≥ 640 mcg/day

    • Beclomethasone dipropionate HFA (Clenil Modulite)≥ 2000 mcg/day

    • Budesonide DPI ≥ 1600 mcg/day

    • Budesonide MDI ≥ 1600 mcg/day

    • Flunisolide ≥ 2000 mcg/day

    • Triamcinolone acetonide ≥ 2000 mcg /day

    • Mometasone furoate DPI ≥ 880 mcg/day

    • Ciclesonide HFA MDI ≥ 640 mcg/day

    Exception 1: Based upon the investigator's judgment that there is no inherent harm in changing the subject's current ICS/LABA therapy and the subject provides consent, subjects on inhaled Fluticasone propionate/salmeterol DPI ≥ 1000 mcg/day, or Fluticasone propionate/salmeterol HFA ≥ 880 mcg/day, or Fluticasone propionate/Formoterol ≥ 1000 mcg/day,or Beclomethasone dipropionate/Formoterol ≥ 400 mcg/day, or Budesonide/formoterol HFA ≥ 640 mcg/day, or Budesonide/formoterol DPI ≥ 800 mcg/day, or Mometasone furoate/formoterol MDI ≥ 800 mcg/day or subjects on a qualifying ICS dose plus a long-acting β2-agonists (LABA) administered via separate inhalers, may be switched to a qualifying dose of fluticasone propionate provided the subjects will not participate in the PK portion of the study.

    Exception 2: Subjects on a qualifying dose of fluticasone propionate who wish to participate in the PK portion of the study and who provide consent may have their fluticasone propionate switched to a different qualifying ICS (non-fluticasone propionate) at a pre-screening visit. The subject will be required to return to the clinic to complete the Screening Visit following a 1-week washout period.

    1. Short-Acting β2-Agonists: All subjects must be able to replace their current short-acting β2-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 β2 sympathomimetic bronchodilators for at least 6 hours prior to all study visits.

    2. 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 and not undergoing treatment to reverse infertility or is of

    • Child-bearing potential, willing to commit to using a consistent and acceptable method of birth control as defined below for the duration of the study:

    • Systemic contraception used for 1 month prior to screening, including birth control pills, transdermal patch (Ortho Evra®), vaginal ring (NuvaRing®), levonorgesterel (Norplant®), or injectable progesterone (Depo-Provera®), or

    • Double barrier methods (condoms, cervical cap, diaphragm, and vaginal contraceptive film with spermicide), or

    • Intrauterine device (IUD) or

    • Monogamous with a vasectomized male partner or is of

    • Child-bearing potential and not sexually active, willing to commit to using a consistent and acceptable method of birth control as defined above for the duration of the study, in the event the subject becomes sexually active

    1. Capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements (visits, record-keeping, etc).
    Exclusion Criteria:

    1. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation and/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 any hospitalization for asthma within 2 month prior to the Screening Visit.

    Note: An exacerbation of asthma is defined as any worsening of asthma requiring any treatment other than rescue albuterol/salbutamol HFA MDI and/or the subject's regular inhaled corticosteroid maintenance treatment. This includes requiring the use of systemic corticosteroids and/or emergency room visit or hospitalization, a change in the subject's regular inhaled corticosteroid maintenance treatment, or the addition of other asthma medications.

    1. Presence of glaucoma, cataracts, ocular herpes simplex, or malignancy other than basal cell carcinoma.

    2. 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). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

    3. 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 one year prior to the Screening Visit. (Remission is defined as no current evidence of malignancy and no treatment for the malignancy in the 12 months 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

    1. History of a positive test for HIV, hepatitis B or hepatitis C infection.

    2. 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

    3. History of any adverse reaction to any intranasal, inhaled or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the dry powder inhalers (Spiromax or Diskus) used in the study (i.e., lactose).

    4. History of severe allergy to milk protein.

    5. 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

    1. Use of immunosuppressive medications within 4 weeks prior to the Screening Visit and during the study.

    2. 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 is permitted.

    3. Use of Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, ketoconazole, itraconazole) within 4 weeks prior to the Screening Visit. Strong and moderate CYP3A4 inhibitors are prohibited and weak CYP3A4 are allowed.

    4. History of alcohol or drug abuse within two years preceding the Screening Visit.

    5. Current smoker or a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes/day for 1 year). A subject may not have used tobacco products within the past one year (e.g., cigarettes, cigars, chewing tobacco, or pipe tobacco).

    6. Study participation by clinical investigator site employees and/or their immediate relatives.

    7. Study participation by more than one subject from the same household at the same time. However, after the study completion or discontinuation by one subject another subject from the same household may be screened.

    8. Participation in any investigational drug study within the 30 days (starting at the final follow-up visit) preceding the Screening Visit or planned participation in another investigational drug study at any time during this study.

    9. Pregnancy, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study related visit (for eligible subjects only - if applicable). Eligible female subjects unwilling to employ appropriate contraceptive measures to ensure that pregnancy will not occur during the study will be excluded.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Teva Investigational Site 10504 Birmingham Alabama United States
    2 Teva Investigational Site 10565 Homewood Alabama United States
    3 Teva Investigational Site 11527 Goodyear Arizona United States
    4 Teva Investigational Site 10516 Tucson Arizona United States
    5 Teva Investigational Site 10573 Bakersfield California United States
    6 Teva Investigational Site 11518 Costa Mesa California United States
    7 Teva Investigational Site 10590 Fountain Valley California United States
    8 Teva Investigational Site 10551 Granada Hills California United States
    9 Teva Investigational Site 11520 Huntington Beach California United States
    10 Teva Investigational Site 11545 Huntington Beach California United States
    11 Teva Investigational Site 10547 Long Beach California United States
    12 Teva Investigational Site 11549 Los Angeles California United States
    13 Teva Investigational Site 10503 Mission Viejo California United States
    14 Teva Investigational Site 10536 Newport Beach California United States
    15 Teva Investigational Site 10540 Orange California United States
    16 Teva Investigational Site 11551 Orange California United States
    17 Teva Investigational Site 10578 Palmdale California United States
    18 Teva Investigational Site 10585 Redwood City California United States
    19 Teva Investigational Site 11538 Rolling Hills Estates California United States
    20 Teva Investigational Site 11522 Roseville California United States
    21 Teva Investigational Site 10582 San Diego California United States
    22 Teva Investigational Site 11554 San Diego California United States
    23 Teva Investigational Site 10563 San Jose California United States
    24 Teva Investigational Site 11556 Santa Monica California United States
    25 Teva Investigational Site 10506 Stockton California United States
    26 Teva Investigational Site 10529 Walnut Creek California United States
    27 Teva Investigational Site 10545 Centennial Colorado United States
    28 Teva Investigational Site 10572 Colorado Springs Colorado United States
    29 Teva Investigational Site 10533 Denver Colorado United States
    30 Teva Investigational Site 11531 Denver Colorado United States
    31 Teva Investigational Site 11542 Denver Colorado United States
    32 Teva Investigational Site 11569 Wheat Ridge Colorado United States
    33 Teva Investigational Site 10528 Waterbury Connecticut United States
    34 Teva Investigational Site 10556 Boynton Beach Florida United States
    35 Teva Investigational Site 11513 Brandon Florida United States
    36 Teva Investigational Site 11507 Clearwater Florida United States
    37 Teva Investigational Site 11546 Fort Myers Florida United States
    38 Teva Investigational Site 11526 Hialeah Florida United States
    39 Teva Investigational Site 11525 Kissimmee Florida United States
    40 Teva Investigational Site 10537 Miami Florida United States
    41 Teva Investigational Site 10553 Miami Florida United States
    42 Teva Investigational Site 11508 Miami Florida United States
    43 Teva Investigational Site 11514 Miami Florida United States
    44 Teva Investigational Site 11516 Miami Florida United States
    45 Teva Investigational Site 11530 Miami Florida United States
    46 Teva Investigational Site 11570 Miami Florida United States
    47 Teva Investigational Site 10571 Ocala Florida United States
    48 Teva Investigational Site 11537 Sarasota Florida United States
    49 Teva Investigational Site 10593 South Miami Florida United States
    50 Teva Investigational Site 11555 Tallahassee Florida United States
    51 Teva Investigational Site 10554 Tamarac Florida United States
    52 Teva Investigational Site 10539 Tampa Florida United States
    53 Teva Investigational Site 10525 Valrico Florida United States
    54 Teva Investigational Site 11504 Albany Georgia United States
    55 Teva Investigational Site 10511 Columbus Georgia United States
    56 Teva Investigational Site 11510 Columbus Georgia United States
    57 Teva Investigational Site 11572 Columbus Georgia United States
    58 Teva Investigational Site 10568 Lawrenceville Georgia United States
    59 Teva Investigational Site 10586 Lilburn Georgia United States
    60 Teva Investigational Site 11539 Savannah Georgia United States
    61 Teva Investigational Site 10543 Stockbridge Georgia United States
    62 Teva Investigational Site 11558 Indianapolis Indiana United States
    63 Teva Investigational Site 10527 South Bend Indiana United States
    64 Teva Investigational Site 10584 Iowa City Iowa United States
    65 Teva Investigational Site 11501 Overland Park Kansas United States
    66 Teva Investigational Site 10591 Lexington Kentucky United States
    67 Teva Investigational Site 11567 Louisville Kentucky United States
    68 Teva Investigational Site 10513 Metairie Louisiana United States
    69 Teva Investigational Site 10564 Bangor Maine United States
    70 Teva Investigational Site 11548 Baltimore Maryland United States
    71 Teva Investigational Site 10510 Largo Maryland United States
    72 Teva Investigational Site 10577 Wheaton Maryland United States
    73 Teva Investigational Site 10538 Brockton Massachusetts United States
    74 Teva Investigational Site 10546 North Dartmouth Massachusetts United States
    75 Teva Investigational Site 11502 Troy Michigan United States
    76 Teva Investigational Site 10531 Plymouth Minnesota United States
    77 Teva Investigational Site 11562 Columbia Missouri United States
    78 Teva Investigational Site 11563 Columbia Missouri United States
    79 Teva Investigational Site 10552 Saint Louis Missouri United States
    80 Teva Investigational Site 10575 Saint Louis Missouri United States
    81 Teva Investigational Site 10589 Saint Louis Missouri United States
    82 Teva Investigational Site 11532 Saint Louis Missouri United States
    83 Teva Investigational Site 10518 Bellevue Nebraska United States
    84 Teva Investigational Site 10550 Omaha Nebraska United States
    85 Teva Investigational Site 11529 Omaha Nebraska United States
    86 Teva Investigational Site 11571 Las Vegas Nevada United States
    87 Teva Investigational Site 10559 Cherry Hill New Jersey United States
    88 Teva Investigational Site 11566 Edison New Jersey United States
    89 Teva Investigational Site 10501 Hillsborough New Jersey United States
    90 Teva Investigational Site 11550 Ocean City New Jersey United States
    91 Teva Investigational Site 10588 West Orange New Jersey United States
    92 Teva Investigational Site 11503 Albuquerque New Mexico United States
    93 Teva Investigational Site 10580 Bronx New York United States
    94 Teva Investigational Site 10587 Brooklyn New York United States
    95 Teva Investigational Site 10520 New York New York United States
    96 Teva Investigational Site 10532 Newburgh New York United States
    97 Teva Investigational Site 10567 North Syracuse New York United States
    98 Teva Investigational Site 10512 Rochester New York United States
    99 Teva Investigational Site 10522 Canton Ohio United States
    100 Teva Investigational Site 10507 Cincinnati Ohio United States
    101 Teva Investigational Site 10523 Cincinnati Ohio United States
    102 Teva Investigational Site 10544 Columbus Ohio United States
    103 Teva Investigational Site 11521 Dayton Ohio United States
    104 Teva Investigational Site 11505 Middleburg Heights Ohio United States
    105 Teva Investigational Site 10560 Oklahoma City Oklahoma United States
    106 Teva Investigational Site 10574 Oklahoma City Oklahoma United States
    107 Teva Investigational Site 10579 Oklahoma City Oklahoma United States
    108 Teva Investigational Site 11544 Tulsa Oklahoma United States
    109 Teva Investigational Site 10598 Ashland Oregon United States
    110 Teva Investigational Site 11543 Medford Oregon United States
    111 Teva Investigational Site 11557 Portland Oregon United States
    112 Teva Investigational Site 10509 Altoona Pennsylvania United States
    113 Teva Investigational Site 10555 Philadelphia Pennsylvania United States
    114 Teva Investigational Site 10566 Pittsburgh Pennsylvania United States
    115 Teva Investigational Site 10521 Upland Pennsylvania United States
    116 Teva Investigational Site 10581 Lincoln Rhode Island United States
    117 Teva Investigational Site 10562 Providence Rhode Island United States
    118 Teva Investigational Site 10526 Charleston South Carolina United States
    119 Teva Investigational Site 11547 Charleston South Carolina United States
    120 Teva Investigational Site 10583 Orangeburg South Carolina United States
    121 Teva Investigational Site 10517 Spartanburg South Carolina United States
    122 Teva Investigational Site 11515 Spartanburg South Carolina United States
    123 Teva Investigational Site 10519 Boerne Texas United States
    124 Teva Investigational Site 10541 Dallas Texas United States
    125 Teva Investigational Site 10542 Dallas Texas United States
    126 Teva Investigational Site 10548 El Paso Texas United States
    127 Teva Investigational Site 11552 El Paso Texas United States
    128 Teva Investigational Site 11512 Fort Worth Texas United States
    129 Teva Investigational Site 11565 Houston Texas United States
    130 Teva Investigational Site 11568 Houston Texas United States
    131 Teva Investigational Site 10515 San Antonio Texas United States
    132 Teva Investigational Site 10569 San Antonio Texas United States
    133 Teva Investigational Site 11517 San Antonio Texas United States
    134 Teva Investigational Site 11519 San Antonio Texas United States
    135 Teva Investigational Site 11560 Waco Texas United States
    136 Teva Investigational Site 11528 Layton Utah United States
    137 Teva Investigational Site 10576 Provo Utah United States
    138 Teva Investigational Site 10534 South Burlington Vermont United States
    139 Teva Investigational Site 10502 Fairfax Virginia United States
    140 Teva Investigational Site 10595 Manassas Virginia United States
    141 Teva Investigational Site 10508 Richmond Virginia United States
    142 Teva Investigational Site 11561 Bellingham Washington United States
    143 Teva Investigational Site 11541 Seattle Washington United States
    144 Teva Investigational Site 10524 Spokane Washington United States
    145 Teva Investigational Site 10530 Tacoma Washington United States
    146 Teva Investigational Site 11511 Tacoma Washington United States
    147 Teva Investigational Site 10570 Greenfield Wisconsin United States
    148 Teva Investigational Site 11559 Greenfield Wisconsin United States
    149 Teva Investigational Site 85570 Bedford Park Australia
    150 Teva Investigational Site 85571 Parkville Australia
    151 Teva Investigational Site 59507 Burgas Bulgaria
    152 Teva Investigational Site 59503 Lovech Bulgaria
    153 Teva Investigational Site 59506 Pleven Bulgaria
    154 Teva Investigational Site 59504 Ruse Bulgaria
    155 Teva Investigational Site 59501 Sofia Bulgaria
    156 Teva Investigational Site 59502 Sofia Bulgaria
    157 Teva Investigational Site 59505 Sofia Bulgaria
    158 Teva Investigational Site 59508 Sofia Bulgaria
    159 Teva Investigational Site 59509 Varna Bulgaria
    160 Teva Investigational Site 11594 Burlington Ontario Canada
    161 Teva Investigational Site 11595 Etobicoke Ontario Canada
    162 Teva Investigational Site 11592 Sarnia Ontario Canada
    163 Teva Investigational Site 11590 Toronto Ontario Canada
    164 Teva Investigational Site 11591 Newmarket Canada
    165 Teva Investigational Site 85501 Zagreb Croatia
    166 Teva Investigational Site 85502 Zagreb Croatia
    167 Teva Investigational Site 85503 Zagreb Croatia
    168 Teva Investigational Site 85504 Zagreb Croatia
    169 Teva Investigational Site 70561 Berlin Germany
    170 Teva Investigational Site 70564 Bonn Germany
    171 Teva Investigational Site 70557 Cottbus Germany
    172 Teva Investigational Site 70553 Delitzsch Germany
    173 Teva Investigational Site 70558 Frankfurt Germany
    174 Teva Investigational Site 70562 Hamburg Germany
    175 Teva Investigational Site 70560 Hanover Germany
    176 Teva Investigational Site 70555 Leipzig Germany
    177 Teva Investigational Site 70556 Magdeburg Germany
    178 Teva Investigational Site 70550 Munchen Germany
    179 Teva Investigational Site 70554 Munchen Germany
    180 Teva Investigational Site 70552 Munster Germany
    181 Teva Investigational Site 70563 Nurnberg Germany
    182 Teva Investigational Site 70551 Rudersdorf Germany
    183 Teva Investigational Site 70559 Wiesbaden Germany
    184 Teva Investigational Site 85533 Athens Greece
    185 Teva Investigational Site 85534 Athens Greece
    186 Teva Investigational Site 85531 Heraklion Greece
    187 Teva Investigational Site 85532 Larissa Greece
    188 Teva Investigational Site 85530 Thessaloniki Greece
    189 Teva Investigational Site 36507 Balassagyarmat Hungary
    190 Teva Investigational Site 36504 Budapest Hungary
    191 Teva Investigational Site 36505 Budapest Hungary
    192 Teva Investigational Site 36514 Csoma Hungary
    193 Teva Investigational Site 36516 Erd Hungary
    194 Teva Investigational Site 36513 Kaba Hungary
    195 Teva Investigational Site 36515 Kaposvar Hungary
    196 Teva Investigational Site 36503 Miskolc Hungary
    197 Teva Investigational Site 36502 Nyiregyhaza Hungary
    198 Teva Investigational Site 36510 Siofok Hungary
    199 Teva Investigational Site 36517 Szarvas Hungary
    200 Teva Investigational Site 36508 Szazhalombatta Hungary
    201 Teva Investigational Site 36506 Szeged Hungary
    202 Teva Investigational Site 36509 Szeged Hungary
    203 Teva Investigational Site 36501 Szombathely Hungary
    204 Teva Investigational Site 36512 Veszprem Hungary
    205 Teva Investigational Site 59550 Dublin Ireland
    206 Teva Investigational Site 59551 Dublin Ireland
    207 Teva Investigational Site 72511 Ashkelon Israel
    208 Teva Investigational Site 72501 Haifa Israel
    209 Teva Investigational Site 72512 Haifa Israel
    210 Teva Investigational Site 72502 Jerusalem Israel
    211 Teva Investigational Site 72504 Jerusalem Israel
    212 Teva Investigational Site 72509 Kfar Saba Israel
    213 Teva Investigational Site 72506 Petach Tikva Israel
    214 Teva Investigational Site 72507 Ramat-Gan Israel
    215 Teva Investigational Site 72503 Rehovot Israel
    216 Teva Investigational Site 72510 Tel Aviv Israel
    217 Teva Investigational Site 72508 Tel-Aviv Israel
    218 Teva Investigational Site 72505 Zerifin Israel
    219 Teva Investigational Site 81571 Auckland New Zealand
    220 Teva Investigational Site 81572 Christchurch New Zealand
    221 Teva Investigational Site 81573 Tauranga New Zealand
    222 Teva Investigational Site 81570 Wellington New Zealand
    223 Teva Investigational Site 48507 Bialystok Poland
    224 Teva Investigational Site 48505 Bydgoszcz Poland
    225 Teva Investigational Site 48506 Grodzisk Mazowiecki Poland
    226 Teva Investigational Site 48501 Lodz Poland
    227 Teva Investigational Site 48509 Lodz Poland
    228 Teva Investigational Site 48513 Lublin Poland
    229 Teva Investigational Site 48508 Poznan Poland
    230 Teva Investigational Site 48512 Poznan Poland
    231 Teva Investigational Site 48502 Strzelce Opolskie Poland
    232 Teva Investigational Site 48503 Tarnow Poland
    233 Teva Investigational Site 48504 Wroclaw Poland
    234 Teva Investigational Site 81534 Brasov Romania
    235 Teva Investigational Site 81539 Brasov Romania
    236 Teva Investigational Site 81533 Bucharest Romania
    237 Teva Investigational Site 81535 Bucharest Romania
    238 Teva Investigational Site 81537 Bucharest Romania
    239 Teva Investigational Site 81531 Cluj-Napoca Romania
    240 Teva Investigational Site 81536 Cluj-Napoca Romania
    241 Teva Investigational Site 81530 Targu Mures Romania
    242 Teva Investigational Site 81532 Timisoara Romania
    243 Teva Investigational Site 81538 Timisoara Romania
    244 Teva Investigational Site 70505 Barnaul Russian Federation
    245 Teva Investigational Site 70502 Kazan Russian Federation
    246 Teva Investigational Site 70511 Moscow Russian Federation
    247 Teva Investigational Site 70512 Moscow Russian Federation
    248 Teva Investigational Site 70508 Ryazan Russian Federation
    249 Teva Investigational Site 70509 Samara Russian Federation
    250 Teva Investigational Site 70507 Smolensk Russian Federation
    251 Teva Investigational Site 70501 St. Petersburg Russian Federation
    252 Teva Investigational Site 70504 St. Petersburg Russian Federation
    253 Teva Investigational Site 70510 St. Petersburg Russian Federation
    254 Teva Investigational Site 70506 Tomsk Russian Federation
    255 Teva Investigational Site 70503 Yaroslavl Russian Federation
    256 Teva Investigational Site 81501 Belgrade Serbia
    257 Teva Investigational Site 36551 Bloemfontein South Africa
    258 Teva Investigational Site 36552 Cape Town South Africa
    259 Teva Investigational Site 36555 Cape Town South Africa
    260 Teva Investigational Site 36550 Port Elizabeth South Africa
    261 Teva Investigational Site 36553 Thabazimbi South Africa
    262 Teva Investigational Site 36554 Witbank South Africa
    263 Teva Investigational Site 34507 Aranjuez Spain
    264 Teva Investigational Site 34501 Badalona Spain
    265 Teva Investigational Site 34502 Barcelona Spain
    266 Teva Investigational Site 34510 Barcelona Spain
    267 Teva Investigational Site 34509 Bilbao Spain
    268 Teva Investigational Site 34506 Lleida Spain
    269 Teva Investigational Site 34505 Madrid Spain
    270 Teva Investigational Site 34503 Salt Spain
    271 Teva Investigational Site 34504 Santiago de Compostela Spain
    272 Teva Investigational Site 34508 Valencia Spain
    273 Teva Investigational Site 34511 Vitoria Spain
    274 Teva Investigational Site 80501 Dnipropetrovsk Ukraine
    275 Teva Investigational Site 80513 Dnipropetrovsk Ukraine
    276 Teva Investigational Site 80511 Donetsk Ukraine
    277 Teva Investigational Site 80502 Kharkiv Ukraine
    278 Teva Investigational Site 80503 Kharkiv Ukraine
    279 Teva Investigational Site 80504 Kyiv Ukraine
    280 Teva Investigational Site 80505 Kyiv Ukraine
    281 Teva Investigational Site 80506 Kyiv Ukraine
    282 Teva Investigational Site 80507 Kyiv Ukraine
    283 Teva Investigational Site 80508 Kyiv Ukraine
    284 Teva Investigational Site 80509 Kyiv Ukraine
    285 Teva Investigational Site 80517 Kyiv Ukraine
    286 Teva Investigational Site 80519 Kyiv Ukraine
    287 Teva Investigational Site 80520 Kyiv Ukraine
    288 Teva Investigational Site 80521 Kyiv Ukraine
    289 Teva Investigational Site 80514 Odesa Ukraine
    290 Teva Investigational Site 80516 Simferopol Ukraine
    291 Teva Investigational Site 80512 Vinnytsya Ukraine
    292 Teva Investigational Site 80515 Yalta Ukraine
    293 Teva Investigational Site 80522 Zaporizhia Ukraine
    294 Teva Investigational Site 80510 Zaporizhzhia Ukraine
    295 Teva Investigational Site 80518 Zaporizhzhya Ukraine
    296 Teva Investigational Site 34582 Cottingham United Kingdom
    297 Teva Investigational Site 34584 London United Kingdom
    298 Teva Investigational Site 34585 Penzance United Kingdom
    299 Teva Investigational Site 34580 Torpoint United Kingdom
    300 Teva Investigational Site 34581 Watford United Kingdom

    Sponsors and Collaborators

    • Teva Branded Pharmaceutical Products R&D, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT01576718
    Other Study ID Numbers:
    • FpS-AS-202
    • 2010-023601-35
    First Posted:
    Apr 12, 2012
    Last Update Posted:
    May 8, 2018
    Last Verified:
    May 1, 2018
    Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.
    Dose ranging
    Fluticasone Propionate
    Dry Powder Inhaler (DPI)
    High Dose ICS
    Asthma
    Additional relevant MeSH terms:
    Asthma
    Fluticasone
    Xhance
    Albuterol
    Adrenergic Agonists

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 1238 subjects with asthma at 180 centers were screened for enrollment. 889 subjects met entry criteria and were enrolled into the run-in period of the study. Of the 349 subjects who were not enrolled, 337 were excluded on the basis of inclusion/exclusion criteria, 5 subjects withdrew consent, and for 6 the reason given was "other".
    Arm/Group Title Placebo MDPI (Run-In) Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Upon enrollment, participants used current asthma medications and 1 inhalation of placebo multidose dry powder inhaler (MDPI), single-blind, twice daily for 14-day (±2 days). Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Period Title: Pre-Assignment Period (Run-In Placebo)
    STARTED 889 0 0 0 0 0 0
    COMPLETED 640 0 0 0 0 0 0
    NOT COMPLETED 249 0 0 0 0 0 0
    Period Title: Pre-Assignment Period (Run-In Placebo)
    STARTED 0 107 107 106 107 106 107
    Safety Population 0 107 107 106 107 106 106
    Efficacy Population (Full Analysis Set) 0 107 106 102 107 105 103
    COMPLETED 0 82 87 75 80 58 77
    NOT COMPLETED 0 25 20 31 27 48 30

    Baseline Characteristics

    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg Total
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Total of all reporting groups
    Overall Participants 107 107 106 107 106 107 640
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    47.9
    (14.59)
    48.7
    (12.48)
    47.7
    (14.18)
    50.9
    (13.32)
    49.8
    (12.87)
    49.2
    (13.26)
    49.0
    (13.46)
    Age, Customized (participants) [Number]
    Adolescents (12-17 years)
    2
    1.9%
    3
    2.8%
    1
    0.9%
    1
    0.9%
    1
    0.9%
    1
    0.9%
    9
    1.4%
    Adults (18-64 years)
    94
    87.9%
    99
    92.5%
    90
    84.9%
    90
    84.1%
    94
    88.7%
    96
    89.7%
    563
    88%
    Adults (65-84 years)
    11
    10.3%
    5
    4.7%
    15
    14.2%
    16
    15%
    11
    10.4%
    10
    9.3%
    68
    10.6%
    Sex: Female, Male (Count of Participants)
    Female
    63
    58.9%
    55
    51.4%
    66
    62.3%
    72
    67.3%
    65
    61.3%
    58
    54.2%
    379
    59.2%
    Male
    44
    41.1%
    52
    48.6%
    40
    37.7%
    35
    32.7%
    41
    38.7%
    49
    45.8%
    261
    40.8%
    Race/Ethnicity, Customized (participants) [Number]
    White
    96
    89.7%
    94
    87.9%
    93
    87.7%
    91
    85%
    96
    90.6%
    95
    88.8%
    565
    88.3%
    Black
    9
    8.4%
    12
    11.2%
    12
    11.3%
    13
    12.1%
    8
    7.5%
    11
    10.3%
    65
    10.2%
    Asian
    1
    0.9%
    1
    0.9%
    1
    0.9%
    2
    1.9%
    2
    1.9%
    0
    0%
    7
    1.1%
    American Indian or Alaskan Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    1
    0.2%
    Pacific Islander
    1
    0.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Other
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    1
    0.2%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    5
    4.7%
    7
    6.5%
    8
    7.5%
    12
    11.2%
    6
    5.7%
    9
    8.4%
    47
    7.3%
    Not Hispanic or Latino
    102
    95.3%
    100
    93.5%
    98
    92.5%
    95
    88.8%
    100
    94.3%
    98
    91.6%
    593
    92.7%
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    86.7
    (23.73)
    86.6
    (22.90)
    84.4
    (21.89)
    84.4
    (20.56)
    86.2
    (25.19)
    83.3
    (16.76)
    85.3
    (21.95)
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    169.4
    (13.04)
    168.7
    (9.14)
    168.4
    (7.86)
    167.4
    (9.67)
    168.1
    (8.57)
    168.0
    (8.33)
    168.3
    (9.58)
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    31.3
    (17.88)
    30.4
    (7.60)
    29.8
    (8.12)
    30.1
    (6.81)
    30.5
    (8.83)
    29.6
    (6.03)
    30.3
    (10.02)
    Forced Expiratory Volume in 1 Second (FEV1) (liters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [liters]
    2.108
    (0.662)
    2.031
    (0.551)
    1.999
    (0.525)
    2.016
    (0.636)
    1.984
    (0.565)
    1.955
    (0.529)
    2.016
    (0.579)
    % Predicted Expiratory Volume In 1 Second (percent predicted FEV1) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percent predicted FEV1]
    63.7
    (10.9)
    63.1
    (9.5)
    63.4
    (12.1)
    65.3
    (11.4)
    63.1
    (10.0)
    62.5
    (12.1)
    63.5
    (11.0)
    Qualifying Airway Reversibility (percentage increase in FEV1) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage increase in FEV1]
    31.6
    (22.4)
    27.3
    (14.7)
    30.4
    (25.2)
    29.1
    (19.5)
    28.9
    (19.1)
    26.8
    (15.7)
    29.0
    (19.8)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period
    Description Trough FEV1 was measured electronically by spirometry at morning (AM) investigational site visits, before administration of the AM dose of study drug, and before albuterol/salbutamol administration. The highest FEV1 value from 3 acceptable and 2 reproducible maneuvers was used. All FEV1 data were submitted to a central reading center for evaluation. The p-values for the treatment comparisons to placebo are from an MMRM model excluding FLOVENT DISKUS data: change from baseline = baseline FEV1 + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
    Time Frame Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set, including participants who contributed at least once to the analysis. Based on blinded data review, data from one site are excluded due to good clinical practice (GCP) concerns. Flovent Diskus data was used for confirmatory and exploratory endpoints; FEV1 data for Flovent Diskus is reported in outcome #12.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 104 102 97 103 98 0
    Least Squares Mean (Standard Error) [liters]
    0.059
    (0.0269)
    0.101
    (0.0268)
    0.109
    (0.0278)
    0.125
    (0.0274)
    0.053
    (0.0283)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Fp MDPI 100 mcg, Fp MDPI 200 mcg, Fp MDPI 400 mcg, Placebo MDPI
    Comments A linear in log-dose trend contrast was constructed to evaluate the time-averaged dose-response trend, where the logarithm of dose was defined as log(dose+1) to accommodate the case of a zero dose (placebo). A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 0.05 level. Specifically, the 2-sided linear in log-dose time-averaged trend test was first performed at the 0.05 level of significance.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0604
    Comments If the Fp MDPI showed a significantly positive trend, then contrasts for pairwise comparisons of each Fp MDPI dose versus placebo were done in the sequence of highest to lowest Fp MDPI dose.
    Method Regression, Linear
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0637
    Comments Significance at the 0.05 level.
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.072
    Confidence Interval (2-Sided) 95%
    -0.004 to 0.149
    Parameter Dispersion Type:
    Value:
    Estimation Comments Fp 400 - Placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1585
    Comments Significance at the 0.05 level
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.056
    Confidence Interval (2-Sided) 95%
    -0.022 to 0.133
    Parameter Dispersion Type:
    Value:
    Estimation Comments Fp 200 - Placebo
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2221
    Comments Significance at the 0.05 level
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.048
    Confidence Interval (2-Sided) 95%
    -0.029 to 0.124
    Parameter Dispersion Type:
    Value:
    Estimation Comments Fp 100 - Placebo
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value =0.8694
    Comments Significance at the 0.05 level
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.006
    Confidence Interval (2-Sided) 95%
    -0.070 to 0.083
    Parameter Dispersion Type:
    Value:
    Estimation Comments Fp 50 - Placebo
    2. Secondary Outcome
    Title Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period
    Description Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. On mornings for which a treatment visit was scheduled (TV1 through TV9), the PEF was measured and recorded at the investigational site visit. Baseline trough AM PEF was defined as the average of recorded (non-missing) trough AM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to placebo are from an MMRM model excluding FLOVENT DISKUS data: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
    Time Frame Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set, including participants who contributed at least once to the analysis. Based on blinded data review, data from one site are excluded due to good clinical practice (GCP) concerns. Flovent Diskus data was used for confirmatory and exploratory endpoints; morning PEF data for Flovent Diskus is reported in outcome #13.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 101 101 96 101 98 0
    Least Squares Mean (Standard Error) [liters/minute]
    10.48
    (4.299)
    9.34
    (4.245)
    10.03
    (4.420)
    9.61
    (4.307)
    2.24
    (4.507)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Fp MDPI 100 mcg, Fp MDPI 200 mcg, Fp MDPI 400 mcg, Placebo MDPI, Flovent Diskus 250mcg
    Comments A linear in log-dose trend contrast was constructed to evaluate the time-averaged dose-response trend, where the logarithm of dose was defined as log(dose+1) to accommodate the case of a zero dose (placebo). A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 0.05 level. Specifically, the 2-sided linear in log-dose time-averaged trend test was first performed at the 0.05 level of significance.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1512
    Comments If the Fp MDPI showed a significantly positive trend, then contrasts for pairwise comparisons of each Fp MDPI dose versus placebo were done in the sequence of highest to lowest Fp MDPI dose.
    Method Regression, Linear
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2361
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 7.36
    Confidence Interval (2-Sided) 95%
    -4.83 to 19.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2169
    Comments
    Method Regression, Linear
    Comments Significance at the 0.05 level
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 7.78
    Confidence Interval (2-Sided) 95%
    -4.59 to 20.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2523
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 7.09
    Confidence Interval (2-Sided) 95%
    -5.07 to 19.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1858
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 8.23
    Confidence Interval (2-Sided) 95%
    -3.98 to 20.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period
    Description Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. PM PEF baseline was defined as the average of recorded (nonmissing) PM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to placebo are from an MMRM model excluding FLOVENT DISKUS data: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
    Time Frame Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set, including participants who contributed at least once to the analysis. Based on blinded data review, data from one site are excluded due to good clinical practice (GCP) concerns. Flovent Diskus data was used for confirmatory and exploratory endpoints; evening PEF data for Flovent Diskus is reported in outcome #14.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 103 99 96 102 96 0
    Least Squares Mean (Standard Error) [liters/minute]
    3.81
    (4.183)
    6.41
    (4.209)
    7.45
    (4.335)
    10.97
    (4.208)
    3.42
    (4.462)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Fp MDPI 100 mcg, Fp MDPI 200 mcg, Fp MDPI 400 mcg, Placebo MDPI
    Comments A linear in log-dose trend contrast was constructed to evaluate the time-averaged dose-response trend, where the logarithm of dose was defined as log(dose+1) to accommodate the case of a zero dose (placebo). A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 0.05 level. Specifically, the 2-sided linear in log-dose time-averaged trend test was first performed at the 0.05 level of significance.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2879
    Comments If the Fp MDPI showed a significantly positive trend, then contrasts for pairwise comparisons of each Fp MDPI dose versus placebo were done in the sequence of highest to lowest Fp MDPI dose.
    Method Regression, Linear
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2166
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 7.56
    Confidence Interval (2-Sided) 95%
    -4.45 to 19.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5167
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 4.03
    Confidence Interval (2-Sided) 95%
    -8.17 to 16.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6258
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 2.99
    Confidence Interval (2-Sided) 95%
    -9.06 to 15.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
    Comments No explicit structure was assumed for the covariance among the repeated measures. Analyses for comparison of Fp MDPI to placebo did not contain FLOVENT DISKUS data.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9487
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.39
    Confidence Interval (2-Sided) 95%
    -11.60 to 12.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title The Kaplan-Meier Estimate Of The Probability Of Remaining In The Study At Week 12
    Description The analysis of probability of remaining in the study at Week 12 used the time to patient withdrawal for worsening asthma. Worsening asthma was defined as: clinic visit FEV1 below the FEV1 stability limit value calculated on Day 1. any 7-day run-in or treatment window (using information from the patient diary) during which the subject experienced: 3 or more days in which the highest PEF has fallen below the PEF stability limit calculated on Day 1 3 or more days in which ≥12 inhalations/day of albuterol/salbutamol was used 2 or more days in which the subject experienced a nighttime asthma symptom score of >2 clinical asthma exacerbation, defined as worsening asthma requiring any treatment other than study drug or rescue albuterol/salbutamol including the use of systemic corticosteroids and/or ER visit or hospitalization. Patients who had withdrawn due to reasons other than worsening asthma were right-censored at the date of last assessment.
    Time Frame Day 1 to Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 107 106 102 107 105 103
    Number (95% Confidence Interval) [probability]
    0.6872
    0.6330
    0.5852
    0.6109
    0.4722
    0.5657
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Placebo MDPI
    Comments P-value for comparison of survival curve to placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0341
    Comments Significance level of 0.05.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Placebo MDPI
    Comments P-value for comparison of survival curve to placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0340
    Comments Significance level of 0.05.
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
    Comments P-value for comparison of survival curve to placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0058
    Comments Significance level of 0.05.
    Method Log Rank
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
    Comments P-value for comparison of survival curve to placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0018
    Comments Significance level of 0.05.
    Method Log Rank
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Flovent Diskus 250mcg
    Comments P-value for comparison of survival curve to placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1006
    Comments Significance level of 0.05.
    Method Log Rank
    Comments
    5. Secondary Outcome
    Title Change From Baseline In The Percentage Of Rescue-Free 24-Hour Periods
    Description The change from baseline in the percentage of rescue-free 24-hour periods was analyzed with a marginal (also called population averaged) logistic model, with the response being the proportion of rescue-free 24-hour periods. The model included 2 time points of measurement for each subject: the baseline (the last 7 days before the treatment period) and the treatment period. The model contained covariates for sex, age, and treatment. Rescue-free days were as indicated in patient diaries. Data values are estimated means.
    Time Frame Baseline (Day -6 to Day 1 predose), Treatment (Day 1 to Week 12)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including participants who contributed at least once to the analysis.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 96 90 91 99 93 95
    Mean (Standard Error) [percentage of total 24 hour periods]
    22.78
    (4.016)
    26.41
    (4.013)
    16.18
    (3.662)
    28.05
    (3.951)
    27.15
    (4.475)
    15.87
    (3.750)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Placebo MDPI
    Comments Estimates computed from a generalized linear logistic model with gender and age as covariates and allows correlation between estimates on the same subject. Interpretation of the estimates is that they are the average over the population at the average level of continuous covariate (age) averaged over discrete covariate (gender).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.88116
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    -11.12 to 12.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Placebo MDPI
    Comments Estimates computed from a generalized linear logistic model with gender and age as covariates and allows correlation between estimates on the same subject. Interpretation of the estimates is that they are the average over the population at the average level of continuous covariate (age) averaged over discrete covariate (gender).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.05977
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.98
    Confidence Interval (2-Sided) 95%
    -22.64 to 0.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
    Comments Estimates computed from a generalized linear logistic model with gender and age as covariates and allows correlation between estimates on the same subject. Interpretation of the estimates is that they are the average over the population at the average level of continuous covariate (age) averaged over discrete covariate (gender).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.90426
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.74
    Confidence Interval (2-Sided) 95%
    -13.02 to 11.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
    Comments Estimates computed from a generalized linear logistic model with gender and age as covariates and allows correlation between estimates on the same subject. Interpretation of the estimates is that they are the average over the population at the average level of continuous covariate (age) averaged over discrete covariate (gender).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.47310
    Comments Significance at the 0.05 level
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.38
    Confidence Interval (2-Sided) 95%
    -16.57 to 7.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Area Under The Plasma Concentration-Time Curve From Time Zero To The Time Of The Last Measurable Concentration (AUC0-t)
    Description
    Time Frame Day 1 predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Two participants in the Fp MDPI 100 mcg treatment arm did not have AUC data. PK tests not run on participants in the Placebo MDPI arm.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 18 16 18 20 0 16
    Mean (Standard Deviation) [pg*hr/mL]
    117.6
    (145.79)
    126.8
    (33.73)
    292.0
    (162.28)
    462.8
    (262.45)
    162.3
    (74.79)
    7. Secondary Outcome
    Title Maximum Observed Plasma Concentration (Cmax)
    Description
    Time Frame Day 1 predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Two participants in the Fp MDPI 100 mcg treatment arm did not have AUC data. PK tests not run on participants in the Placebo MDPI arm.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 18 16 18 20 0 16
    Mean (Standard Deviation) [pg/mL]
    19.1
    (15.53)
    26.5
    (6.16)
    55.2
    (29.12)
    83.0
    (44.32)
    32.5
    (13.92)
    8. Secondary Outcome
    Title Time Of Maximum Observed Plasma Concentration (Tmax)
    Description
    Time Frame Day 1 predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Two participants in the Fp MDPI 100 mcg treatment arm did not have AUC data. PK tests not run on participants in the Placebo MDPI arm.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 18 16 18 20 0 16
    Mean (Standard Deviation) [hours]
    1.0
    (0.54)
    1.2
    (1.85)
    2.2
    (3.58)
    1.4
    (2.60)
    1.8
    (2.75)
    9. Secondary Outcome
    Title Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
    Description An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
    Time Frame Day 1 to Week 12

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 107 107 106 107 106 106
    Any adverse event (AE)
    31
    29%
    27
    25.2%
    34
    32.1%
    41
    38.3%
    33
    31.1%
    27
    25.2%
    Severe AE
    3
    2.8%
    1
    0.9%
    1
    0.9%
    1
    0.9%
    1
    0.9%
    0
    0%
    Treatment-related AE
    4
    3.7%
    1
    0.9%
    6
    5.7%
    9
    8.4%
    5
    4.7%
    2
    1.9%
    Deaths
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Other serious AEs
    1
    0.9%
    1
    0.9%
    1
    0.9%
    0
    0%
    1
    0.9%
    0
    0%
    Withdrawn from treatment due to AEs
    1
    0.9%
    1
    0.9%
    1
    0.9%
    1
    0.9%
    1
    0.9%
    0
    0%
    10. Secondary Outcome
    Title Patients With Positive Swab Test Results for Oral Candidiasis
    Description Oropharyngeal examinations for visual evidence of oral candidiasis were conducted at each visit. Any visual evidence of oral candidiasis during the oropharyngeal exam was evaluated by obtaining and analyzing a swab of the suspect area. This outcomes indicates how many patients had positive swab test results. The total number of patients who had oropharyngeal exams at each timepoint are specified in the timepoint field. Appropriate therapy was to be initiated immediately at the discretion of the investigator and was not to be delayed for culture confirmation. Subjects with a culture-positive infection could continue participation in the study on appropriate anti-infective therapy, provided this therapy was not prohibited by the protocol.
    Time Frame Screening (Days -21 to -14), Randomization (Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 107 107 106 107 106 106
    Screening
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Day 1
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.9%
    1
    0.9%
    Week 1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    1
    0.9%
    Week 2
    0
    0%
    0
    0%
    1
    0.9%
    2
    1.9%
    0
    0%
    0
    0%
    Week 3
    0
    0%
    0
    0%
    0
    0%
    4
    3.7%
    0
    0%
    0
    0%
    Week 4
    1
    0.9%
    0
    0%
    1
    0.9%
    1
    0.9%
    0
    0%
    0
    0%
    Week 6
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    Week 8
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    1
    0.9%
    Week 10
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    Week 12
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.9%
    11. Secondary Outcome
    Title 24-Hour Urinary Cortisol Excretion at Baseline, Week 12 and Endpoint
    Description 24-hour urinary cortisol excretion was determined from 24-hour pooled-urine samples; urine was refrigerated until return to the investigational site after each 24-hour collection period. Urine was collected within 7 days of Day 1 and within 7 days of Week 12. Urine cortisol sample collection was not required at endpoint visit for subjects who terminated early from the study.
    Time Frame Baseline (Day 1), Week 12, Endpoint

    Outcome Measure Data

    Analysis Population Description
    Urine cortisol analysis set
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 62 70 55 68 41 59
    Baseline
    65.3
    (42.69)
    63.8
    (44.70)
    66.6
    (45.53)
    57.4
    (34.68)
    74.3
    (43.54)
    66.2
    (42.68)
    Week 12
    71.8
    (48.37)
    61.5
    (45.73)
    66.8
    (53.96)
    46.2
    (38.67)
    69.2
    (49.56)
    58.5
    (43.75)
    Endpoint
    71.0
    (48.31)
    61.5
    (45.73)
    65.8
    (53.33)
    45.0
    (38.33)
    74.4
    (54.97)
    58.4
    (43.49)
    12. Other Pre-specified Outcome
    Title Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period (Including the Flovent Diskus Treatment Arm)
    Description Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. On mornings for which a treatment visit was scheduled (TV1 through TV9), the PEF was measured and recorded at the investigational site visit. Baseline trough AM PEF was defined as the average of recorded (nonmissing) trough AM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to Flovent Diskus are from an MMRM model which includes data from all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
    Time Frame Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set, including participants who contributed at least once to the analysis. Based on blinded data review, data from one site are excluded due to good clinical practice (GCP) concerns.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 104 102 97 103 98 100
    Least Squares Mean (Standard Error) [liters]
    0.063
    (0.027)
    0.102
    (0.0269)
    0.113
    (0.0279)
    0.129
    (0.0274)
    0.057
    (0.0284)
    0.110
    (0.0274)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value =0.6161
    Comments 0.05 level of significance.
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.019
    Confidence Interval (2-Sided) 95%
    -0.057 to 0.096
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9245
    Comments 0.05 level of significance.
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.004
    Confidence Interval (2-Sided) 95%
    -0.973 to 0.080
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8434
    Comments 0.05 level of significance.
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.008
    Confidence Interval (2-Sided) 95%
    -0.083 to 0.068
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2241
    Comments 0.05 level of significance.
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.047
    Confidence Interval (2-Sided) 95%
    -0.122 to 0.029
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1822
    Comments 0.05 level of significance.
    Method mixed model for repeated measures
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.053
    Confidence Interval (2-Sided) 95%
    -0.130 to 0.025
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Other Pre-specified Outcome
    Title Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period (Including the Flovent Diskus Treatment Arm)
    Description Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. On mornings for which a treatment visit was scheduled (TV1 through TV9), the PEF was measured and recorded at the investigational site visit. Baseline trough AM PEF was defined as the average of recorded (nonmissing) trough AM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to Flovent Diskus are from an MMRM model that included data for all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
    Time Frame Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set, including participants who contributed at least once to the analysis. Based on blinded data review, data from one site are excluded due to good clinical practice (GCP) concerns.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 101 101 96 101 98 99
    Least Squares Mean (Standard Error) [liters/minute]
    10.85
    (4.245)
    9.39
    (4.193)
    10.29
    (4.362)
    10.40
    (4.254)
    2.52
    (4.453)
    15.97
    (4.283)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3568
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.56
    Confidence Interval (2-Sided) 95%
    -17.42 to 6.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3531
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.68
    Confidence Interval (2-Sided) 95%
    -17.67 to 6.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2724
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -6.58
    Confidence Interval (2-Sided) 95%
    -18.35 to 5.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value =0.3964
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.11
    Confidence Interval (2-Sided) 95%
    -16.95 to 6.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0296
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -13.45
    Confidence Interval (2-Sided) 95%
    -25.57 to -1.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Other Pre-specified Outcome
    Title Change From Baseline In Weekly Average Of Daily Trough (Predose And Pre-Rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period (Including the Flovent Diskus Treatment Arm)
    Description Peak expiratory flow was determined in the AM and in the PM, before administration of study or rescue medications using a handheld electronic peak flow meter. The highest value of triplicate measurements obtained was recorded by the subject's diary device. PM PEF baseline was defined as the average of recorded (nonmissing) PM PEF assessments over the 7 days directly preceding first study drug intake. The p-values for the treatment comparisons to Flovent Diskus are from an MMRM model that included data for all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
    Time Frame Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set, including participants who contributed at least once to the analysis. Based on blinded data review, data from one site are excluded due to good clinical practice (GCP) concerns.
    Arm/Group Title Fp MDPI 50 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Placebo MDPI Flovent Diskus 250mcg
    Arm/Group Description Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    Measure Participants 103 99 96 102 96 99
    Least Squares Mean (Standard Error) [liters/minute]
    4.22
    (4.245)
    6.52
    (4.275)
    7.89
    (4.397)
    11.72
    (4.271)
    3.35
    (4.518)
    12.4
    (4.309)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 400 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9101
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -12.59 to 11.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4634
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -4.51
    Confidence Interval (2-Sided) 95%
    -16.6 to 7.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3333
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.88
    Confidence Interval (2-Sided) 95%
    -17.8 to 6.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1763
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -8.19
    Confidence Interval (2-Sided) 95%
    -20.06 to 3.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Flovent Diskus 250mcg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1469
    Comments 0.05 level of significance.
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Slope
    Estimated Value -9.05
    Confidence Interval (2-Sided) 95%
    -21.3 to 3.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Day 1 to Week 16
    Adverse Event Reporting Description
    Arm/Group Title Flovent Diskus 250 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Fp MDPI 50 mcg Placebo MDPI
    Arm/Group Description Fluticasone propionate (Fp) 250 mcg per dose twice a day (for a total daily dose of 500 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 200 mcg per dose twice a day (for a total daily dose of 400 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 400 mcg per dose twice a day (for a total daily dose of 800 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms. Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
    All Cause Mortality
    Flovent Diskus 250 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Fp MDPI 50 mcg Placebo MDPI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Flovent Diskus 250 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Fp MDPI 50 mcg Placebo MDPI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/106 (0%) 1/107 (0.9%) 1/106 (0.9%) 0/107 (0%) 1/107 (0.9%) 1/106 (0.9%)
    Cardiac disorders
    Myocardial infarction 0/106 (0%) 0 0/107 (0%) 0 1/106 (0.9%) 1 0/107 (0%) 0 0/107 (0%) 0 0/106 (0%) 0
    Infections and infestations
    Kidney infection 0/106 (0%) 0 1/107 (0.9%) 1 0/106 (0%) 0 0/107 (0%) 0 0/107 (0%) 0 0/106 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer 0/106 (0%) 0 0/107 (0%) 0 0/106 (0%) 0 0/107 (0%) 0 1/107 (0.9%) 1 0/106 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/106 (0%) 0 0/107 (0%) 0 0/106 (0%) 0 0/107 (0%) 0 0/107 (0%) 0 1/106 (0.9%) 1
    Other (Not Including Serious) Adverse Events
    Flovent Diskus 250 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Fp MDPI 400 mcg Fp MDPI 50 mcg Placebo MDPI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/106 (3.8%) 4/107 (3.7%) 5/106 (4.7%) 7/107 (6.5%) 5/107 (4.7%) 6/106 (5.7%)
    Nervous system disorders
    Headache 4/106 (3.8%) 4 4/107 (3.7%) 10 5/106 (4.7%) 6 7/107 (6.5%) 9 5/107 (4.7%) 5 6/106 (5.7%) 9

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

    Results Point of Contact

    Name/Title Director, Clinical Research
    Organization Teva Branded Pharmaceutical Products, R&D Inc.
    Phone 215-591-3000
    Email ustevatrials@tevapharm.com
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT01576718
    Other Study ID Numbers:
    • FpS-AS-202
    • 2010-023601-35
    First Posted:
    Apr 12, 2012
    Last Update Posted:
    May 8, 2018
    Last Verified:
    May 1, 2018