Clinical trial NCT01576718: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Dose ranging
Fluticasone Propionate
Dry Powder Inhaler (DPI)
High Dose ICS
Asthma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-12
Enrollment: 889
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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
6. 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.
7. 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.
8. 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.
9. If female, is currently not pregnant, breast feeding, or attempting to become pregnant, has a negative serum pregnancy test, and is of

   * Non-childbearing potential, defined as:

     * Before menarche, or
     * 1 year post-menopausal, or
     * Surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy), or
     * Congenital sterility, or
     * Diagnosed as infertile 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
10. 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.
4. Presence of glaucoma, cataracts, ocular herpes simplex, or malignancy other than basal cell carcinoma.
5. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular (e.g., congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia or coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine (e.g., uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison's disease, Cushing's syndrome), gastrointestinal (e.g., poorly-controlled peptic ulcer, GERD), or pulmonary (e.g., chronic bronchitis, emphysema, bronchiectasis with the need for treatment, cystic fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease). 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.
6. Have any of the following conditions that, in the judgment of the investigator, might cause participation in this study to be detrimental to the subject, including, but not limited to:

   * Current malignancy excluding basal cell carcinoma; History of malignancy is acceptable only if the subject has been in remission for 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
7. History of a positive test for HIV, hepatitis B or hepatitis C infection.
8. Untreated oral candidiasis at the Screening Visit. Subjects with clinical visual evidence of oral candidiasis and who agree to receive treatment and comply with appropriate medical monitoring may enter the study
9. History of any adverse reaction to any intranasal, inhaled or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the dry powder inhalers (Spiromax or Diskus) used in the study (i.e., lactose).
10. History of severe allergy to milk protein.
11. Use of systemic, oral or depot corticosteroids within 4 weeks prior to the Screening Visit

    * Use of topical corticosteroids (≤1% hydrocortisone cream) for dermatological disease is permitted
    * Use of intranasal corticosteroids or ocular corticosteroids at a stable dose for at least 4 weeks prior to the Screening Visit and throughout the study is permitted
12. Use of immunosuppressive medications within 4 weeks prior to the Screening Visit and during the study.
13. Immunotherapy for the treatment of allergy at a stable maintenance dose for at least 90 days prior to the Screening Visit and which will remain at a stable dose without escalation throughout the study is permitted.
14. 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.
15. History of alcohol or drug abuse within two years preceding the Screening Visit.
16. 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).
17. Study participation by clinical investigator site employees and/or their immediate relatives.
18. 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.
19. 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.
20. 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.

Primary outcomes:
measure: Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period
timeFrame: Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Secondary outcomes:
measure: 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
timeFrame: Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
measure: 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
timeFrame: Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
measure: The Kaplan-Meier Estimate Of The Probability Of Remaining In The Study At Week 12
timeFrame: Day 1 to Week 12
measure: Change From Baseline In The Percentage Of Rescue-Free 24-Hour Periods
timeFrame: Baseline (Day -6 to Day 1 predose), Treatment (Day 1 to Week 12)
measure: Area Under The Plasma Concentration-Time Curve From Time Zero To The Time Of The Last Measurable Concentration (AUC0-t)
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Time Of Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
timeFrame: Day 1 to Week 12
measure: Patients With Positive Swab Test Results for Oral Candidiasis
timeFrame: Screening (Days -21 to -14), Randomization (Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12
measure: 24-Hour Urinary Cortisol Excretion at Baseline, Week 12 and Endpoint
timeFrame: Baseline (Day 1), Week 12, Endpoint
Other outcomes:
measure: 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)
timeFrame: Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
measure: 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)
timeFrame: Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
measure: 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)
timeFrame: Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 10504
state: Alabama
city: Homewood
country: United States
facility: Teva Investigational Site 10565
state: Alabama
city: Goodyear
country: United States
facility: Teva Investigational Site 11527
state: Arizona
city: Tucson
country: United States
facility: Teva Investigational Site 10516
state: Arizona
city: Bakersfield
country: United States
facility: Teva Investigational Site 10573
state: California
city: Costa Mesa
country: United States
facility: Teva Investigational Site 11518
state: California
city: Fountain Valley
country: United States
facility: Teva Investigational Site 10590
state: California
city: Granada Hills
country: United States
facility: Teva Investigational Site 10551
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 11520
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 11545
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 10547
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 11549
state: California
city: Mission Viejo
country: United States
facility: Teva Investigational Site 10503
state: California
city: Newport Beach
country: United States
facility: Teva Investigational Site 10536
state: California
city: Orange
country: United States
facility: Teva Investigational Site 10540
state: California
city: Orange
country: United States
facility: Teva Investigational Site 11551
state: California
city: Palmdale
country: United States
facility: Teva Investigational Site 10578
state: California
city: Redwood City
country: United States
facility: Teva Investigational Site 10585
state: California
city: Rolling Hills Estates
country: United States
facility: Teva Investigational Site 11538
state: California
city: Roseville
country: United States
facility: Teva Investigational Site 11522
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 10582
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 11554
state: California
city: San Jose
country: United States
facility: Teva Investigational Site 10563
state: California
city: Santa Monica
country: United States
facility: Teva Investigational Site 11556
state: California
city: Stockton
country: United States
facility: Teva Investigational Site 10506
state: California
city: Walnut Creek
country: United States
facility: Teva Investigational Site 10529
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 10545
state: Colorado
city: Colorado Springs
country: United States
facility: Teva Investigational Site 10572
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 10533
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 11531
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 11542
state: Colorado
city: Wheat Ridge
country: United States
facility: Teva Investigational Site 11569
state: Colorado
city: Waterbury
country: United States
facility: Teva Investigational Site 10528
state: Connecticut
city: Boynton Beach
country: United States
facility: Teva Investigational Site 10556
state: Florida
city: Brandon
country: United States
facility: Teva Investigational Site 11513
state: Florida
city: Clearwater
country: United States
facility: Teva Investigational Site 11507
state: Florida
city: Fort Myers
country: United States
facility: Teva Investigational Site 11546
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 11526
state: Florida
city: Kissimmee
country: United States
facility: Teva Investigational Site 11525
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 10537
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 10553
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 11508
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 11514
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 11516
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 11530
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 11570
state: Florida
city: Ocala
country: United States
facility: Teva Investigational Site 10571
state: Florida
city: Sarasota
country: United States
facility: Teva Investigational Site 11537
state: Florida
city: South Miami
country: United States
facility: Teva Investigational Site 10593
state: Florida
city: Tallahassee
country: United States
facility: Teva Investigational Site 11555
state: Florida
city: Tamarac
country: United States
facility: Teva Investigational Site 10554
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 10539
state: Florida
city: Valrico
country: United States
facility: Teva Investigational Site 10525
state: Florida
city: Albany
country: United States
facility: Teva Investigational Site 11504
state: Georgia
city: Columbus
country: United States
facility: Teva Investigational Site 10511
state: Georgia
city: Columbus
country: United States
facility: Teva Investigational Site 11510
state: Georgia
city: Columbus
country: United States
facility: Teva Investigational Site 11572
state: Georgia
city: Lawrenceville
country: United States
facility: Teva Investigational Site 10568
state: Georgia
city: Lilburn
country: United States
facility: Teva Investigational Site 10586
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 11539
state: Georgia
city: Stockbridge
country: United States
facility: Teva Investigational Site 10543
state: Georgia
city: Indianapolis
country: United States
facility: Teva Investigational Site 11558
state: Indiana
city: South Bend
country: United States
facility: Teva Investigational Site 10527
state: Indiana
city: Iowa City
country: United States
facility: Teva Investigational Site 10584
state: Iowa
city: Overland Park
country: United States
facility: Teva Investigational Site 11501
state: Kansas
city: Lexington
country: United States
facility: Teva Investigational Site 10591
state: Kentucky
city: Louisville
country: United States
facility: Teva Investigational Site 11567
state: Kentucky
city: Metairie
country: United States
facility: Teva Investigational Site 10513
state: Louisiana
city: Bangor
country: United States
facility: Teva Investigational Site 10564
state: Maine
city: Baltimore
country: United States
facility: Teva Investigational Site 11548
state: Maryland
city: Largo
country: United States
facility: Teva Investigational Site 10510
state: Maryland
city: Wheaton
country: United States
facility: Teva Investigational Site 10577
state: Maryland
city: Brockton
country: United States
facility: Teva Investigational Site 10538
state: Massachusetts
city: North Dartmouth
country: United States
facility: Teva Investigational Site 10546
state: Massachusetts
city: Troy
country: United States
facility: Teva Investigational Site 11502
state: Michigan
city: Plymouth
country: United States
facility: Teva Investigational Site 10531
state: Minnesota
city: Columbia
country: United States
facility: Teva Investigational Site 11562
state: Missouri
city: Columbia
country: United States
facility: Teva Investigational Site 11563
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 10552
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 10575
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 10589
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 11532
state: Missouri
city: Bellevue
country: United States
facility: Teva Investigational Site 10518
state: Nebraska
city: Omaha
country: United States
facility: Teva Investigational Site 10550
state: Nebraska
city: Omaha
country: United States
facility: Teva Investigational Site 11529
state: Nebraska
city: Las Vegas
country: United States
facility: Teva Investigational Site 11571
state: Nevada
city: Cherry Hill
country: United States
facility: Teva Investigational Site 10559
state: New Jersey
city: Edison
country: United States
facility: Teva Investigational Site 11566
state: New Jersey
city: Hillsborough
country: United States
facility: Teva Investigational Site 10501
state: New Jersey
city: Ocean City
country: United States
facility: Teva Investigational Site 11550
state: New Jersey
city: West Orange
country: United States
facility: Teva Investigational Site 10588
state: New Jersey
city: Albuquerque
country: United States
facility: Teva Investigational Site 11503
state: New Mexico
city: Bronx
country: United States
facility: Teva Investigational Site 10580
state: New York
city: Brooklyn
country: United States
facility: Teva Investigational Site 10587
state: New York
city: New York
country: United States
facility: Teva Investigational Site 10520
state: New York
city: Newburgh
country: United States
facility: Teva Investigational Site 10532
state: New York
city: North Syracuse
country: United States
facility: Teva Investigational Site 10567
state: New York
city: Rochester
country: United States
facility: Teva Investigational Site 10512
state: New York
city: Canton
country: United States
facility: Teva Investigational Site 10522
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 10507
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 10523
state: Ohio
city: Columbus
country: United States
facility: Teva Investigational Site 10544
state: Ohio
city: Dayton
country: United States
facility: Teva Investigational Site 11521
state: Ohio
city: Middleburg Heights
country: United States
facility: Teva Investigational Site 11505
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 10560
state: Oklahoma
city: Oklahoma City
country: United States
facility: Teva Investigational Site 10574
state: Oklahoma
city: Oklahoma City
country: United States
facility: Teva Investigational Site 10579
state: Oklahoma
city: Tulsa
country: United States
facility: Teva Investigational Site 11544
state: Oklahoma
city: Ashland
country: United States
facility: Teva Investigational Site 10598
state: Oregon
city: Medford
country: United States
facility: Teva Investigational Site 11543
state: Oregon
city: Portland
country: United States
facility: Teva Investigational Site 11557
state: Oregon
city: Altoona
country: United States
facility: Teva Investigational Site 10509
state: Pennsylvania
city: Philadelphia
country: United States
facility: Teva Investigational Site 10555
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Teva Investigational Site 10566
state: Pennsylvania
city: Upland
country: United States
facility: Teva Investigational Site 10521
state: Pennsylvania
city: Lincoln
country: United States
facility: Teva Investigational Site 10581
state: Rhode Island
city: Providence
country: United States
facility: Teva Investigational Site 10562
state: Rhode Island
city: Charleston
country: United States
facility: Teva Investigational Site 10526
state: South Carolina
city: Charleston
country: United States
facility: Teva Investigational Site 11547
state: South Carolina
city: Orangeburg
country: United States
facility: Teva Investigational Site 10583
state: South Carolina
city: Spartanburg
country: United States
facility: Teva Investigational Site 10517
state: South Carolina
city: Spartanburg
country: United States
facility: Teva Investigational Site 11515
state: South Carolina
city: Boerne
country: United States
facility: Teva Investigational Site 10519
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 10541
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 10542
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 10548
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 11552
state: Texas
city: Fort Worth
country: United States
facility: Teva Investigational Site 11512
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 11565
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 11568
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 10515
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 10569
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 11517
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 11519
state: Texas
city: Waco
country: United States
facility: Teva Investigational Site 11560
state: Texas
city: Layton
country: United States
facility: Teva Investigational Site 11528
state: Utah
city: Provo
country: United States
facility: Teva Investigational Site 10576
state: Utah
city: South Burlington
country: United States
facility: Teva Investigational Site 10534
state: Vermont
city: Fairfax
country: United States
facility: Teva Investigational Site 10502
state: Virginia
city: Manassas
country: United States
facility: Teva Investigational Site 10595
state: Virginia
city: Richmond
country: United States
facility: Teva Investigational Site 10508
state: Virginia
city: Bellingham
country: United States
facility: Teva Investigational Site 11561
state: Washington
city: Seattle
country: United States
facility: Teva Investigational Site 11541
state: Washington
city: Spokane
country: United States
facility: Teva Investigational Site 10524
state: Washington
city: Tacoma
country: United States
facility: Teva Investigational Site 10530
state: Washington
city: Tacoma
country: United States
facility: Teva Investigational Site 11511
state: Washington
city: Greenfield
country: United States
facility: Teva Investigational Site 10570
state: Wisconsin
city: Greenfield
country: United States
facility: Teva Investigational Site 11559
state: Wisconsin
city: Bedford Park
country: Australia
facility: Teva Investigational Site 85570
city: Parkville
country: Australia
facility: Teva Investigational Site 85571
city: Burgas
country: Bulgaria
facility: Teva Investigational Site 59507
city: Lovech
country: Bulgaria
facility: Teva Investigational Site 59503
city: Pleven
country: Bulgaria
facility: Teva Investigational Site 59506
city: Ruse
country: Bulgaria
facility: Teva Investigational Site 59504
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59501
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59502
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59505
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59508
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59509
city: Burlington
country: Canada
facility: Teva Investigational Site 11594
state: Ontario
city: Etobicoke
country: Canada
facility: Teva Investigational Site 11595
state: Ontario
city: Sarnia
country: Canada
facility: Teva Investigational Site 11592
state: Ontario
city: Toronto
country: Canada
facility: Teva Investigational Site 11590
state: Ontario
city: Newmarket
country: Canada
facility: Teva Investigational Site 11591
city: Zagreb
country: Croatia
facility: Teva Investigational Site 85501
city: Zagreb
country: Croatia
facility: Teva Investigational Site 85502
city: Zagreb
country: Croatia
facility: Teva Investigational Site 85503
city: Zagreb
country: Croatia
facility: Teva Investigational Site 85504
city: Berlin
country: Germany
facility: Teva Investigational Site 70561
city: Bonn
country: Germany
facility: Teva Investigational Site 70564
city: Cottbus
country: Germany
facility: Teva Investigational Site 70557
city: Delitzsch
country: Germany
facility: Teva Investigational Site 70553
city: Frankfurt
country: Germany
facility: Teva Investigational Site 70558
city: Hamburg
country: Germany
facility: Teva Investigational Site 70562
city: Hanover
country: Germany
facility: Teva Investigational Site 70560
city: Leipzig
country: Germany
facility: Teva Investigational Site 70555
city: Magdeburg
country: Germany
facility: Teva Investigational Site 70556
city: Munchen
country: Germany
facility: Teva Investigational Site 70550
city: Munchen
country: Germany
facility: Teva Investigational Site 70554
city: Munster
country: Germany
facility: Teva Investigational Site 70552
city: Nurnberg
country: Germany
facility: Teva Investigational Site 70563
city: Rudersdorf
country: Germany
facility: Teva Investigational Site 70551
city: Wiesbaden
country: Germany
facility: Teva Investigational Site 70559
city: Athens
country: Greece
facility: Teva Investigational Site 85533
city: Athens
country: Greece
facility: Teva Investigational Site 85534
city: Heraklion
country: Greece
facility: Teva Investigational Site 85531
city: Larissa
country: Greece
facility: Teva Investigational Site 85532
city: Thessaloniki
country: Greece
facility: Teva Investigational Site 85530
city: Balassagyarmat
country: Hungary
facility: Teva Investigational Site 36507
city: Budapest
country: Hungary
facility: Teva Investigational Site 36504
city: Budapest
country: Hungary
facility: Teva Investigational Site 36505
city: Csoma
country: Hungary
facility: Teva Investigational Site 36514
city: Erd
country: Hungary
facility: Teva Investigational Site 36516
city: Kaba
country: Hungary
facility: Teva Investigational Site 36513
city: Kaposvar
country: Hungary
facility: Teva Investigational Site 36515
city: Miskolc
country: Hungary
facility: Teva Investigational Site 36503
city: Nyiregyhaza
country: Hungary
facility: Teva Investigational Site 36502
city: Siofok
country: Hungary
facility: Teva Investigational Site 36510
city: Szarvas
country: Hungary
facility: Teva Investigational Site 36517
city: Szazhalombatta
country: Hungary
facility: Teva Investigational Site 36508
city: Szeged
country: Hungary
facility: Teva Investigational Site 36506
city: Szeged
country: Hungary
facility: Teva Investigational Site 36509
city: Szombathely
country: Hungary
facility: Teva Investigational Site 36501
city: Veszprem
country: Hungary
facility: Teva Investigational Site 36512
city: Dublin
country: Ireland
facility: Teva Investigational Site 59550
city: Dublin
country: Ireland
facility: Teva Investigational Site 59551
city: Ashkelon
country: Israel
facility: Teva Investigational Site 72511
city: Haifa
country: Israel
facility: Teva Investigational Site 72501
city: Haifa
country: Israel
facility: Teva Investigational Site 72512
city: Jerusalem
country: Israel
facility: Teva Investigational Site 72502
city: Jerusalem
country: Israel
facility: Teva Investigational Site 72504
city: Kfar Saba
country: Israel
facility: Teva Investigational Site 72509
city: Petach Tikva
country: Israel
facility: Teva Investigational Site 72506
city: Ramat-Gan
country: Israel
facility: Teva Investigational Site 72507
city: Rehovot
country: Israel
facility: Teva Investigational Site 72503
city: Tel Aviv
country: Israel
facility: Teva Investigational Site 72510
city: Tel-Aviv
country: Israel
facility: Teva Investigational Site 72508
city: Zerifin
country: Israel
facility: Teva Investigational Site 72505
city: Auckland
country: New Zealand
facility: Teva Investigational Site 81571
city: Christchurch
country: New Zealand
facility: Teva Investigational Site 81572
city: Tauranga
country: New Zealand
facility: Teva Investigational Site 81573
city: Wellington
country: New Zealand
facility: Teva Investigational Site 81570
city: Bialystok
country: Poland
facility: Teva Investigational Site 48507
city: Bydgoszcz
country: Poland
facility: Teva Investigational Site 48505
city: Grodzisk Mazowiecki
country: Poland
facility: Teva Investigational Site 48506
city: Lodz
country: Poland
facility: Teva Investigational Site 48501
city: Lodz
country: Poland
facility: Teva Investigational Site 48509
city: Lublin
country: Poland
facility: Teva Investigational Site 48513
city: Poznan
country: Poland
facility: Teva Investigational Site 48508
city: Poznan
country: Poland
facility: Teva Investigational Site 48512
city: Strzelce Opolskie
country: Poland
facility: Teva Investigational Site 48502
city: Tarnow
country: Poland
facility: Teva Investigational Site 48503
city: Wroclaw
country: Poland
facility: Teva Investigational Site 48504
city: Brasov
country: Romania
facility: Teva Investigational Site 81534
city: Brasov
country: Romania
facility: Teva Investigational Site 81539
city: Bucharest
country: Romania
facility: Teva Investigational Site 81533
city: Bucharest
country: Romania
facility: Teva Investigational Site 81535
city: Bucharest
country: Romania
facility: Teva Investigational Site 81537
city: Cluj-Napoca
country: Romania
facility: Teva Investigational Site 81531
city: Cluj-Napoca
country: Romania
facility: Teva Investigational Site 81536
city: Targu Mures
country: Romania
facility: Teva Investigational Site 81530
city: Timisoara
country: Romania
facility: Teva Investigational Site 81532
city: Timisoara
country: Romania
facility: Teva Investigational Site 81538
city: Barnaul
country: Russian Federation
facility: Teva Investigational Site 70505
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 70502
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 70511
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 70512
city: Ryazan
country: Russian Federation
facility: Teva Investigational Site 70508
city: Samara
country: Russian Federation
facility: Teva Investigational Site 70509
city: Smolensk
country: Russian Federation
facility: Teva Investigational Site 70507
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 70501
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 70504
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 70510
city: Tomsk
country: Russian Federation
facility: Teva Investigational Site 70506
city: Yaroslavl
country: Russian Federation
facility: Teva Investigational Site 70503
city: Belgrade
country: Serbia
facility: Teva Investigational Site 81501
city: Bloemfontein
country: South Africa
facility: Teva Investigational Site 36551
city: Cape Town
country: South Africa
facility: Teva Investigational Site 36552
city: Cape Town
country: South Africa
facility: Teva Investigational Site 36555
city: Port Elizabeth
country: South Africa
facility: Teva Investigational Site 36550
city: Thabazimbi
country: South Africa
facility: Teva Investigational Site 36553
city: Witbank
country: South Africa
facility: Teva Investigational Site 36554
city: Aranjuez
country: Spain
facility: Teva Investigational Site 34507
city: Badalona
country: Spain
facility: Teva Investigational Site 34501
city: Barcelona
country: Spain
facility: Teva Investigational Site 34502
city: Barcelona
country: Spain
facility: Teva Investigational Site 34510
city: Bilbao
country: Spain
facility: Teva Investigational Site 34509
city: Lleida
country: Spain
facility: Teva Investigational Site 34506
city: Madrid
country: Spain
facility: Teva Investigational Site 34505
city: Salt
country: Spain
facility: Teva Investigational Site 34503
city: Santiago de Compostela
country: Spain
facility: Teva Investigational Site 34504
city: Valencia
country: Spain
facility: Teva Investigational Site 34508
city: Vitoria
country: Spain
facility: Teva Investigational Site 34511
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 80501
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 80513
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 80511
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 80502
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 80503
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80504
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80505
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80506
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80507
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80508
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80509
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80517
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80519
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80520
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 80521
city: Odesa
country: Ukraine
facility: Teva Investigational Site 80514
city: Simferopol
country: Ukraine
facility: Teva Investigational Site 80516
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 80512
city: Yalta
country: Ukraine
facility: Teva Investigational Site 80515
city: Zaporizhia
country: Ukraine
facility: Teva Investigational Site 80522
city: Zaporizhzhia
country: Ukraine
facility: Teva Investigational Site 80510
city: Zaporizhzhya
country: Ukraine
facility: Teva Investigational Site 80518
city: Cottingham
country: United Kingdom
facility: Teva Investigational Site 34582
city: London
country: United Kingdom
facility: Teva Investigational Site 34584
city: Penzance
country: United Kingdom
facility: Teva Investigational Site 34585
city: Torpoint
country: United Kingdom
facility: Teva Investigational Site 34580
city: Watford
country: United Kingdom
facility: Teva Investigational Site 34581
Study officials:
References:
citation: Bernstein DI, Gillespie M, Song S, Steinfeld J. Safety, efficacy, and dose response of fluticasone propionate delivered via the novel MDPI in patients with severe asthma: A randomized, controlled, dose-ranging study. J Asthma. 2017 Aug;54(6):559-569. doi: 10.1080/02770903.2016.1242137. Epub 2016 Oct 24.