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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01576718
• Other study ID #: FpS-AS-202
• Secondary ID: 2010-023601-35
• Status: Completed
• Phase: Phase 2
• Start date: April 2012
• Est. completion date: October 2013

Study information

• Verified date: May 2018
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 889
• Est. completion date: October 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 ß2 agonist and inhaled corticosteroid for a minimum of 8 weeks before the Screening Visit and have been maintained on a stable dose of inhaled corticosteroids 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 ß2-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 ß2-Agonists: All subjects must be able to replace their current short-acting ß2-agonists with albuterol/salbutamol inhalation aerosol at the Screening Visit for use as needed for the duration of the study. The use of spacer devices with the metered dose inhaler (MDI) will not be allowed during the study with exception of it's use during reversibility testing at the Screening Visit. Nebulized albuterol/salbutamol will not be allowed at any time during the study. Subjects must be able to withhold all inhaled short-acting ß2 sympathomimetic bronchodilators for at least 6 hours prior to all study visits.

9. If female, is currently not pregnant, breast feeding, or attempting to become pregnant, has a negative serum pregnancy test, and is of

• Non-childbearing potential, defined as:

• Before menarche, or

• 1 year post-menopausal, or

• Surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy), or

• Congenital sterility, or

• Diagnosed as infertile 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.

Related Conditions & MeSH terms

• Asthma

Intervention

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:
• 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:
• 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.
• albuterol/salbutamol
A short-acting ß2-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).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products, R&D Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Croatia,  Germany,  Greece,  Hungary,  Ireland,  Israel,  New Zealand,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	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.	Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Other	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)	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.	Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Other	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)	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.	Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Primary	Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period	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.	Baseline (Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Secondary	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	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.	Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Secondary	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	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.	Baseline (Days -6 to Day 1 pre-dose), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Secondary	The Kaplan-Meier Estimate Of The Probability Of Remaining In The Study At 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.	Day 1 to Week 12
Secondary	Change From Baseline In The Percentage Of Rescue-Free 24-Hour Periods	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.	Baseline (Day -6 to Day 1 predose), Treatment (Day 1 to Week 12)
Secondary	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
Secondary	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
Secondary	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
Secondary	Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period	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.	Day 1 to Week 12
Secondary	Patients With Positive Swab Test Results for Oral Candidiasis	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.	Screening (Days -21 to -14), Randomization (Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12
Secondary	24-Hour Urinary Cortisol Excretion at Baseline, Week 12 and 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.	Baseline (Day 1), Week 12, Endpoint