A Study of the Effectiveness and Safety of Different Doses of Fluticasone Propionate Taken From a Dry Powder Inhaler in Adolescents and Adults Who Have Asthma That is Not Controlled by Asthma Medications Not Containing Steroids

Asthma Clinical Trial

Official title:

A 12-Week Dose-ranging Study to Evaluate the Efficacy and Safety of Fluticasone Propionate DPI Administered Twice Daily Compared With Placebo in Adolescent and Adult Subjects With Persistent Asthma Uncontrolled on Non-steroidal Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01479621
• Other study ID #: FpS-AS-201
• Secondary ID: 2010-023600-27
• Status: Completed
• Phase: Phase 2
• First received: November 22, 2011
• Last updated: March 19, 2015
• Start date: January 2012
• Est. completion date: August 2013

Study information

• Verified date: March 2015
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug AgencyCroatia: Agency for Medicinal Product and Medical DevicesHungary: National Institute of PharmacyPoland: Ministry of HealthUkraine: State Pharmacological Center - Ministry of HealthUnited States: Food and Drug AdministrationRussia: Pharmacological Committee, Ministry of HealthIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo- and open-label active controlled, parallel-group, multicenter, dose ranging study in male or female subjects ages 12 years and older with persistent asthma who are uncontrolled on non-steroidal therapy. The primary objective of this study is to evaluate the dose response, efficacy and safety of 4 different doses of fluticasone propionate (dose 1, dose 2, dose 3, and dose 4) delivered as Fluticasone Propionate DPI (Dry Powder Inhaler) when administered twice daily.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 622
• Est. completion date: August 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• 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.

6. Reversibility of Disease: Demonstrated a =15% 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 =15%, then the subject is not eligible for the study and will not be allowed to re-screen.

7. Current Asthma Therapy: Subjects must be on a short-acting ß2-agonist alone or a non-corticosteroid maintenance medication (with or without a short-acting ß2-agonist) for = 3 months preceding the Screening Visit. Subjects must not have used an inhaled corticosteroid for at least 6 weeks preceding the Screening Visit.

Exception: Based upon the investigator's judgment that there is no inherent harm in changing the subject's current ICS therapy and the subject provides consent, subjects on low dose ICS (100mcg Fp BID or equivalent) may be switched to a short-acting ß2 agonist alone at a Pre-screening Visit. The subject will be required to return to the clinic to complete the Screening Visit once the 2-week washout period has been completed.

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 its 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 beta 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

1. Non-childbearing potential, defined as:

• Before menarche or > 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

2. 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 > or = 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 is of

3. 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 prior to 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 3 months of the Screening Visit. A subject must not have had any hospitalization for asthma within 6 months 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 non-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 non-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. Clinical visual evidence of oral candidiasis at the Screening Visit.

9. History of any adverse reaction, including immediate or delayed hypersensitivity to any ß2-agonist, sympathomimetic drug, or 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 12 weeks prior to the Screening Visit

• Use of topical corticosteroids (=1% hydrocortisone cream) for dermatological disease is permitted

• Use of intranasal 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 at a stable dose for at least 90 days prior to the Screening Visit and throughout the study for the treatment of allergies is permitted.

14. Use of potent Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, ketoconazole, itraconazole) within 4 weeks prior to the Screening Visit.

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Placebo
Placebo DPI
• Flovent Diskus
Flovent Discus 100mcg BID
• Fluticasone propionate DPI Dose 1
Fluticasone propionate
• Fluticasone propionate DPI Dose 2
Fluticasone propionate
• Fluticasone propionate DPI Dose 3
Fluticasone propionate
• Fluticasone propionate DPI Dose 4
Fluticasone propionate

Locations

Country	Name	City	State
Bulgaria	Teva Investigational Site 59107	Burgas
Bulgaria	Teva Investigational Site 59103	Lovech
Bulgaria	Teva Investigational Site 59106	Pleven
Bulgaria	Teva Investigational Site 59104	Ruse
Bulgaria	Teva Investigational Site 59101	Sofia
Bulgaria	Teva Investigational Site 59102	Sofia
Bulgaria	Teva Investigational Site 59105	Sofia
Croatia	Teva Investigational Site 85105	Split
Croatia	Teva Investigational Site 85102	Zagreb
Croatia	Teva Investigational Site 85103	Zagreb
Croatia	Teva Investigational Site 85104	Zagreb
Hungary	Teva Investigational Site 36107	Balassagyarmat
Hungary	Teva Investigational Site 36104	Budapest
Hungary	Teva Investigational Site 36105	Budapest
Hungary	Teva Investigational Site 36113	Csoma
Hungary	Teva Investigational Site 36103	Miskolc
Hungary	Teva Investigational Site 36108	Mosdos
Hungary	Teva Investigational Site 36102	Nyiregyhaza
Hungary	Teva Investigational Site 36106	Szeged
Hungary	Teva Investigational Site 36109	Szeged
Hungary	Teva Investigational Site 36101	Szombathely
Hungary	Teva Investigational Site 36111	Tatabanya
Israel	Teva Investigational Site 72111	Ashkelon
Israel	Teva Investigational Site 72101	Haifa
Israel	Teva Investigational Site 72102	Jerusalem
Israel	Teva Investigational Site 72104	Jerusalem
Israel	Teva Investigational Site 72109	Kfar Saba
Israel	Teva Investigational Site 72106	Petach Tikva
Israel	Teva Investigational Site 72107	Ramat-Gan
Israel	Teva Investigational Site 72103	Rehovot
Israel	Teva Investigational Site 72110	Tel Aviv
Israel	Teva Investigational Site 72108	Tel-Aviv
Poland	Teva Investigational Site 48107	Bialystok
Poland	Teva Investigational Site 48105	Bydgoszcz
Poland	Teva Investigational Site 48106	Grodzisk Mazowiecki
Poland	Teva Investigational Site 48101	Lodz
Poland	Teva Investigational Site 48108	Poznan
Poland	Teva Investigational Site 48103	Tarnow
Poland	Teva Investigational Site 48104	Wroclaw
Serbia	Teva Investigational Site 81101	Belgrade
Serbia	Teva Investigational Site 81102	Belgrade
Spain	Teva Investigational Site 34101	Badalona
Spain	Teva Investigational Site 34102	Barcelona
Spain	Teva Investigational Site 34103	Salt
Ukraine	Teva Investigational Site 80101	Dnipropetrovsk
Ukraine	Teva Investigational Site 80113	Dnipropetrovsk
Ukraine	Teva Investigational Site 80111	Donetsk
Ukraine	Teva Investigational Site 80103	Kharkiv
Ukraine	Teva Investigational Site 80117	Kharkiv
Ukraine	Teva Investigational Site 80104	Kyiv
Ukraine	Teva Investigational Site 80105	Kyiv
Ukraine	Teva Investigational Site 80106	Kyiv
Ukraine	Teva Investigational Site 80107	Kyiv
Ukraine	Teva Investigational Site 80108	Kyiv
Ukraine	Teva Investigational Site 80109	Kyiv
Ukraine	Teva Investigational Site 80114	Odesa
Ukraine	Teva Investigational Site 80118	Ternopil
Ukraine	Teva Investigational Site 80112	Vinnytsya
Ukraine	Teva Investigational Site 80115	Yalta
Ukraine	Teva Investigational Site 80110	Zaporizhzhia
United States	Teva Investigational Site 11114	Albany	Georgia
United States	Teva Investigational Site 11113	Albuquerque	New Mexico
United States	Teva Investigational Site 11108	Ashland	Oregon
United States	Teva Investigational Site 10173	Bakersfield	California
United States	Teva Investigational Site 10164	Bangor	Maine
United States	Teva Investigational Site 10118	Bellevue	Nebraska
United States	Teva Investigational Site 10158	Bethesda	Maryland
United States	Teva Investigational Site 10119	Boerne	Texas
United States	Teva Investigational Site 10191	Boyton Beach	Florida
United States	Teva Investigational Site 11127	Brandon	Florida
United States	Teva Investigational Site 10114	Brick	New Jersey
United States	Teva Investigational Site 10187	Brooklyn	New York
United States	Teva Investigational Site 10159	Burke	Virginia
United States	Teva Investigational Site 10194	Canton	Ohio
United States	Teva Investigational Site 10145	Centennial	Colorado
United States	Teva Investigational Site 10126	Charleston	South Carolina
United States	Teva Investigational Site 10149	Charleston	South Carolina
United States	Teva Investigational Site 10193	Cherry Hill	New Jersey
United States	Teva Investigational Site 10107	Cincinnati	Ohio
United States	Teva Investigational Site 10123	Cincinnati	Ohio
United States	Teva Investigational Site 11118	Clearwater	Florida
United States	Teva Investigational Site 10172	Colorado Springs	Colorado
United States	Teva Investigational Site 10111	Columbus	Georgia
United States	Teva Investigational Site 10144	Columbus	Ohio
United States	Teva Investigational Site 11124	Columbus	Georgia
United States	Teva Investigational Site 10163	Costa Mesa	California
United States	Teva Investigational Site 10141	Dallas	Texas
United States	Teva Investigational Site 10192	Dallas	Texas
United States	Teva Investigational Site 11135	Dayton	Ohio
United States	Teva Investigational Site 10133	Denver	Colorado
United States	Teva Investigational Site 10154	Denver	Colorado
United States	Teva Investigational Site 11146	Denver	Colorado
United States	Teva Investigational Site 11119	East Providence	Rhode Island
United States	Teva Investigational Site 10148	El Paso	Texas
United States	Teva Investigational Site 10156	Encinitas	California
United States	Teva Investigational Site 10132	Eugene	Oregon
United States	Teva Investigational Site 10102	Fairfax	Virginia
United States	Teva Investigational Site 11101	Fountain Valley	California
United States	Teva Investigational Site 11111	Fresno	California
United States	Teva Investigational Site 10180	Gainesville	Georgia
United States	Teva Investigational Site 11142	Goodyear	Arizona
United States	Teva Investigational Site 10151	Granada Hills	California
United States	Teva Investigational Site 10170	Greenfield	Wisconsin
United States	Teva Investigational Site 11136	Henderson	Nevada
United States	Teva Investigational Site 11141	Hialeah	Florida
United States	Teva Investigational Site 10105	High Point	North Carolina
United States	Teva Investigational Site 10101	Hillsborough	New Jersey
United States	Teva Investigational Site 10165	Homewood	Alabama
United States	Teva Investigational Site 10157	Huntington Beach	California
United States	Teva Investigational Site 10176	Huntington Beach	California
United States	Teva Investigational Site 11109	Idaho Falls	Idaho
United States	Teva Investigational Site 10184	Iowa City	Iowa
United States	Teva Investigational Site 11140	Kissimee	Florida
United States	Teva Investigational Site 10110	Largo	Maryland
United States	Teva Investigational Site 10168	Lawrenceville	Georgia
United States	Teva Investigational Site 11143	Layton	Utah
United States	Teva Investigational Site 10181	Lincoln	Rhode Island
United States	Teva Investigational Site 11149	Little Rock	Arkansas
United States	Teva Investigational Site 10147	Long Beach	California
United States	Teva Investigational Site 11105	Manassas	Virginia
United States	Teva Investigational Site 10135	Medford	Oregon
United States	Teva Investigational Site 10116	Meridian	Idaho
United States	Teva Investigational Site 10113	Metairie	Louisiana
United States	Teva Investigational Site 10137	Miami	Florida
United States	Teva Investigational Site 10153	Miami	Florida
United States	Teva Investigational Site 11120	Miami	Florida
United States	Teva Investigational Site 11128	Miami	Florida
United States	Teva Investigational Site 11132	Miami	Florida
United States	Teva Investigational Site 11145	Miami	Florida
United States	Teva Investigational Site 11115	Middleburg Heights	Ohio
United States	Teva Investigational Site 10131	Minneapolis	Minnesota
United States	Teva Investigational Site 11110	Napa	California
United States	Teva Investigational Site 10120	New York	New York
United States	Teva Investigational Site 10190	Newburgh	New York
United States	Teva Investigational Site 10136	Newport Beach	California
United States	Teva Investigational Site 11104	Normal	Pennsylvania
United States	Teva Investigational Site 10138	North Dartmouth	Massachusetts
United States	Teva Investigational Site 10146	North Dartmouth	Massachusetts
United States	Teva Investigational Site 11122	North Hollywood	California
United States	Teva Investigational Site 10167	North Syracuse	New York
United States	Teva Investigational Site 10171	Ocala	Florida
United States	Teva Investigational Site 10160	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10174	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10198	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10150	Omaha	Nebraska
United States	Teva Investigational Site 11144	Omaha	Nebraska
United States	Teva Investigational Site 10140	Orange	California
United States	Teva Investigational Site 10199	Orangeburg	South Carolina
United States	Teva Investigational Site 10197	Palmdale	California
United States	Teva Investigational Site 10183	Philadelphia	Pennsylvania
United States	Teva Investigational Site 10166	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 10142	Portland	Oregon
United States	Teva Investigational Site 10162	Providence	Rhode Island
United States	Teva Investigational Site 10195	Provo	Utah
United States	Teva Investigational Site 10122	Raleigh	North Carolina
United States	Teva Investigational Site 10185	Redwood City	California
United States	Teva Investigational Site 10108	Richmond	Virginia
United States	Teva Investigational Site 10143	Riverside	California
United States	Teva Investigational Site 10112	Rochester	New York
United States	Teva Investigational Site 11137	Roseville	California
United States	Teva Investigational Site 10115	San Antonio	Texas
United States	Teva Investigational Site 11133	San Antonio	Texas
United States	Teva Investigational Site 11134	San Antonio	Texas
United States	Teva Investigational Site 10130	San Diego	California
United States	Teva Investigational Site 10182	San Diego	California
United States	Teva Investigational Site 10179	San Jose	California
United States	Teva Investigational Site 10178	Sarasota	Florida
United States	Teva Investigational Site 10104	Scottsdale	Arizona
United States	Teva Investigational Site 10155	Skillman	New Jersey
United States	Teva Investigational Site 10127	South Bend	Indiana
United States	Teva Investigational Site 10134	South Burlington	Vermont
United States	Teva Investigational Site 11103	South Miami	Florida
United States	Teva Investigational Site 11131	Spartanburg	South Carolina
United States	Teva Investigational Site 10124	Spokane	Washington
United States	Teva Investigational Site 10189	St Louis	Missouri
United States	Teva Investigational Site 11147	St Louis	Missouri
United States	Teva Investigational Site 10175	St. Louis	Missouri
United States	Teva Investigational Site 10106	Stockton	California
United States	Teva Investigational Site 11117	Tacoma	Washington
United States	Teva Investigational Site 11125	Tacoma	Washington
United States	Teva Investigational Site 10161	Tallahassee	Florida
United States	Teva Investigational Site 10139	Tampa	Florida
United States	Teva Investigational Site 10121	Upland	Pennsylvania
United States	Teva Investigational Site 10103	Waco	Texas
United States	Teva Investigational Site 10129	Walnut Creek	California
United States	Teva Investigational Site 10196	Waterbury	Connecticut
United States	Teva Investigational Site 10188	West Orange	New Jersey
United States	Teva Investigational Site 10128	Wheat Ridge	Colorado
United States	Teva Investigational Site 10177	Wheaton	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries	PPD

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Hungary,  Israel,  Poland,  Serbia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in trough of Forced Expiratory Volume in the first second (FEV1) over the Treatment Period		Baseline, 12 weeks	No
Secondary	Change from baseline in weekly average of daily trough (pre-dose and pre-rescue bronchodilator) AM PEF over the Treatment Period		Baseline, 12 weeks	No
Secondary	Change from baseline in weekly average of daily PM PEF over the Treatment Period		Baseline, 12 weeks	No
Secondary	Change from baseline in the percentage of symptom-free 24-hour periods during the Treatment Period		Baseline, 12 weeks	No
Secondary	Change from baseline in the percentage of rescue-free 24-hour periods during the Treatment Period		Baseline, 12 weeks	No