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

May 2, 2017 updated by: Teva Branded Pharmaceutical Products R&D, Inc.

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

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 delivered as Fluticasone Propionate DPI (Dry Powder Inhaler) when administered twice daily.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

909

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 β2-agonist alone or a non-corticosteroid maintenance medication (with or without a short-acting β2-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 β2 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 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 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 β2-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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fp MDPI 12.5 mcg

Fluticasone propionate (Fp) 12.5 mcg per dose twice a day (for a total daily dose of 25 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner.

During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
Drug: albuterol/salbutamol
A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Other Names:
  • short-acting β2-adrenergic agonists
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 12.5, 25, 50 or 100 mcg of Fp one inhalation twice a day for a total daily dose of 25, 50, 100 or 200 mcg. Study drug was administered in the morning and in the evening

Other Names:
  • Fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder
Experimental: Fp MDPI 25 mcg

Fluticasone propionate (Fp) 25 mcg per dose twice a day (for a total daily dose of 50 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner.

During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
Drug: albuterol/salbutamol
A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Other Names:
  • short-acting β2-adrenergic agonists
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 12.5, 25, 50 or 100 mcg of Fp one inhalation twice a day for a total daily dose of 25, 50, 100 or 200 mcg. Study drug was administered in the morning and in the evening

Other Names:
  • Fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder
Experimental: Fp MDPI 50 mcg

Fluticasone propionate (Fp) 50 mcg per dose twice a day (for a total daily dose of 100 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner.

During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
Drug: albuterol/salbutamol
A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Other Names:
  • short-acting β2-adrenergic agonists
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 12.5, 25, 50 or 100 mcg of Fp one inhalation twice a day for a total daily dose of 25, 50, 100 or 200 mcg. Study drug was administered in the morning and in the evening

Other Names:
  • Fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder
Experimental: Fp MDPI 100 mcg

Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner.

During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
Drug: albuterol/salbutamol
A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Other Names:
  • short-acting β2-adrenergic agonists
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 12.5, 25, 50 or 100 mcg of Fp one inhalation twice a day for a total daily dose of 25, 50, 100 or 200 mcg. Study drug was administered in the morning and in the evening

Other Names:
  • Fluticasone propionate
  • Fp SPIROMAX® Inhalation Powder
Experimental: Placebo MDPI
Placebo twice a day using a multidose dry powder inhaler (MDPI) for 12 weeks in a double-blind manner. During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
Drug: albuterol/salbutamol
A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Other Names:
  • short-acting β2-adrenergic agonists
Drug: Placebo MDPI
Placebo multidose dry powder inhaler in the morning and evening. Placebo MDPI was provided in devices identical in appearance to Fp MDPI.
Experimental: Flovent Diskus 100mcg

Fluticasone propionate (Fp) 100 mcg per dose twice a day (for a total daily dose of 200 mcg) using a multidose dry powder inhaler (MDPI) for 12 weeks in an open-label manner.

During the run-in and the treatment periods, all subjects replaced their current rescue medication with albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) (90 mcg/actuation) for use on an as needed basis for the relief of asthma symptoms.
Drug: albuterol/salbutamol
A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Other Names:
  • short-acting β2-adrenergic agonists
Drug: Flovent Diskus
Flovent Diskus contains the active ingredient fluticasone propionate (Fp). Flovent Diskus 100 mcg was used twice a day, once in the morning and evening, for a total daily dose of 200 mcg of Fp. This therapy was not blinded as the inhaler device was different than the MDPI used in the other treatment arms.
Other Names:
  • Fluticasone propionate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period
Time Frame: Baseline (Day 1, pre-dose), During Study (Days 7, 14, 28, 56 and 84 pre-dose)

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), During Study (Days 7, 14, 28, 56 and 84 pre-dose)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Baseline (Days -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)

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 -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)
Change From Baseline In Weekly Average Of Daily Evening Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period
Time Frame: Baseline (Days -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)

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 -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)
Change From Baseline in the Percentage of Rescue-Free 24-hour Periods During the 12-Week Treatment Period
Time Frame: Baseline (Days -7 to -1), During Study (Days 1-84)

The number of inhalations of rescue medication used each day and each night was recorded in the subject's diary device.

Change from baseline in the percentage of rescue-free 24-hour periods was analyzed with a marginal (also called population averaged) logistic model. The model included 2 time points of measurement for each subject: the baseline and the treatment period. The model contained covariates for sex, age, and treatment. The model for the 2 time points was considered as an incomplete randomized block model, with each subject as a block, receiving the baseline level in 1 sub-block and either active treatment or placebo in the other sub-block. The generalized estimating equation (GEE) algorithm was used to fit the model, using a robust estimator for the variance which provided a proper adjustment for possible correlation between the 2 measurements on each subject.

Measure type are estimated mean and measure of dispersion is the standard error of the estimated mean.
Baseline (Days -7 to -1), During Study (Days 1-84)
Kaplan-Meier Estimate of Probability of Remaining in the Study at Week 12
Time Frame: Day 1 to Day 84
The time to withdrawal due to stopping criteria was compared between the treatment groups with the log rank test. The Kaplan-Meier estimate of the probability of remaining in the study at week 12 with 95% CI was presented by treatment group. Subjects who completed the study were censored at the date of completion, subjects who withdrew for reasons other than stopping criteria were censored at the time of withdrawal. Stopping criteria were based on day subject first met stopping criteria, using subject's diary data and asthma exacerbations recorded in CRF.
Day 1 to Day 84
Area Under The Curve From Time 0 Until The Last Measurable Concentration (AUC0-t) of Fp
Time Frame: Day 1: predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose
Approximately 20% of subjects randomized to the study and distributed across preselected study sites were to participate in fluticasone propionate pharmacokinetic assessments (the pharmacokinetic cohort). Subjects who had received fluticasone propionate in any form (orally, inhaled, or nasal) within 14 days of Day 1 were not permitted to participate in pharmacokinetic assessments.
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
Maximum Observed Plasma Concentration (Cmax) of Fp
Time Frame: Day 1: predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose
Approximately 20% of subjects randomized to the study and distributed across preselected study sites were to participate in fluticasone propionate pharmacokinetic assessments (the pharmacokinetic cohort). Subjects who had received fluticasone propionate in any form (orally, inhaled, or nasal) within 14 days of Day 1 were not permitted to participate in pharmacokinetic assessments.
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
Time of Maximum Concentration (Tmax) of Fp
Time Frame: Day 1: predose (within 10 minutes of treatment administration), and 5, 10, 15, 30, and 45 minutes, 1 hour, 1 hour 15 minutes, 1 hour 30 minutes, and 2, 4, 8, and 12 hours postdose
Approximately 20% of subjects randomized to the study and distributed across preselected study sites were to participate in fluticasone propionate pharmacokinetic assessments (the pharmacokinetic cohort). Subjects who had received fluticasone propionate in any form (orally, inhaled, or nasal) within 14 days of Day 1 were not permitted to participate in pharmacokinetic assessments.
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
Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
Time Frame: Day 1 -84
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 -84
Oropharyngeal Exam Findings at Each Study Visit
Time Frame: Screening (week -3 to -2), Baseline (Week 0), Weeks 1, 2, 4, 8, 12

Oropharyngeal examinations for visual evidence of oral candidiasis were conducted at all study visits. If the visual oropharyngeal examination was abnormal at the screening visit, the subject was excluded from entering the study and subjects with an abnormal oropharyngeal exam on Day 1 were not eligible for randomization. Any visual evidence of oral candidiasis during the treatment period of the study was evaluated by obtaining and analyzing a swab of the suspect area. 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. If a subject required a protocol-prohibited medication for therapy, the subject was to be discontinued from the study.

Data format: Time frame, <signs of oral candidiasis?> yes or no
Screening (week -3 to -2), Baseline (Week 0), Weeks 1, 2, 4, 8, 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline In Trough (Morning Predose And Pre-Rescue Bronchodilator) Forced Expiratory Volume In 1 Second (FEV1) Over The 12-Week Treatment Period Inclusive of Flovent Diskus Data
Time Frame: Baseline (Day 1, pre-dose), During Study (Days 7, 14, 28, 56 and 84 pre-dose)

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 including data from all treatments: change from baseline = baseline FEV1 + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
Baseline (Day 1, pre-dose), During Study (Days 7, 14, 28, 56 and 84 pre-dose)
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 Inclusive of Flovent Diskus Data
Time Frame: Baseline (Days -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)

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 including all treatments: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
Baseline (Days -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)
Change From Baseline In Weekly Average Of Daily Evening Peak Expiratory Flow (PEF) Over The 12-Week Treatment Period Inclusive of Flovent Diskus Data
Time Frame: Baseline (Days -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)

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 including all treatment groups: change from baseline = baseline PEF + sex + age + treatment + visit + treatment*visit with an unstructured covariance matrix assumed.
Baseline (Days -7 to 1, am pre-dose), During Study (Days 2-84 am pre-dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

Collaborators

PPD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

November 22, 2011

First Submitted That Met QC Criteria

November 23, 2011

First Posted (Estimate)

November 24, 2011

Study Record Updates

Last Update Posted (Actual)

June 5, 2017

Last Update Submitted That Met QC Criteria

May 2, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FpS-AS-201
  • 2010-023600-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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