Study of Fluticasone Propionate MDPI Compared With Fluticasone/Salmeterol MDPI in Adolescent and Adult Patients With Persistent Asthma

A 12-Week, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Fluticasone Propionate Multidose Dry Powder Inhaler Compared With Fluticasone/Salmeterol Multidose Dry Powder Inhaler in Adolescent and Adult Patients With Persistent Asthma Symptomatic Despite Low-dose or or Mid-dose Inhaled Corticosteroid Therapy

The primary objective of this study was to evaluate the efficacy of fluticasone propionate multidose dry powder inhaler (Fp MDPI) and fluticasone propionate/salmeterol xinafoate multidose dry powder inhaler (FS MDPI) when administered over 12 weeks in patients 12 years of age and older with persistent asthma.

Study drug and placebo was supplied in Teva multidose dry powder inhaler (MDPI) devices and provided for participants to use at home. Participants performed spirometry at every visit. Each participant was given a diary at each visit for use until the next visit. Rescue medication (albuterol/salbutamol) was dispensed at each visit, if needed, as determined by the investigational center personnel.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: FS MDPI; Drug: albuterol/salbutamol; Drug: Beclomethasone dipropionate; Drug: Fp MDPI; Drug: Placebo MDPI

• Study Type: Interventional
• Enrollment (Actual): 787
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Teva Investigational Site 11065
  • Quebec
    • Montreal, Quebec, Canada
      • Teva Investigational Site 11067
    • Vancouver, Quebec, Canada
      • Teva Investigational Site 11068
• Czechia
  • Neratovice, Czechia
    • Teva Investigational Site 54084
  • Praha, Czechia
    • Teva Investigational Site 54088
  • Rokycany, Czechia
    • Teva Investigational Site 54087
• Hungary
  • Budapest, Hungary
    • Teva Investigational Site 51134
  • Budapest, Hungary
    • Teva Investigational Site 51143
  • Budapest, Hungary
    • Teva Investigational Site 51144
  • Debrecen, Hungary
    • Teva Investigational Site 51140
  • Deszk, Hungary
    • Teva Investigational Site 51142
  • Dombovar, Hungary
    • Teva Investigational Site 51165
  • Kiskunhalas, Hungary
    • Teva Investigational Site 51145
  • Miskolc, Hungary
    • Teva Investigational Site 51141
  • Mosdós, Hungary
    • Teva Investigational Site 51133
  • Nyíregyháza, Hungary
    • Teva Investigational Site 51136
  • Nyíregyháza, Hungary
    • Teva Investigational Site 51139
  • Sopron, Hungary
    • Teva Investigational Site 51163
  • Szeged, Hungary
    • Teva Investigational Site 51137
  • Szigetvár, Hungary
    • Teva Investigational Site 51164
  • Szombathely, Hungary
    • Teva Investigational Site 51138
• Poland
  • Bialystok, Poland
    • Teva Investigational Site 53182
  • Bialystok, Poland
    • Teva Investigational Site 53183
  • Bialystok, Poland
    • Teva Investigational Site 53185
  • Bialystok, Poland
    • Teva Investigational Site 53191
  • Bienkówka, Poland
    • Teva Investigational Site 53187
  • Bydgoszcz, Poland
    • Teva Investigational Site 53219
  • Debica, Poland
    • Teva Investigational Site 53217
  • Krakow, Poland
    • Teva Investigational Site 53188
  • Kraków, Poland
    • Teva Investigational Site 53178
  • Kraków, Poland
    • Teva Investigational Site 53180
  • Lodz, Poland
    • Teva Investigational Site 53220
  • Lodz, Poland
    • Teva Investigational Site 53235
  • Lublin, Poland
    • Teva Investigational Site 53237
  • Lódz, Poland
    • Teva Investigational Site 53221
  • Poznan, Poland
    • Teva Investigational Site 53194
  • Poznan, Poland
    • Teva Investigational Site 53234
  • Strzelce Opolskie, Poland
    • Teva Investigational Site 53233
  • Tarnów, Poland
    • Teva Investigational Site 53179
  • Tarnów, Poland
    • Teva Investigational Site 53218
  • Warszawa, Poland
    • Teva Investigational Site 53193
  • Wroclaw, Poland
    • Teva Investigational Site 53181
  • Wroclaw, Poland
    • Teva Investigational Site 53189
• Russian Federation
  • Chelyabinsk, Russian Federation
    • Teva Investigational Site 50236
  • Ekaterinburg, Russian Federation
    • Teva Investigational Site 50226
  • Kazan, Russian Federation
    • Teva Investigational Site 50227
  • Moscow, Russian Federation
    • Teva Investigational Site 50234
  • Moscow, Russian Federation
    • Teva Investigational Site 50238
  • Novosibirsk, Russian Federation
    • Teva Investigational Site 50230
  • Saint Petersburg, Russian Federation
    • Teva Investigational Site 50231
  • St. Petersburg, Russian Federation
    • Teva Investigational Site 50224
  • Voronezh, Russian Federation
    • Teva Investigational Site 50233
  • Yaroslavl, Russian Federation
    • Teva Investigational Site 50237
• South Africa
  • Cape Town, South Africa
    • Teva Investigational Site 90002
  • Cape Town, South Africa
    • Teva Investigational Site 90008
  • Centurion, South Africa
    • Teva Investigational Site 90005
  • Johannesburg, South Africa
    • Teva Investigational Site 90001
  • Middelburg, South Africa
    • Teva Investigational Site 90003
  • Pretoria, South Africa
    • Teva Investigational Site 90007
• Ukraine
  • Kharkiv, Ukraine
    • Teva Investigational Site 58125
  • Kharkiv, Ukraine
    • Teva Investigational Site 58126
  • Kyiv, Ukraine
    • Teva Investigational Site 58127
  • Kyiv, Ukraine
    • Teva Investigational Site 58128
  • Vinnytsya, Ukraine
    • Teva Investigational Site 58129
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Teva Investigational Site 12397
  • Arizona
    • Glendale, Arizona, United States
      • Teva Investigational Site 12375
  • California
    • Cypress, California, United States
      • Teva Investigational Site 12395
    • Encinitas, California, United States
      • Teva Investigational Site 12476
    • Fountain Valley, California, United States
      • Teva Investigational Site 12586
    • Fresno, California, United States
      • Teva Investigational Site 12591
    • Huntington Beach, California, United States
      • Teva Investigational Site 12372
    • Los Angeles, California, United States
      • Teva Investigational Site 12365
    • Los Angeles, California, United States
      • Teva Investigational Site 12381
    • Los Angeles, California, United States
      • Teva Investigational Site 12401
    • Mission Viejo, California, United States
      • Teva Investigational Site 12394
    • Rancho Mirage, California, United States
      • Teva Investigational Site 12490
    • Riverside, California, United States
      • Teva Investigational Site 12393
    • Rolling Hills Estates, California, United States
      • Teva Investigational Site 12366
    • San Diego, California, United States
      • Teva Investigational Site 12383
    • San Jose, California, United States
      • Teva Investigational Site 12370
    • Stockton, California, United States
      • Teva Investigational Site 12371
    • Upland, California, United States
      • Teva Investigational Site 12579
  • Colorado
    • Centennial, Colorado, United States
      • Teva Investigational Site 12379
    • Centennial, Colorado, United States
      • Teva Investigational Site 12386
    • Colorado Springs, Colorado, United States
      • Teva Investigational Site 12596
    • Longmont, Colorado, United States
      • Teva Investigational Site 12584
  • Connecticut
    • Waterbury, Connecticut, United States
      • Teva Investigational Site 12484
    • Waterbury, Connecticut, United States
      • Teva Investigational Site 12590
  • Florida
    • Clearwater, Florida, United States
      • Teva Investigational Site 12493
    • Largo, Florida, United States
      • Teva Investigational Site 12992
    • Miami, Florida, United States
      • Teva Investigational Site 12376
    • Miami, Florida, United States
      • Teva Investigational Site 12390
    • Orlando, Florida, United States
      • Teva Investigational Site 12583
    • Tallahassee, Florida, United States
      • Teva Investigational Site 12481
    • Winter Park, Florida, United States
      • Teva Investigational Site 12491
  • Georgia
    • Decatur, Georgia, United States
      • Teva Investigational Site 12997
    • Savannah, Georgia, United States
      • Teva Investigational Site 12392
  • Illinois
    • Shiloh, Illinois, United States
      • Teva Investigational Site 12592
  • Kansas
    • Lenexa, Kansas, United States
      • Teva Investigational Site 12483
  • Maryland
    • Baltimore, Maryland, United States
      • Teva Investigational Site 12399
    • Bethesda, Maryland, United States
      • Teva Investigational Site 12391
    • Columbia, Maryland, United States
      • Teva Investigational Site 12589
    • Rockville, Maryland, United States
      • Teva Investigational Site 12369
  • Massachusetts
    • Fall River, Massachusetts, United States
      • Teva Investigational Site 12396
    • North Dartmouth, Massachusetts, United States
      • Teva Investigational Site 12384
    • North Dartmouth, Massachusetts, United States
      • Teva Investigational Site 12585
  • Michigan
    • Ypsilanti, Michigan, United States
      • Teva Investigational Site 12588
  • Missouri
    • Saint Louis, Missouri, United States
      • Teva Investigational Site 12494
    • Saint Louis, Missouri, United States
      • Teva Investigational Site 12595
  • Montana
    • Missoula, Montana, United States
      • Teva Investigational Site 12594
  • New Jersey
    • Ocean City, New Jersey, United States
      • Teva Investigational Site 12385
    • Skillman, New Jersey, United States
      • Teva Investigational Site 12380
  • New York
    • Brooklyn, New York, United States
      • Teva Investigational Site 12587
    • Rockville Centre, New York, United States
      • Teva Investigational Site 12485
  • North Carolina
    • Huntersville, North Carolina, United States
      • Teva Investigational Site 12475
    • Raleigh, North Carolina, United States
      • Teva Investigational Site 12364
  • Ohio
    • Canton, Ohio, United States
      • Teva Investigational Site 12374
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 12480
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 12492
    • Middleburg Heights, Ohio, United States
      • Teva Investigational Site 12487
    • Sylvania, Ohio, United States
      • Teva Investigational Site 12488
  • Oklahoma
    • Edmond, Oklahoma, United States
      • Teva Investigational Site 12377
  • Oregon
    • Medford, Oregon, United States
      • Teva Investigational Site 12368
    • Portland, Oregon, United States
      • Teva Investigational Site 12382
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Teva Investigational Site 12400
    • Upland, Pennsylvania, United States
      • Teva Investigational Site 12473
  • South Carolina
    • Greenville, South Carolina, United States
      • Teva Investigational Site 12389
    • Mount Pleasant, South Carolina, United States
      • Teva Investigational Site 12580
    • Orangeburg, South Carolina, United States
      • Teva Investigational Site 12398
  • Tennessee
    • Knoxville, Tennessee, United States
      • Teva Investigational Site 12991
  • Texas
    • Cypress, Texas, United States
      • Teva Investigational Site 12990
    • Dallas, Texas, United States
      • Teva Investigational Site 12373
    • El Paso, Texas, United States
      • Teva Investigational Site 12402
    • New Braunfels, Texas, United States
      • Teva Investigational Site 12582
    • San Antonio, Texas, United States
      • Teva Investigational Site 12363
    • San Antonio, Texas, United States
      • Teva Investigational Site 12482
    • Waco, Texas, United States
      • Teva Investigational Site 12477
  • Utah
    • Murray, Utah, United States
      • Teva Investigational Site 12478
  • Vermont
    • South Burlington, Vermont, United States
      • Teva Investigational Site 12388
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Teva Investigational Site 12378

Participation Criteria

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. Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of their predicted normal value.
2. Current Asthma Therapy: Patients must have a short-acting β2-agonist (for rescue use) for a minimum of 8 weeks before the Screening Visit (SV) and a low-dose inhaled corticosteroid (ICS). The low-dose ICS may be either as ICS monotherapy or as an ICS/long-acting beta agonist (LABA) combination. The ICS component of the patient's asthma therapy should be stable for a minimum of 1 months before providing consent.
3. Reversibility of Disease: Patients must have at least 15% reversibility (all patients) and at least a 200 mL increase from baseline FEV1 (patients age 18 and older) within 30 minutes after 2 to 4 inhalations of albuterol/salbutamol at the SV. Note: Patients who do not qualify for the study due to failure to meet reversibility will be permitted to perform a retest once within 7 days.
4. Patients must provide written informed consent/assent. For minor patients (ages 12 to 17 years, or as applicable per local regulations), the written ICF must be signed and dated by the parent/legal guardian and the written assent form must be signed and dated by the patient (if applicable). Note: Age requirements are as specified by local regulations.
5. Outpatient >= 12 years of age on the date of consent/assent. In countries where the local regulations permit enrollment of adult patients only, patients must be 18 years of age and older.
6. Asthma diagnosis: The patient has a diagnosis of asthma as defined by the National Institutes of Health (NIH). The asthma diagnosis has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in asthma medication) for at least 30 days.
7. The patient is able to perform acceptable and repeatable spirometry.
8. The patient is able to perform peak expiratory flow (PEF) with a handheld peak flow meter.
9. The patient is able to use a MDI device without a spacer device and a MDPI device.
10. The patient is able to withhold (as judged by the investigator) his or her regimen of ICS or study drug, and rescue medication for at least 6 hours before the SV and before all treatment visits.
11. The patient/parent/legal guardian/caregiver is 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.
12. SABAs: All patients must be able to replace their current SABA with albuterol/salbutamol HFA MDI inhalation aerosol for the duration of the study.

13. Female patients may not be pregnant, breastfeeding, or attempting to become pregnant.

    • other criteria may apply, please contact the investigator for more information

Exclusion Criteria:

1. A history of a life-threatening asthma exacerbation (an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures).
2. The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the study.
3. The patient has participated as a randomized patient in any investigational drug study within 30 days of the SV.
4. The patient has previously participated as a randomized patient in a study of Fp MDPI or FS MDPI.
5. The patient has a known hypersensitivity to any corticosteroid, salmeterol, or any of the excipients in the study drug or rescue medication formulation (ie, lactose).
6. The patient has been treated with any known strong cytochrome P450 (CYP) 3A4 inhibitors (eg, azole antifungals, ritonavir, or clarithromycin) within 30 days before the SV.
7. The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before the SV.
8. The patient currently smokes or has a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient must not have used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco).
9. The patient has a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the SV.
10. The patient has a history of alcohol or drug abuse within 2 years preceding the SV.
11. The patient has had an asthma exacerbation requiring systemic corticosteroids within 30 days before the SV, or has had any hospitalization for asthma within 2 months before the SV.
12. Initiation or dose escalation of immunotherapy (administered by any route) is planned during the study period. However, patients on stable immunotherapy may be considered for inclusion.
13. The patient has used immunosuppressive medications within 4 weeks before the SV.
14. The patient is unable to tolerate or unwilling to comply with the appropriate washout periods and withholding of all applicable medications.
15. The patient has untreated oral candidiasis at the SV. Patients with clinical visual evidence of oral candidiasis who agree to receive treatment and comply with appropriate medical monitoring may enter the study.
16. The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection.
17. The patient is either an employee or an immediate relative of an employee of the clinical investigational center.
18. A member of the patient's household is participating in the study at the same time. However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened.

19. The patient has a disease/condition that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study.

    • other criteria may apply, please contact the investigator for more information

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FS MDPI 100 / 12.5 mcg; Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.	Drug: FS MDPI; FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) and salmeterol xinafoate (Sx) 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 either 100/12.5 mcg Fp/Sx or 50/12.5 mcg Fp/Sx in the morning and evening for a total daily dose of 200/25 mcg or 100/25 mcg Fp/Sx. Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.; Other Names: fluticasone propionate; inhaled corticosteroid; β2 adrenoceptor agonist; salmeterol xinafoate; 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: Beclomethasone dipropionate; QVAR (beclomethasone dipropionate) 40 mcg inhalation aerosol is a pressurized MDI that contains a Food and Drug Administration (FDA)-approved formulation of beclomethasone dipropionate. Patients took 1 puff twice a day from open-label QVAR 40 mcg hydrofluoroalkane (specifically, HFA-134a) metered-dose inhaler (MDI) for the duration of the Run-in Period (14-21 days) and prior to randomization. A clinically equivalent dose of inhaled corticosteroid (ICS) was substituted in countries where QVAR 40 mcg was not available.; Other Names: QVAR
Experimental: FS MDPI 50 / 12.5 mcg; Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.	Drug: FS MDPI; FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) and salmeterol xinafoate (Sx) 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 either 100/12.5 mcg Fp/Sx or 50/12.5 mcg Fp/Sx in the morning and evening for a total daily dose of 200/25 mcg or 100/25 mcg Fp/Sx. Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.; Other Names: fluticasone propionate; inhaled corticosteroid; β2 adrenoceptor agonist; salmeterol xinafoate; 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: Beclomethasone dipropionate; QVAR (beclomethasone dipropionate) 40 mcg inhalation aerosol is a pressurized MDI that contains a Food and Drug Administration (FDA)-approved formulation of beclomethasone dipropionate. Patients took 1 puff twice a day from open-label QVAR 40 mcg hydrofluoroalkane (specifically, HFA-134a) metered-dose inhaler (MDI) for the duration of the Run-in Period (14-21 days) and prior to randomization. A clinically equivalent dose of inhaled corticosteroid (ICS) was substituted in countries where QVAR 40 mcg was not available.; Other Names: QVAR
Experimental: Fp MDPI 100 mcg; Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg for a total daily dose of 200 mcg for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.	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: Beclomethasone dipropionate; QVAR (beclomethasone dipropionate) 40 mcg inhalation aerosol is a pressurized MDI that contains a Food and Drug Administration (FDA)-approved formulation of beclomethasone dipropionate. Patients took 1 puff twice a day from open-label QVAR 40 mcg hydrofluoroalkane (specifically, HFA-134a) metered-dose inhaler (MDI) for the duration of the Run-in Period (14-21 days) and prior to randomization. A clinically equivalent dose of inhaled corticosteroid (ICS) was substituted in countries where QVAR 40 mcg was not available.; Other Names: QVAR; Drug: Fp MDPI; Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate 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 either 100 mcg or 50 mcg of Fp one inhalation twice a day for a total daily dose of 200 mcg or 100 mcg. Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.; Other Names: fluticasone propionate; inhaled corticosteroid
Experimental: Fp MDPI 50 mcg; Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg for a total daily dose of 100 mcg for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.	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: Beclomethasone dipropionate; QVAR (beclomethasone dipropionate) 40 mcg inhalation aerosol is a pressurized MDI that contains a Food and Drug Administration (FDA)-approved formulation of beclomethasone dipropionate. Patients took 1 puff twice a day from open-label QVAR 40 mcg hydrofluoroalkane (specifically, HFA-134a) metered-dose inhaler (MDI) for the duration of the Run-in Period (14-21 days) and prior to randomization. A clinically equivalent dose of inhaled corticosteroid (ICS) was substituted in countries where QVAR 40 mcg was not available.; Other Names: QVAR; Drug: Fp MDPI; Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate 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 either 100 mcg or 50 mcg of Fp one inhalation twice a day for a total daily dose of 200 mcg or 100 mcg. Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.; Other Names: fluticasone propionate; inhaled corticosteroid
Placebo Comparator: Placebo MDPI; The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart). Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.	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: Beclomethasone dipropionate; QVAR (beclomethasone dipropionate) 40 mcg inhalation aerosol is a pressurized MDI that contains a Food and Drug Administration (FDA)-approved formulation of beclomethasone dipropionate. Patients took 1 puff twice a day from open-label QVAR 40 mcg hydrofluoroalkane (specifically, HFA-134a) metered-dose inhaler (MDI) for the duration of the Run-in Period (14-21 days) and prior to randomization. A clinically equivalent dose of inhaled corticosteroid (ICS) was substituted in countries where QVAR 40 mcg was not available.; Other Names: QVAR; Drug: Placebo MDPI; Placebo administered via a multidose dry powder inhaler (MDPI) one puff in the morning and one puff in the evening for 12 weeks.; Other Names: inert powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standardized Baseline-Adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time Zero to 12 Hours Postdose (FEV1 AUEC0-12h) at Week 12	A subset of approximately 300 patients who performed postdose serial spirometry is based on sample size calculation. Data from these assessments were used to analyze the primary endpoint of baseline adjusted FEV1 AUEC0-12h at week 12 using the trapezoidal rule based on actual time of measurement. It was standardized by dividing it by the number of hours between the start time of dose administration and the end time of the last nonmissing FEV1 measurement. The baseline FEV1 was the average of the 2 predose FEV1 measurements (30 and 10 minutes predose). If 1 of these was missing, the nonmissing value was used; if both were missing, baseline was treated as missing. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting the baseline FEV1 value.	Day 1 (predose, baseline), Week 12 and was performed at the following times relative to the administration of study drug (±5 minutes): 15 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, and 12 hours
Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12	Trough FEV1 was a morning spirometry taken predose and pre-rescue bronchodilator. If the patient inadvertently administered asthma medication/study drug at home on the AM of the visit, or if the patient took rescue medication within 6 hours of testing, the visit was rescheduled. The baseline for predose FEV1 was defined as the average of the 30-minute and 10-minute predose measurements obtained at the randomization visit (Day 1).	Day 1 (predose, baseline), Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Weekly Average of the Daily Morning Trough Peak Expiratory Flow (PEF) Over the 12 Week Treatment	Morning PEF tests were performed before administration of study drug or rescue medications (data were excluded if the time of PEF measurement was more than 5 minutes after the dose time). The patient recorded the highest value of 3 measurements obtained in the patient diary. The baseline PEF was the average value of recorded (nonmissing) morning assessments over the 7 days prior to randomization on Day 1. For efficacy analyses of weekly average morning PEF measurements, values were the averages based on available data for that week.	Days -6 to Day 1 (predose), Day 1 (postdose) daily until Week 12
Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over the 12-Week Treatment Period	The total daily asthma symptom score is the average of the daytime and nighttime scores as recorded in the patient diary (range 0-9). Daytime Symptom Score: 0=No symptoms; Symptoms for 1 short period; Symptoms for 2+ short periods; Symptoms for most of the day - did not affect normal daily activities; Symptoms for most of the day - did affect normal daily activities; Symptoms so severe that I could not go to work or perform normal daily activities Nighttime Symptom Score (determined in the AM): 0=No symptoms; Symptoms causing me to wake once (or wake early); Symptoms causing me to wake twice or more (including waking early); Symptoms causing me to be awake for most of the night; Symptoms so severe that I did not sleep Baseline was the average of recorded scores over the 7 days before randomization. The change from baseline in the weekly average over weeks 1 to 12 was analyzed using an mixed model for repeated measures (MMRM).	Days -6 to Day 1 (predose, baseline) to Week 12
Change From Baseline in the Weekly Average of the Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol Over the 12-Week Treatment Period	Patients recorded the number of inhalations of rescue medication (albuterol/salbutamol HFA MDI) each AM and PM in the diary. The average number of daily inhalations over the 7 days before the randomization visit was the baseline value. The weekly average was based on the available data for the 7 days before each analysis week. The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using a mixed model for repeated measures.	Days -6 to Day 1 (predose, baseline), up to week 12
Kaplan-Meier Estimate of Probability of Remaining in 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, defined as the number of days elapsed from the date of randomization to the date of withdrawal due to worsening asthma. Patients who were lost to follow-up, who had not withdrawn due to worsening asthma by week 12, or who had withdrawn due to reasons other than worsening asthma were right-censored at the date of last assessment.	up to Week 12 of the Treatment Period
Change From Baseline in the Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ(S)) Score at Endpoint for Patients >=18 Years Old	The AQLQ(S) (September 2010 version; patients aged ≥18 years) was self-administered by the patients at the investigational center at the randomization visit and at Week 12 or end of trial. The questionnaire is a tool to measure the impact of asthma on a patient's quality of life (physical, emotional, social, and occupational) with a recall period of 2 weeks. The AQLQ(S) was administered only to patients 18 years and older. The 32 individual questions in the AQLQ were equally weighted. The overall AQLQ score was the mean of the responses to each of the 32 questions, and ranged from 1 to 7. A score of 7.0 indicated that the patient had no impairments due to asthma and a score of 1.0 indicated severe impairment. Positive change from baseline scores indicate improved quality of life.	Day 1 (predose, baseline), end of trial (up to week 12)
Kaplan-Meier Estimates for Time to 15% and 12% Improvement From Baseline in FEV1 Postdose on Day 1	A subset of approximately 300 patients who performed postdose serial spirometry is based on sample size calculation. Baseline FEV1 was the average of 2 FEV1 measurements (30 and 10 minutes predose) on Day 1. If one of these was missing, the other measurement was used as baseline value. If both were missing, baseline was treated as missing. Time to target improvement (15% or 12%) was defined as the time elapsed from the time of first dose to the first time the target improvement in FEV1 was achieved. If an exact target increase was not achieved at a measured timepoint, then the time was estimated by linear interpolation between the timepoint when target was reached and the timepoint immediately before. Patients who did not achieve the target improvement were censored at the time of last serial spirometry assessment. Values of 9999 indicate the values could not be estimated which happened when the estimated probability of not achieving target is more than 50%.	Day 1 of the Treatment Period (predose and postdose)
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 of the Treatment Period

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• Miller DS, Yiu G, Hellriegel ET, Steinfeld J. Dose-ranging study of salmeterol using a novel fluticasone propionate/salmeterol multidose dry powder inhaler in patients with persistent asthma. Allergy Asthma Proc. 2016 Jul;37(4):291-301. doi: 10.2500/aap.2016.37.3963. Epub 2016 May 27.
• Raphael G, Yiu G, Sakov A, Liu S, Caracta C. Randomized, double-blind trial evaluating the efficacy and safety of fluticasone propionate and fluticasone propionate/salmeterol delivered via multidose dry powder inhalers in patients with persistent asthma aged 12 years and older. J Asthma. 2018 Jun;55(6):640-650. doi: 10.1080/02770903.2017.1350971. Epub 2017 Aug 31.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): November 12, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: fluticasone propionate; multidose dry powder inhaler
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Fluticasone; Xhance; Albuterol; Salmeterol Xinafoate; Adrenergic Agonists; Beclomethasone
• Other Study ID Numbers: FSS-AS-301; 2014-001149-25 (EudraCT Number)