Clinical trial NCT02139644: Study of Fluticasone Propionate MDPI Compared With Fluticasone/Salmeterol MDPI in Adolescent and Adult Patients With Persistent Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: fluticasone propionate
multidose dry powder inhaler
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 787
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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
measure: Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
timeFrame: Day 1 (predose, baseline), Week 12
Secondary outcomes:
measure: Change From Baseline in the Weekly Average of the Daily Morning Trough Peak Expiratory Flow (PEF) Over the 12 Week Treatment
timeFrame: Days -6 to Day 1 (predose), Day 1 (postdose) daily until Week 12
measure: Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over the 12-Week Treatment Period
timeFrame: Days -6 to Day 1 (predose, baseline) to Week 12
measure: 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
timeFrame: Days -6 to Day 1 (predose, baseline), up to week 12
measure: Kaplan-Meier Estimate of Probability of Remaining in Study At Week 12
timeFrame: up to Week 12 of the Treatment Period
measure: Change From Baseline in the Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ(S)) Score at Endpoint for Patients >=18 Years Old
timeFrame: Day 1 (predose, baseline), end of trial (up to week 12)
measure: Kaplan-Meier Estimates for Time to 15% and 12% Improvement From Baseline in FEV1 Postdose on Day 1
timeFrame: Day 1 of the Treatment Period (predose and postdose)
measure: Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
timeFrame: Day 1 to Week 12 of the Treatment Period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 12397
state: Alabama
city: Glendale
country: United States
facility: Teva Investigational Site 12375
state: Arizona
city: Cypress
country: United States
facility: Teva Investigational Site 12395
state: California
city: Encinitas
country: United States
facility: Teva Investigational Site 12476
state: California
city: Fountain Valley
country: United States
facility: Teva Investigational Site 12586
state: California
city: Fresno
country: United States
facility: Teva Investigational Site 12591
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 12372
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 12365
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 12381
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 12401
state: California
city: Mission Viejo
country: United States
facility: Teva Investigational Site 12394
state: California
city: Rancho Mirage
country: United States
facility: Teva Investigational Site 12490
state: California
city: Riverside
country: United States
facility: Teva Investigational Site 12393
state: California
city: Rolling Hills Estates
country: United States
facility: Teva Investigational Site 12366
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 12383
state: California
city: San Jose
country: United States
facility: Teva Investigational Site 12370
state: California
city: Stockton
country: United States
facility: Teva Investigational Site 12371
state: California
city: Upland
country: United States
facility: Teva Investigational Site 12579
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 12379
state: Colorado
city: Centennial
country: United States
facility: Teva Investigational Site 12386
state: Colorado
city: Colorado Springs
country: United States
facility: Teva Investigational Site 12596
state: Colorado
city: Longmont
country: United States
facility: Teva Investigational Site 12584
state: Colorado
city: Waterbury
country: United States
facility: Teva Investigational Site 12484
state: Connecticut
city: Waterbury
country: United States
facility: Teva Investigational Site 12590
state: Connecticut
city: Clearwater
country: United States
facility: Teva Investigational Site 12493
state: Florida
city: Largo
country: United States
facility: Teva Investigational Site 12992
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 12376
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 12390
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 12583
state: Florida
city: Tallahassee
country: United States
facility: Teva Investigational Site 12481
state: Florida
city: Winter Park
country: United States
facility: Teva Investigational Site 12491
state: Florida
city: Decatur
country: United States
facility: Teva Investigational Site 12997
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 12392
state: Georgia
city: Shiloh
country: United States
facility: Teva Investigational Site 12592
state: Illinois
city: Lenexa
country: United States
facility: Teva Investigational Site 12483
state: Kansas
city: Baltimore
country: United States
facility: Teva Investigational Site 12399
state: Maryland
city: Bethesda
country: United States
facility: Teva Investigational Site 12391
state: Maryland
city: Columbia
country: United States
facility: Teva Investigational Site 12589
state: Maryland
city: Rockville
country: United States
facility: Teva Investigational Site 12369
state: Maryland
city: Fall River
country: United States
facility: Teva Investigational Site 12396
state: Massachusetts
city: North Dartmouth
country: United States
facility: Teva Investigational Site 12384
state: Massachusetts
city: North Dartmouth
country: United States
facility: Teva Investigational Site 12585
state: Massachusetts
city: Ypsilanti
country: United States
facility: Teva Investigational Site 12588
state: Michigan
city: Saint Louis
country: United States
facility: Teva Investigational Site 12494
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 12595
state: Missouri
city: Missoula
country: United States
facility: Teva Investigational Site 12594
state: Montana
city: Ocean City
country: United States
facility: Teva Investigational Site 12385
state: New Jersey
city: Skillman
country: United States
facility: Teva Investigational Site 12380
state: New Jersey
city: Brooklyn
country: United States
facility: Teva Investigational Site 12587
state: New York
city: Rockville Centre
country: United States
facility: Teva Investigational Site 12485
state: New York
city: Huntersville
country: United States
facility: Teva Investigational Site 12475
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 12364
state: North Carolina
city: Canton
country: United States
facility: Teva Investigational Site 12374
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 12480
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 12492
state: Ohio
city: Middleburg Heights
country: United States
facility: Teva Investigational Site 12487
state: Ohio
city: Sylvania
country: United States
facility: Teva Investigational Site 12488
state: Ohio
city: Edmond
country: United States
facility: Teva Investigational Site 12377
state: Oklahoma
city: Medford
country: United States
facility: Teva Investigational Site 12368
state: Oregon
city: Portland
country: United States
facility: Teva Investigational Site 12382
state: Oregon
city: Pittsburgh
country: United States
facility: Teva Investigational Site 12400
state: Pennsylvania
city: Upland
country: United States
facility: Teva Investigational Site 12473
state: Pennsylvania
city: Greenville
country: United States
facility: Teva Investigational Site 12389
state: South Carolina
city: Mount Pleasant
country: United States
facility: Teva Investigational Site 12580
state: South Carolina
city: Orangeburg
country: United States
facility: Teva Investigational Site 12398
state: South Carolina
city: Knoxville
country: United States
facility: Teva Investigational Site 12991
state: Tennessee
city: Cypress
country: United States
facility: Teva Investigational Site 12990
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 12373
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 12402
state: Texas
city: New Braunfels
country: United States
facility: Teva Investigational Site 12582
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 12363
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 12482
state: Texas
city: Waco
country: United States
facility: Teva Investigational Site 12477
state: Texas
city: Murray
country: United States
facility: Teva Investigational Site 12478
state: Utah
city: South Burlington
country: United States
facility: Teva Investigational Site 12388
state: Vermont
city: Milwaukee
country: United States
facility: Teva Investigational Site 12378
state: Wisconsin
city: Toronto
country: Canada
facility: Teva Investigational Site 11065
state: Ontario
city: Montreal
country: Canada
facility: Teva Investigational Site 11067
state: Quebec
city: Vancouver
country: Canada
facility: Teva Investigational Site 11068
state: Quebec
city: Neratovice
country: Czechia
facility: Teva Investigational Site 54084
city: Praha
country: Czechia
facility: Teva Investigational Site 54088
city: Rokycany
country: Czechia
facility: Teva Investigational Site 54087
city: Budapest
country: Hungary
facility: Teva Investigational Site 51134
city: Budapest
country: Hungary
facility: Teva Investigational Site 51143
city: Budapest
country: Hungary
facility: Teva Investigational Site 51144
city: Debrecen
country: Hungary
facility: Teva Investigational Site 51140
city: Deszk
country: Hungary
facility: Teva Investigational Site 51142
city: Dombovar
country: Hungary
facility: Teva Investigational Site 51165
city: Kiskunhalas
country: Hungary
facility: Teva Investigational Site 51145
city: Miskolc
country: Hungary
facility: Teva Investigational Site 51141
city: Mosdós
country: Hungary
facility: Teva Investigational Site 51133
city: Nyíregyháza
country: Hungary
facility: Teva Investigational Site 51136
city: Nyíregyháza
country: Hungary
facility: Teva Investigational Site 51139
city: Sopron
country: Hungary
facility: Teva Investigational Site 51163
city: Szeged
country: Hungary
facility: Teva Investigational Site 51137
city: Szigetvár
country: Hungary
facility: Teva Investigational Site 51164
city: Szombathely
country: Hungary
facility: Teva Investigational Site 51138
city: Bialystok
country: Poland
facility: Teva Investigational Site 53182
city: Bialystok
country: Poland
facility: Teva Investigational Site 53183
city: Bialystok
country: Poland
facility: Teva Investigational Site 53185
city: Bialystok
country: Poland
facility: Teva Investigational Site 53191
city: Bienkówka
country: Poland
facility: Teva Investigational Site 53187
city: Bydgoszcz
country: Poland
facility: Teva Investigational Site 53219
city: Debica
country: Poland
facility: Teva Investigational Site 53217
city: Krakow
country: Poland
facility: Teva Investigational Site 53188
city: Kraków
country: Poland
facility: Teva Investigational Site 53178
city: Kraków
country: Poland
facility: Teva Investigational Site 53180
city: Lodz
country: Poland
facility: Teva Investigational Site 53220
city: Lodz
country: Poland
facility: Teva Investigational Site 53235
city: Lublin
country: Poland
facility: Teva Investigational Site 53237
city: Lódz
country: Poland
facility: Teva Investigational Site 53221
city: Poznan
country: Poland
facility: Teva Investigational Site 53194
city: Poznan
country: Poland
facility: Teva Investigational Site 53234
city: Strzelce Opolskie
country: Poland
facility: Teva Investigational Site 53233
city: Tarnów
country: Poland
facility: Teva Investigational Site 53179
city: Tarnów
country: Poland
facility: Teva Investigational Site 53218
city: Warszawa
country: Poland
facility: Teva Investigational Site 53193
city: Wroclaw
country: Poland
facility: Teva Investigational Site 53181
city: Wroclaw
country: Poland
facility: Teva Investigational Site 53189
city: Chelyabinsk
country: Russian Federation
facility: Teva Investigational Site 50236
city: Ekaterinburg
country: Russian Federation
facility: Teva Investigational Site 50226
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50227
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50234
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50238
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 50230
city: Saint Petersburg
country: Russian Federation
facility: Teva Investigational Site 50231
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 50224
city: Voronezh
country: Russian Federation
facility: Teva Investigational Site 50233
city: Yaroslavl
country: Russian Federation
facility: Teva Investigational Site 50237
city: Cape Town
country: South Africa
facility: Teva Investigational Site 90002
city: Cape Town
country: South Africa
facility: Teva Investigational Site 90008
city: Centurion
country: South Africa
facility: Teva Investigational Site 90005
city: Johannesburg
country: South Africa
facility: Teva Investigational Site 90001
city: Middelburg
country: South Africa
facility: Teva Investigational Site 90003
city: Pretoria
country: South Africa
facility: Teva Investigational Site 90007
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58125
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58126
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58127
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58128
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 58129
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.