Clinical trial NCT02141854: Efficacy and Safety Study of FP MDPI Compared With FS 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 Inhaled Corticosteroid Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-20
Enrollment: 882
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 (Fp) multidose dry powder inhaler (MDPI) and fluticasone propionate/salmeterol xinafoate (FS) MDPI when administered over 12 weeks in patients 12 years of age and older with persistent asthma.

Detailed description: Study drug and placebo were 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 qualifying dose of an inhaled corticosteroid (ICS). The 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 month 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 Institute 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 metered dose inhaler (MDI) device without a spacer device and a multidose dry powder inhaler (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 screening visit (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 hypercapnia, 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 AUEC0-12) 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, baseline), 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 12429
state: Alabama
city: Little Rock
country: United States
facility: Teva Investigational Site 12599
state: Alaska
city: Phoenix
country: United States
facility: Teva Investigational Site 12609
state: Arizona
city: Costa Mesa
country: United States
facility: Teva Investigational Site 12445
state: California
city: Encinitas
country: United States
facility: Teva Investigational Site 12454
state: California
city: Fresno
country: United States
facility: Teva Investigational Site 12456
state: California
city: Fullerton
country: United States
facility: Teva Investigational Site 12461
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 12410
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 12452
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 12417
state: California
city: Mission Viejo
country: United States
facility: Teva Investigational Site 13017
state: California
city: Rancho Mirage
country: United States
facility: Teva Investigational Site 12462
state: California
city: Rolling Hills Estates
country: United States
facility: Teva Investigational Site 12411
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 13018
state: California
city: San Jose
country: United States
facility: Teva Investigational Site 12413
state: California
city: Stockton
country: United States
facility: Teva Investigational Site 12403
state: California
city: Upland
country: United States
facility: Teva Investigational Site 12444
state: California
city: Vista
country: United States
facility: Teva Investigational Site 12999
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 12405
state: Colorado
city: Centennial
country: United States
facility: Teva Investigational Site 12419
state: Colorado
city: Colorado Springs
country: United States
facility: Teva Investigational Site 13000
state: Colorado
city: Waterbury
country: United States
facility: Teva Investigational Site 12459
state: Connecticut
city: Largo
country: United States
facility: Teva Investigational Site 13004
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 12414
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 12437
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 12427
state: Florida
city: Ormond Beach
country: United States
facility: Teva Investigational Site 12423
state: Florida
city: Panama City
country: United States
facility: Teva Investigational Site 12604
state: Florida
city: Tamarac
country: United States
facility: Teva Investigational Site 13316
state: Florida
city: Winter Park
country: United States
facility: Teva Investigational Site 12606
state: Florida
city: Savannah
country: United States
facility: Teva Investigational Site 12435
state: Georgia
city: Eagle
country: United States
facility: Teva Investigational Site 13315
state: Idaho
city: River Forest
country: United States
facility: Teva Investigational Site 12439
state: Illinois
city: Shiloh
country: United States
facility: Teva Investigational Site 12449
state: Illinois
city: South Bend
country: United States
facility: Teva Investigational Site 12457
state: Indiana
city: Bangor
country: United States
facility: Teva Investigational Site 12446
state: Maine
city: Columbia
country: United States
facility: Teva Investigational Site 12602
state: Maryland
city: Fall River
country: United States
facility: Teva Investigational Site 12432
state: Massachusetts
city: North Dartmouth
country: United States
facility: Teva Investigational Site 12441
state: Massachusetts
city: North Dartmouth
country: United States
facility: Teva Investigational Site 12466
state: Massachusetts
city: Royal Oak
country: United States
facility: Teva Investigational Site 13001
state: Michigan
city: Ypsilanti
country: United States
facility: Teva Investigational Site 12428
state: Michigan
city: Minneapolis
country: United States
facility: Teva Investigational Site 13020
state: Minnesota
city: Columbia
country: United States
facility: Teva Investigational Site 12451
state: Missouri
city: Rolla
country: United States
facility: Teva Investigational Site 12421
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 12412
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 12453
state: Missouri
city: Missoula
country: United States
facility: Teva Investigational Site 12610
state: Montana
city: Las Vegas
country: United States
facility: Teva Investigational Site 13021
state: Nevada
city: Skillman
country: United States
facility: Teva Investigational Site 12409
state: New Jersey
city: Bronx
country: United States
facility: Teva Investigational Site 12603
state: New York
city: Brooklyn
country: United States
facility: Teva Investigational Site 12464
state: New York
city: Charlotte
country: United States
facility: Teva Investigational Site 12430
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 12407
state: North Carolina
city: Canton
country: United States
facility: Teva Investigational Site 12415
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 12455
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 12463
state: Ohio
city: Middleburg Heights
country: United States
facility: Teva Investigational Site 12460
state: Ohio
city: Edmond
country: United States
facility: Teva Investigational Site 12426
state: Oklahoma
city: Oklahoma City
country: United States
facility: Teva Investigational Site 13008
state: Oklahoma
city: Medford
country: United States
facility: Teva Investigational Site 12406
state: Oregon
city: Portland
country: United States
facility: Teva Investigational Site 12442
state: Oregon
city: Normal
country: United States
facility: Teva Investigational Site 12563
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Teva Investigational Site 12443
state: Pennsylvania
city: Upland
country: United States
facility: Teva Investigational Site 12438
state: Pennsylvania
city: Charleston
country: United States
facility: Teva Investigational Site 12408
state: South Carolina
city: Greenville
country: United States
facility: Teva Investigational Site 12431
state: South Carolina
city: Mount Pleasant
country: United States
facility: Teva Investigational Site 12465
state: South Carolina
city: Mount Pleasant
country: United States
facility: Teva Investigational Site 12467
state: South Carolina
city: Orangeburg
country: United States
facility: Teva Investigational Site 12420
state: South Carolina
city: Rock Hill
country: United States
facility: Teva Investigational Site 12433
state: South Carolina
city: Knoxville
country: United States
facility: Teva Investigational Site 13003
state: Tennessee
city: Arlington
country: United States
facility: Teva Investigational Site 12425
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 12416
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 12418
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 12440
state: Texas
city: Killeen
country: United States
facility: Teva Investigational Site 12447
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13318
state: Texas
city: Sugar Land
country: United States
facility: Teva Investigational Site 13002
state: Texas
city: Waco
country: United States
facility: Teva Investigational Site 12424
state: Texas
city: South Burlington
country: United States
facility: Teva Investigational Site 12422
state: Vermont
city: Richmond
country: United States
facility: Teva Investigational Site 12605
state: Virginia
city: Spokane
country: United States
facility: Teva Investigational Site 12436
state: Washington
city: Tacoma
country: United States
facility: Teva Investigational Site 12564
state: Washington
city: Greenfield
country: United States
facility: Teva Investigational Site 12448
state: Wisconsin
city: Toronto
country: Canada
facility: Teva Investigational Site 11072
state: Ontario
city: Vancouver
country: Canada
facility: Teva Investigational Site 11075
state: Quebec
city: Jindrichuv Hradec
country: Czechia
facility: Teva Investigational Site 54096
city: Praha
country: Czechia
facility: Teva Investigational Site 54098
city: Rokycany
country: Czechia
facility: Teva Investigational Site 54095
city: Strakonice
country: Czechia
facility: Teva Investigational Site 54094
city: Budapest
country: Hungary
facility: Teva Investigational Site 51149
city: Budapest
country: Hungary
facility: Teva Investigational Site 51155
city: Budapest
country: Hungary
facility: Teva Investigational Site 51157
city: Budapest
country: Hungary
facility: Teva Investigational Site 51161
city: Debrecen
country: Hungary
facility: Teva Investigational Site 51154
city: Deszk
country: Hungary
facility: Teva Investigational Site 51152
city: Dombovar
country: Hungary
facility: Teva Investigational Site 51170
city: Kiskunhalas
country: Hungary
facility: Teva Investigational Site 51158
city: Miskolc
country: Hungary
facility: Teva Investigational Site 51153
city: Mosdós
country: Hungary
facility: Teva Investigational Site 51156
city: Nyíregyháza
country: Hungary
facility: Teva Investigational Site 51150
city: Nyíregyháza
country: Hungary
facility: Teva Investigational Site 51151
city: Szeged
country: Hungary
facility: Teva Investigational Site 51146
city: Szigetvár
country: Hungary
facility: Teva Investigational Site 51162
city: Szombathely
country: Hungary
facility: Teva Investigational Site 51147
city: Százhalombatta
country: Hungary
facility: Teva Investigational Site 51148
city: Tatabánya
country: Hungary
facility: Teva Investigational Site 51176
city: Törökbálint
country: Hungary
facility: Teva Investigational Site 51177
city: Bialystok
country: Poland
facility: Teva Investigational Site 53199
city: Bialystok
country: Poland
facility: Teva Investigational Site 53200
city: Bialystok
country: Poland
facility: Teva Investigational Site 53202
city: Bialystok
country: Poland
facility: Teva Investigational Site 53208
city: Bydgoszcz
country: Poland
facility: Teva Investigational Site 53210
city: Bydgoszcz
country: Poland
facility: Teva Investigational Site 53227
city: Debica
country: Poland
facility: Teva Investigational Site 53225
city: Gdansk
country: Poland
facility: Teva Investigational Site 53203
city: Krakow
country: Poland
facility: Teva Investigational Site 53205
city: Kraków
country: Poland
facility: Teva Investigational Site 53195
city: Kraków
country: Poland
facility: Teva Investigational Site 53197
city: Lodz
country: Poland
facility: Teva Investigational Site 53228
city: Lodz
country: Poland
facility: Teva Investigational Site 53240
city: Lublin
country: Poland
facility: Teva Investigational Site 53241
city: Lódz
country: Poland
facility: Teva Investigational Site 53201
city: Lódz
country: Poland
facility: Teva Investigational Site 53229
city: Poznan
country: Poland
facility: Teva Investigational Site 53206
city: Poznan
country: Poland
facility: Teva Investigational Site 53211
city: Strzelce Opolskie
country: Poland
facility: Teva Investigational Site 53230
city: Tarnów
country: Poland
facility: Teva Investigational Site 53196
city: Warszawa
country: Poland
facility: Teva Investigational Site 53222
city: Wroclaw
country: Poland
facility: Teva Investigational Site 53198
city: Wroclaw
country: Poland
facility: Teva Investigational Site 53224
city: Chelyabinsk
country: Russian Federation
facility: Teva Investigational Site 50255
city: Ekaterinburg
country: Russian Federation
facility: Teva Investigational Site 50243
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50241
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50250
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50252
city: Saint Petersburg
country: Russian Federation
facility: Teva Investigational Site 50246
city: Saint-Petersburg
country: Russian Federation
facility: Teva Investigational Site 50242
city: Saratov
country: Russian Federation
facility: Teva Investigational Site 50254
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 50245
city: Tomsk
country: Russian Federation
facility: Teva Investigational Site 50244
city: Voronezh
country: Russian Federation
facility: Teva Investigational Site 50251
city: Yaroslavl
country: Russian Federation
facility: Teva Investigational Site 50275
city: Berea
country: South Africa
facility: Teva Investigational Site 90011
city: Bloemfontein
country: South Africa
facility: Teva Investigational Site 90015
city: Cape Town
country: South Africa
facility: Teva Investigational Site 90012
city: Centurion
country: South Africa
facility: Teva Investigational Site 90013
city: Middelburg
country: South Africa
facility: Teva Investigational Site 90016
city: Pretoria
country: South Africa
facility: Teva Investigational Site 90014
city: Papillion
country: Thailand
facility: Teva Investigational Site 12404
state: NE
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58133
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58135
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58132
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Sher LD, Yiu G, Sakov A, Liu S, Caracta CF. Fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers compared with placebo for persistent asthma. Allergy Asthma Proc. 2017 Sep 21;38(5):343-353. doi: 10.2500/aap.2017.38.4069. Epub 2017 Jun 21.
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.