AsthmaPhase 3NCT02141854
Efficacy and Safety Study of FP MDPI Compared With FS MDPI in Adolescent and Adult Patients With Persistent Asthma
A Phase 3 study testing FS MDPI, Fp MDPI and Albuterol/salmeterol HFA MDI in people with Asthma, run by Teva Branded Pharmaceutical Products R&D, Inc. at 154 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- FS MDPI, Fp MDPI and Albuterol/salmeterol HFA MDI
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 882 participants
- Where
- 154 sitesin 9 countries
- Study dates
- Jun 2014to Sep 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of their predicted normal value.
- 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.
- 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.
- 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.
- 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.
- 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.
Show all 14Show fewer
- The patient is able to perform acceptable and repeatable spirometry.
- The patient is able to perform peak expiratory flow (PEF) with a handheld peak flow meter.
- The patient is able to use a metered dose inhaler (MDI) device without a spacer device and a multidose dry powder inhaler (MDPI) device.
- 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.
- 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.
- SABAs: All patients must be able to replace their current SABA with albuterol/salbutamol HFA MDI inhalation aerosol for the duration of the study.
- Female patients may not be pregnant, breastfeeding, or attempting to become pregnant.
- other criteria may apply, please contact the investigator for more information
Who cannot join
- 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).
- The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the study.
- The patient has participated as a randomized patient in any investigational drug study within 30 days of the SV.
- The patient has previously participated as a randomized patient in a study of Fp MDPI or FS MDPI.
- 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).
- 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.
Show all 20Show fewer
- The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before the SV.
- 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).
- 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.
- The patient has a history of alcohol or drug abuse within 2 years preceding the SV.
- 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.
- 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.
- The patient has used immunosuppressive medications within 4 weeks before the SV.
- The patient is unable to tolerate or unwilling to comply with the appropriate washout periods and withholding of all applicable medications.
- 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.
- The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection.
- The patient is either an employee or an immediate relative of an employee of the clinical investigational center.
- 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.
- 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
Trial locations and contacts
154 sites in 9 countries.
154 sites in 9 countries
United States85 sites
Teva Investigational Site 12425
Arlington, Texas
Teva Investigational Site 12446
Bangor, Maine
Teva Investigational Site 12429
Birmingham, Alabama
Teva Investigational Site 12464
Brooklyn, New York
Teva Investigational Site 12415
Canton, Ohio
Teva Investigational Site 12405
Centennial, Colorado
Teva Investigational Site 12419
Centennial, Colorado
Teva Investigational Site 12408
Charleston, South Carolina
Teva Investigational Site 12430
Charlotte, North Carolina
Teva Investigational Site 12455
Cincinnati, Ohio
Teva Investigational Site 12463
Cincinnati, Ohio
Teva Investigational Site 13000
Colorado Springs, Colorado
Teva Investigational Site 12602
Columbia, Maryland
Teva Investigational Site 12451
Columbia, Missouri
Teva Investigational Site 12445
Costa Mesa, California
Teva Investigational Site 12416
Dallas, Texas
Teva Investigational Site 12418
Dallas, Texas
Teva Investigational Site 13315
Eagle, Idaho
Teva Investigational Site 12426
Edmond, Oklahoma
Teva Investigational Site 12440
El Paso, Texas
Teva Investigational Site 12454
Encinitas, California
Teva Investigational Site 12432
Fall River, Massachusetts
Teva Investigational Site 12456
Fresno, California
Teva Investigational Site 12461
Fullerton, California
Teva Investigational Site 12448
Greenfield, Wisconsin
Teva Investigational Site 12431
Greenville, South Carolina
Teva Investigational Site 12410
Huntington Beach, California
Teva Investigational Site 12452
Huntington Beach, California
Teva Investigational Site 12447
Killeen, Texas
Teva Investigational Site 13003
Knoxville, Tennessee
Teva Investigational Site 13004
Largo, Florida
Teva Investigational Site 13021
Las Vegas, Nevada
Teva Investigational Site 12599
Little Rock, Alaska
Teva Investigational Site 12417
Long Beach, California
Teva Investigational Site 12406
Medford, Oregon
Teva Investigational Site 12414
Miami, Florida
Teva Investigational Site 12437
Miami, Florida
Teva Investigational Site 12460
Middleburg Heights, Ohio
Teva Investigational Site 13020
Minneapolis, Minnesota
Teva Investigational Site 13017
Mission Viejo, California
Teva Investigational Site 12610
Missoula, Montana
Teva Investigational Site 12465
Mt. Pleasant, South Carolina
Teva Investigational Site 12467
Mt. Pleasant, South Carolina
Teva Investigational Site 12563
Normal Square, Pennsylvania
Teva Investigational Site 12441
North Dartmouth, Massachusetts
Teva Investigational Site 12466
North Dartmouth, Massachusetts
Teva Investigational Site 13008
Oklahoma City, Oklahoma
Teva Investigational Site 12420
Orangeburg, South Carolina
Teva Investigational Site 12427
Orlando, Florida
Teva Investigational Site 12423
Ormond Beach, Florida
Teva Investigational Site 12604
Panama City, Florida
Teva Investigational Site 12609
Phoenix, Arizona
Teva Investigational Site 12443
Pittsburgh, Pennsylvania
Teva Investigational Site 12442
Portland, Oregon
Teva Investigational Site 12407
Raleigh, North Carolina
Teva Investigational Site 12462
Rancho Mirage, California
Teva Investigational Site 12605
Richmond, Virginia
Teva Investigational Site 12439
River Forest, Illinois
Teva Investigational Site 12433
Rock Hill, South Carolina
Teva Investigational Site 12421
Rolla, Missouri
Teva Investigational Site 12411
Rolling Hills Estates, California
Teva Investigational Site 13001
Royal Oak, Michigan
Teva Investigational Site 13318
San Antonio, Texas
Teva Investigational Site 13018
San Diego, California
Teva Investigational Site 12413
San Jose, California
Teva Investigational Site 12435
Savannah, Georgia
Teva Investigational Site 12449
Shiloh, Illinois
Teva Investigational Site 12409
Skillman, New Jersey
Teva Investigational Site 12457
South Bend, Indiana
Teva Investigational Site 12422
South Burlington, Vermont
Teva Investigational Site 12436
Spokane, Washington
Teva Investigational Site 12412
St Louis, Missouri
Teva Investigational Site 12453
St Louis, Missouri
Teva Investigational Site 12403
Stockton, California
Teva Investigational Site 13002
Sugar Land, Texas
Teva Investigational Site 12564
Tacoma, Washington
Teva Investigational Site 13316
Tamarac, Florida
Teva Investigational Site 12603
The Bronx, New York
Teva Investigational Site 12444
Upland, California
Teva Investigational Site 12438
Upland, Pennsylvania
Teva Investigational Site 12999
Vista, California
Teva Investigational Site 12424
Waco, Texas
Teva Investigational Site 12459
Waterbury, Connecticut
Teva Investigational Site 12606
Winter Park, Florida
Teva Investigational Site 12428
Ypsilanti, Michigan
Poland23 sites
Teva Investigational Site 53199
Bialystok
Teva Investigational Site 53200
Bialystok
Teva Investigational Site 53202
Bialystok
Teva Investigational Site 53208
Bialystok
Teva Investigational Site 53210
Bydgoszcz
Teva Investigational Site 53227
Bydgoszcz
Teva Investigational Site 53225
Dębica
Teva Investigational Site 53203
Gdansk
Teva Investigational Site 53195
Krakow
Teva Investigational Site 53197
Krakow
Teva Investigational Site 53205
Krakow
Teva Investigational Site 53228
Lodz
Teva Investigational Site 53240
Lodz
Teva Investigational Site 53201
Lódz
Teva Investigational Site 53229
Lódz
Teva Investigational Site 53241
Lublin
Teva Investigational Site 53206
Poznan
Teva Investigational Site 53211
Poznan
Teva Investigational Site 53230
Strzelce Opolskie
Teva Investigational Site 53196
Tarnów
Teva Investigational Site 53222
Warsaw
Teva Investigational Site 53198
Wroclaw
Teva Investigational Site 53224
Wroclaw
Hungary18 sites
Teva Investigational Site 51149
Budapest
Teva Investigational Site 51155
Budapest
Teva Investigational Site 51157
Budapest
Teva Investigational Site 51161
Budapest
Teva Investigational Site 51154
Debrecen
Teva Investigational Site 51152
Deszk
Teva Investigational Site 51170
Dombóvár
Teva Investigational Site 51158
Kiskunhalas
Teva Investigational Site 51153
Miskolc
Teva Investigational Site 51156
Mosdós
Teva Investigational Site 51150
Nyíregyháza
Teva Investigational Site 51151
Nyíregyháza
Teva Investigational Site 51148
Százhalombatta
Teva Investigational Site 51146
Szeged
Teva Investigational Site 51162
Szigetvár
Teva Investigational Site 51147
Szombathely
Teva Investigational Site 51176
Tatabánya
Teva Investigational Site 51177
Törökbálint
Russia12 sites
Teva Investigational Site 50255
Chelyabinsk
Teva Investigational Site 50241
Kazan'
Teva Investigational Site 50250
Moscow
Teva Investigational Site 50252
Moscow
Teva Investigational Site 50242
Saint Petersburg
Teva Investigational Site 50245
Saint Petersburg
Teva Investigational Site 50246
Saint Petersburg
Teva Investigational Site 50254
Saratov
Teva Investigational Site 50244
Tomsk
Teva Investigational Site 50251
Voronezh
Teva Investigational Site 50275
Yaroslavl
Teva Investigational Site 50243
Yekaterinburg
South Africa6 sites
Teva Investigational Site 90011
Berea
Teva Investigational Site 90015
Bloemfontein
Teva Investigational Site 90012
Cape Town
Teva Investigational Site 90013
Centurion
Teva Investigational Site 90016
Middelburg
Teva Investigational Site 90014
Pretoria
Czechia4 sites
Teva Investigational Site 54096
Jindřichův Hradec
Teva Investigational Site 54098
Prague
Teva Investigational Site 54095
Rokycany
Teva Investigational Site 54094
Strakonice
Ukraine3 sites
Teva Investigational Site 58133
Kharkiv
Teva Investigational Site 58135
Kharkiv
Teva Investigational Site 58132
Kyiv
Canada2 sites
Teva Investigational Site 11072
Toronto, Ontario
Teva Investigational Site 11075
Vancouver, Quebec
About this study
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
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- FS MDPI, Fp MDPI, Placebo MDPI, Albuterol/salmeterol HFA MDI
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FS MDPIDrug
Also called fluticasone propionate, inhaled corticosteroid, salmeterol xinafoate, β2 adrenoceptor agonist
FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate 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 fluticasone propionate/salmeterol MDPI 200/12.5 mcg or fluticasone propionate/salmeterol MDPI 100/12.5 mcg twice a day for a total daily dose of 200/25 mcg or 400/25 mcg.
Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.
Fp MDPIDrug
Also called fluticasone propionate, inhaled corticosteroid
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 either 200 mcg or 100 mcg of Fp one inhalation twice a day for a total daily dose of 400 mcg or 200 mcg.
Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.
Placebo MDPIDrug
Also called inert powder
The placebo multidose dry powder inhaler (MDPI) 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). Patients were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.
Albuterol/salmeterol HFA MDIDrug
Also called short-acting β2-adrenergic agonists
Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
| Study group | Role | What they receive |
|---|---|---|
| FS MDPI 200 / 12.5 mcg | Experimental | Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. Receives: Drug: FS MDPI; Drug: Albuterol/salmeterol HFA MDI |
| FS MDPI 100 / 12.5 mcg | Experimental | Participants 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. Receives: Drug: FS MDPI; Drug: Albuterol/salmeterol HFA MDI |
| Fp MDPI 200 mcg | Experimental | Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks. Receives: Drug: Fp MDPI; Drug: Albuterol/salmeterol HFA MDI |
| Fp MDPI 100 mcg | Experimental | Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks. Receives: Drug: Fp MDPI; Drug: Albuterol/salmeterol HFA MDI |
| Placebo MDPI | Placebo comparator | Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks. Receives: Drug: Placebo MDPI; Drug: Albuterol/salmeterol HFA MDI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
A subset of patients performed postdose serial spirometry. 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.
Measured: 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 is a morning spirometry taken predose and pre-rescue bronchodilator. 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).
Measured: Day 1 (predose, baseline), Week 12
Secondary outcomes (7)
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.
Measured: Days -6 to Day 1 (predose, baseline), 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.
Daytime Symptom Score:
- 0=No symptoms
- 1=Symptoms for 1 short period
- 2=Symptoms for 2+ short periods
- 3=Symptoms for most of the day - did not affect normal daily activities
- 4=Symptoms for most of the day - did affect normal daily activities
- 5=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
- 1=Symptoms causing me to wake once (or wake early)
- 2=Symptoms causing me to wake twice or more (including waking early)
- 3=Symptoms causing me to be awake for most of the night
- 4=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).
Measured: 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.
Measured: 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.
Measured: 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 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.
Measured: 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
The baseline forced expiratory volume in 1 second (FEV1) was the average of the 2 predose 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, the baseline trough FEV1 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 NA indicate the values could not be estimated which happened when the estimated probability of not achieving target is more than 50%.
Measured: 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. Relation 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.
Measured: Day 1 to Week 12 of the Treatment Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startJun 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 882 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Teva Medical Expert, MD, Study director, Teva Branded Pharmaceutical Products R&D, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02141854
- Sponsor's protocol ID
- FSS-AS-30017
- Other IDs
- 2014-000923-25, 2014
- Status last verified
- Nov 2021
- First submitted
- 9 May 2014
- Last updated
- 9 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28639542Miller 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.
PubMed 27216137
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02141854
- Acronym / sponsor ID
- FSS-AS-30017
- Conditions
- Asthma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 882 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 20 May 2014 (estimated)
- Results
- Posted 12 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| FS MDPI 200 / 12.5 mcg | Experimental | Drug: FS MDPI, Drug: Albuterol/salmeterol HFA MDIParticipants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. |
| FS MDPI 100 / 12.5 mcg | Experimental | Drug: FS MDPI, Drug: Albuterol/salmeterol HFA MDIParticipants 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. |
| Fp MDPI 200 mcg | Experimental | Drug: Fp MDPI, Drug: Albuterol/salmeterol HFA MDIParticipants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks. |
| Fp MDPI 100 mcg | Experimental | Drug: Fp MDPI, Drug: Albuterol/salmeterol HFA MDIParticipants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks. |
| Placebo MDPI | Placebo comparator | Drug: Placebo MDPI, Drug: Albuterol/salmeterol HFA MDIParticipants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of their predicted normal value.
- 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.
- 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.
- 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.
- 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.
Key exclusion criteria (20 listed)
- 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).
- The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the study.
- The patient has participated as a randomized patient in any investigational drug study within 30 days of the SV.
- The patient has previously participated as a randomized patient in a study of Fp MDPI or FS MDPI.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FS MDPIAlso: fluticasone propionate, inhaled corticosteroid, salmeterol xinafoate, β2 adrenoceptor agonistFS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate 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 fluticasone propionate/salmeterol MDPI 200/12.5 mcg or fluticasone propionate/salmeterol MDPI 100/12.5 mcg twice a day for a total daily dose of 200/25 mcg or 400/25 mcg. Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration. | Drug | FS MDPI 100 / 12.5 mcg, FS MDPI 200 / 12.5 mcg |
| Fp MDPIAlso: fluticasone propionate, inhaled corticosteroidFp 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 either 200 mcg or 100 mcg of Fp one inhalation twice a day for a total daily dose of 400 mcg or 200 mcg. Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration. | Drug | Fp MDPI 100 mcg, Fp MDPI 200 mcg |
| Placebo MDPIAlso: inert powderThe placebo multidose dry powder inhaler (MDPI) 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). Patients were instructed to rinse their mouth and expectorate (not swallow) after study drug administration. | Drug | Placebo MDPI |
| Albuterol/salmeterol HFA MDIAlso: short-acting β2-adrenergic agonistsAlbuterol/salmeterol 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 100 / 12.5 mcg, FS MDPI 200 / 12.5 mcg, Fp MDPI 100 mcg, Fp MDPI 200 mcg, Placebo MDPI |
Primary outcome
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
Time frame: 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
A subset of patients performed postdose serial spirometry. 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.
Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
Time frame: Day 1 (predose, baseline), Week 12
Trough FEV1 is a morning spirometry taken predose and pre-rescue bronchodilator. 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).
7 secondary outcomes
Change From Baseline in the Weekly Average of the Daily Morning Trough Peak Expiratory Flow (PEF) Over the 12 Week Treatment
Time frame: Days -6 to Day 1 (predose, baseline), 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
Time frame: 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
Time frame: Days -6 to Day 1 (predose, baseline), up to week 12
Kaplan-Meier Estimate of Probability of Remaining in Study At Week 12
Time frame: 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
Time frame: 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
Time frame: Day 1 of the Treatment Period (predose and postdose)
Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
Time frame: Day 1 to Week 12 of the Treatment Period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28639542Sher 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.
- Derived from this study: PubMed 27216137Miller 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.
Related trials for Asthma
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teva Medical Expert, MD study director
Teva Branded Pharmaceutical Products R&D, Inc.
154 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FS MDPI, Fp MDPI and Albuterol/salmeterol HFA MDI in people with Asthma, run by Teva Branded Pharmaceutical Products R&D, Inc. at 154 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 154 sites in United States, Poland, Hungary, Russia, South Africa and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02141854, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2021.