Clinical trial NCT02513160: Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 6-Week Clinical Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate Delivered Via Breath-Actuated Inhaler (BAI) at 320 or 640 mcg/Day in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Persistent Asthma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-31
Enrollment: 713
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 is to evaluate the efficacy of beclomethasone dipropionate administered via BAI at a dose strength of 40 or 80 mcg per oral inhalation (320 or 640 mcg/day, respectively) compared with placebo treatment in patients with persistent asthma as assessed by the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 6 weeks (AUEC\[0-6wk\]).

Detailed description: Run-In Period (Days -14 to Day -1): Participants were provided with single-blind placebo breath-actuated inhaler (BAI) or metered-dose inhaler (MDI) device for twice-daily use after appropriate training and demonstration of the proper technique. Participants discontinued their current asthma therapy for the duration of the study.

Treatment Period (Day 0 to Week 6): Participants were randomly assigned to treatment and device type through a qualified randomization service provider (ie, IRT). The interactive response technology (IRT) system stratified patients based on treatment at the time of screening visit, either inhaled corticosteroid (ICS) or non-corticosteroid (NCS). During the study, blinded persons were blinded to treatment (active or placebo) assigned but not device (BAI or MDI) assignment.

Eligibility criteria: Inclusion Criteria:

* The patient has a diagnosis of asthma as defined by the 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 medication) for at least 30 days.
* The patient has been maintained on stable doses of :

  * non-corticosteroid therapy
  * inhaled corticosteroid therapy
* Written informed consent/assent is obtained. For adult patients (18 years of age and older, or as applicable per local regulations), the written informed consent form (ICF) must be signed and dated by the patient before conducting any study-related procedure. 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 informed assent form must be signed and dated by the patient before conducting any study-related procedure.
* The patient is a male or female 12 years of age or older as of the visit when informed consent/assent is signed (screening or prescreening visit, as applicable). (Note: Age requirements are as specified or allowed by local regulations.)
* The patient is able to perform acceptable and repeatable spirometry
* The patient is able to use an electronic diary after training.
* The patient is able to use devices properly
* If female, patient is currently not pregnant, not breast feeding, nor attempting to become pregnant (for 30 days before the screening visit (SV) and throughout the duration of the study and for 30 days after patient's last study visit) or, is of childbearing potential and not sexually active, has a negative urine pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control
* If male, the patient is willing to commit to an acceptable method of birth control for the duration of the study, is surgically sterile or exclusively has same-sex partner(s).
* The patient does not have any concomitant conditions or treatments that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the study as judged by the investigator.
* The patient/parent/legal guardian 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 (eg, dose schedules, visit schedules, procedures, and record keeping).
* The patient, as judged by the investigator, is able to discontinue all asthma medications at the SV.

  * other criteria apply, please contact the investigator for more information

Exclusion Criteria

* Life-threatening asthma, defined as a history of asthma episode(s) requiring intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures, asthma-related syncopal episode(s), or hospitalizations within the past year.
* The patient received systemic corticosteroids within 30 days before the SV (for asthma exacerbation or for other indications).
* The patient has participated in any investigational drug study as a randomized patient within the 30 days (starting at the final visit of that study) preceding SV (or prescreening visit, as applicable), or plans to participate in another investigational drug study at any time during this study.
* The patient has previously participated in a beclomethasone dipropionate breath-actuated inhaler (device) (BAI) study as a randomized patient.
* The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation.
* The patient has been treated with any known strong cytochrome inhibitors during the study.
* The patient has been treated with any of the prohibited medications during the prescribed (per protocol) withdrawal 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 may not have used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco).
* The patient has a 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 SV.
* The patient has had an asthma exacerbation requiring oral corticosteroids within 1 month before the SV, or has had any hospitalization for asthma within 3 months before SV.
* The patient has initiated immunotherapy (administered by any route) less than 90 days before the SV or had a dose escalation of immunotherapy less than 30 days before the SV.
* The patient is unable to tolerate or unwilling to comply with the required washout periods and withholding of all applicable medications.
* The patient has untreated oral candidiasis at SV. Patients with clinical visual evidence of oral candidiasis and who agree to receive treatment and comply with appropriate medical monitoring may enter the study.
* 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 apply, please contact the investigator for more information

Primary outcomes:
measure: Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 6 Weeks (AUEC(0-6wk))
timeFrame: Baseline (Day 0 of Treatment Period), weeks 2, 4, 6
Secondary outcomes:
measure: Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Rate Over the 6-Week Treatment Period
timeFrame: Timeframes: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks
measure: Change From Baseline in Weekly Average of Daily Trough Morning Forced Expiratory Volume in One Minute (FEV1) Rate Over the 6-Week Treatment Period
timeFrame: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks
measure: Change From Baseline in Weekly Average of Total Daily (24-Hour) Rescue Medication Use Over the 6-Week Treatment Period
timeFrame: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks
measure: Change From Baseline in Weekly Average of Total Daily Asthma Symptom Score Over the 6-Week Treatment Period
timeFrame: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks
measure: Count of Participants Withdrawn From Study Drug Treatment Due to Meeting Stopping Criteria for Worsening Asthma
timeFrame: Day 0 to Week 6
measure: Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Day 0 to Week 6
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Teva Investigational Site 13415
state: Arizona
city: Downey
country: United States
facility: Teva Investigational Site 13389
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 13421
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 13434
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 13427
state: California
city: Mission Viejo
country: United States
facility: Teva Investigational Site 13386
state: California
city: Orange
country: United States
facility: Teva Investigational Site 13394
state: California
city: Riverside
country: United States
facility: Teva Investigational Site 13417
state: California
city: Rolling Hills Estates
country: United States
facility: Teva Investigational Site 13445
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 13420
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 13443
state: California
city: San Jose
country: United States
facility: Teva Investigational Site 13438
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 13397
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 13454
state: Colorado
city: Aventura
country: United States
facility: Teva Investigational Site 13404
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 13458
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 13416
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 13440
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 13455
state: Florida
city: Ormond Beach
country: United States
facility: Teva Investigational Site 13431
state: Florida
city: Sarasota
country: United States
facility: Teva Investigational Site 13437
state: Florida
city: Tallahassee
country: United States
facility: Teva Investigational Site 13425
state: Florida
city: Normal
country: United States
facility: Teva Investigational Site 13450
state: Illinois
city: River Forest
country: United States
facility: Teva Investigational Site 13448
state: Illinois
city: Lenexa
country: United States
facility: Teva Investigational Site 13408
state: Kansas
city: Baltimore
country: United States
facility: Teva Investigational Site 13410
state: Maryland
city: Bethesda
country: United States
facility: Teva Investigational Site 13422
state: Maryland
city: Wheaton
country: United States
facility: Teva Investigational Site 13435
state: Maryland
city: North Dartmouth
country: United States
facility: Teva Investigational Site 13411
state: Massachusetts
city: Plymouth
country: United States
facility: Teva Investigational Site 13398
state: Minnesota
city: Plymouth
country: United States
facility: Teva Investigational Site 13429
state: Minnesota
city: Columbia
country: United States
facility: Teva Investigational Site 13433
state: Missouri
city: Rolla
country: United States
facility: Teva Investigational Site 13432
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 13414
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 13430
state: Missouri
city: Bellevue
country: United States
facility: Teva Investigational Site 13384
state: Nebraska
city: Brick
country: United States
facility: Teva Investigational Site 13392
state: New Jersey
city: Ocean City
country: United States
facility: Teva Investigational Site 13426
state: New Jersey
city: Skillman
country: United States
facility: Teva Investigational Site 13419
state: New Jersey
city: Rochester
country: United States
facility: Teva Investigational Site 13388
state: New York
city: Hickory
country: United States
facility: Teva Investigational Site 13441
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 13403
state: North Carolina
city: Wilmington
country: United States
facility: Teva Investigational Site 13405
state: North Carolina
city: Canton
country: United States
facility: Teva Investigational Site 13395
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 13396
state: Ohio
city: Sylvania
country: United States
facility: Teva Investigational Site 13436
state: Ohio
city: Toledo
country: United States
facility: Teva Investigational Site 13423
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 13387
state: Oklahoma
city: Eugene
country: United States
facility: Teva Investigational Site 13453
state: Oregon
city: Lake Oswego
country: United States
facility: Teva Investigational Site 13439
state: Oregon
city: Medford
country: United States
facility: Teva Investigational Site 13402
state: Oregon
city: Portland
country: United States
facility: Teva Investigational Site 13412
state: Oregon
city: Pittsburgh
country: United States
facility: Teva Investigational Site 13391
state: Pennsylvania
city: East Providence
country: United States
facility: Teva Investigational Site 13449
state: Rhode Island
city: Warwick
country: United States
facility: Teva Investigational Site 13456
state: Rhode Island
city: North Charleston
country: United States
facility: Teva Investigational Site 13413
state: South Carolina
city: Knoxville
country: United States
facility: Teva Investigational Site 13390
state: Tennessee
city: Knoxville
country: United States
facility: Teva Investigational Site 13442
state: Tennessee
city: Austin
country: United States
facility: Teva Investigational Site 13400
state: Texas
city: Boerne
country: United States
facility: Teva Investigational Site 13452
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 13407
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 13424
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 13409
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 13451
state: Texas
city: New Braunfels
country: United States
facility: Teva Investigational Site 13399
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13393
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13444
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13446
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13457
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13459
state: Texas
city: Waco
country: United States
facility: Teva Investigational Site 13383
state: Texas
city: South Burlington
country: United States
facility: Teva Investigational Site 13401
state: Vermont
city: Richmond
country: United States
facility: Teva Investigational Site 13385
state: Virginia
city: Richmond
country: United States
facility: Teva Investigational Site 13447
state: Virginia
city: Greenfield
country: United States
facility: Teva Investigational Site 13428
state: Wisconsin
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Kerwin EM, Hickey L, Small CJ. Relationship between handheld and clinic-based spirometry measurements in asthma patients receiving beclomethasone. Respir Med. 2019 May;151:35-42. doi: 10.1016/j.rmed.2019.03.010. Epub 2019 Mar 20.
citation: Ostrom NK, Raphael G, Tillinghast J, Hickey L, Small CJ. Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma. Allergy Asthma Proc. 2018 Mar 9;39(2):117-126. doi: 10.2500/aap.2018.39.4115. Epub 2018 Jan 9.