Clinical trial NCT03015259: Randomized, Placebo-controlled, Multi-dose, Study Comparing Budesonide/Formoterol to Symbicort® in Asthmatic Patients
Official title: Randomized, Single Blind, Parallel Group, Placebo Controlled, Multidose Study Comparing the Therapeutic Equivalence of a 3M Budesonide/Formoterol Fumarate Inhaler and a Symbicort® Reference Inhaler in Adult Subjects With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: bioequivalence
Lead sponsor: Kindeva Drug Delivery
Sponsor class: INDUSTRY
First posted: 2017-01-10
Enrollment: 1762
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized multiple-dose, placebo-controlled, parallel group design consisting of a 2-week run-in period followed by a 6-week treatment period of the placebo, Test product (Budesonide 80 mcg / Formoterol fumarate dihydrate 4.5 mcg), or Reference product Symbicort® inhalation aerosol.

Detailed description: This is a pivotal trial that will examine therapeutic equivalence of a new generic fixed-dose combination product containing Budesonide 80 mcg / Formoterol fumarate dihydrate 4.5 mcg and reference listed drug (RLD) Symbicort® inhalation aerosol in adult patients with chronic but stable asthma as defined in National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP 3) guidelines. To ensure adequate study sensitivity the test and reference products should both be statistically superior to placebo (p\<0.05) with regard to the bioequivalent study primary endpoints.

A secondary study objective is the safety and tolerability of the test compound.

Eligibility criteria: Inclusion Criteria:

* Adult male or female subjects of non-childbearing or of childbearing potential committed to consistent and correct use of an acceptable method of birth control
* Diagnosed with asthma, as defined by the National Asthma Education and Prevention Program (NAEPP),at least 6 months prior to screening
* Moderate-to-severe asthma with a pre-bronchodilator FEV1 of \>45% and \<85% of predicted normal, measured at least 6 hours after short-acting β agonist (SABA)and at least 24 hours after the last dose of long-acting β agonist (LABA), at the screening visit and on the day of treatment
* \>15% and \>0.20 L reversibility of FEV1 within 30 minutes following 360 mcg of albuterol inhalation (pMDI)
* Patients should be stable on their chronic asthma treatment regimen for at least 4 weeks prior to enrollment
* Currently non-smoking; having not used tobacco products (i.e., cigarettes, cigars, pipe tobacco) within the past year, and having \< 10 pack-years of historical use
* Able to replace current regularly scheduled short-acting β agonists (SABAs) with salbutamol/albuterol inhaler for use only on an as-needed basis for the duration of the study (subjects should be able to withhold all inhaled SABAs for at least 6 hours prior to lung function assessments on study visits)
* Willing to discontinue their asthma medications (inhaled corticosteroids and long-acting β agonists) during the run-in period and for the remainder of the study
* Willingness to give their written informed consent to participate in the study

Exclusion Criteria:

* Life-threatening asthma, defined as a history of asthma episodes(s) requiring intubation, and/or associated with hypercapnia, respiratory arrest or hypoxic seizures, asthma-related syncopal episodes(s), or hospitalizations within the past year or during the run-in period
* Significant respiratory disease other than asthma (chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc.)
* Evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia. In addition, historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that, in the opinion of the investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbated during the study
* Patients who required systemic corticosteroids (for any reason) within the past 4 weeks
* Hypersensitivity to any sympathomimetic drug (e.g., formoterol or albuterol) or any inhaled, intranasal, or systemic corticosteroid therapy
* Patients currently receiving β-blockers

Primary outcomes:
measure: Area Under the Serial Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Day 1
measure: Change From Baseline in FEV1 Measured in the Morning at the End of Treatment Visit
timeFrame: Day 1 - Day 49
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 6 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama LLC
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortuim Arizona
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Allergy and Asthma Clinical Research Center
state: Arkansas
city: Anaheim
country: United States
facility: Anaheim Clinical Trials LLC
state: California
city: Encinitas
country: United States
facility: Warren W Pleskow MD
state: California
city: Huntington Beach
country: United States
facility: Allergy and Asthma Specialists Medical Group
state: California
city: Los Angeles
country: United States
facility: California Allergy and Asthma Medical Group Inc
state: California
city: Los Angeles
country: United States
facility: Jonathan Corren MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Southern California Institute For Respiratory Diseases, Inc.
state: California
city: Mission Viejo
country: United States
facility: Allergy and Asthma Associates of Southern California, A Medical Group, Inc.
state: California
city: Riverside
country: United States
facility: Integrated Research Group Inc
state: California
city: Sacramento
country: United States
facility: Allied Clinical Research LLC
state: California
city: San Jose
country: United States
facility: Allergy and Asthma Associates of Northern California
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Westminster
country: United States
facility: Allainz Research Institute Inc
state: California
city: Arvada
country: United States
facility: Western States Clinical Research Inc
state: Colorado
city: Centennial
country: United States
facility: Colorado Allergy and Asthma Centers PC
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates PC
state: Colorado
city: Denver
country: United States
facility: Colorado Allergy and Asthma Centers PC
state: Colorado
city: Lafayette
country: United States
facility: Innovative Clinical Research Inc
state: Colorado
city: Wheat Ridge
country: United States
facility: Rocky Mountain Center for Clinical Research
state: Colorado
city: Clearwater
country: United States
facility: Saint Francis Sleep Allergy and Lung Institute
state: Florida
city: Gainesville
country: United States
facility: Southeastern Integrated Medical
state: Florida
city: Largo
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic Inc
state: Florida
city: Miami
country: United States
facility: Prestige Clinical Research Center Inc
state: Florida
city: Miami
country: United States
facility: Clintex Research Group, Inc
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group LLC
state: Florida
city: Miami
country: United States
facility: Applemed Research Inc
state: Florida
city: Miami
country: United States
facility: Biotech Pharmaceutical Group, LLC
state: Florida
city: Miami
country: United States
facility: Research Institute of South Florida Inc
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute Inc
state: Florida
city: Panama City
country: United States
facility: Emerald Coast Research Associates
state: Florida
city: Tallahassee
country: United States
facility: Allergy and Asthma Dtc
state: Florida
city: River Forest
country: United States
facility: Asthma and Allergy Center of Chicago Sc
state: Illinois
city: Lenexa
country: United States
facility: Analab Clinical Research Inc
state: Kansas
city: Bangor
country: United States
facility: Paul Shapero's Private Practice
state: Maine
city: Baltimore
country: United States
facility: Chesapeake Clinical Research Inc
state: Maryland
city: Bethesda
country: United States
facility: Bethesda Allergy Asthma and Research Center LLC
state: Maryland
city: Fall River
country: United States
facility: Genesis Clinical Research and Consulting LLC
state: Massachusetts
city: North Dartmouth
country: United States
facility: Infinity Medical Research LLC
state: Massachusetts
city: North Dartmouth
country: United States
facility: Northeast Medical Research Associates Inc
state: Massachusetts
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc.
state: Minnesota
city: Columbia
country: United States
facility: Clinical Research of the Ozarks INC
state: Missouri
city: Rolla
country: United States
facility: Clinical Research of the Ozarks Inc
state: Missouri
city: Saint Louis
country: United States
facility: Midwest Clinical Research LLC
state: Missouri
city: Saint Louis
country: United States
facility: The Clinical Research Center LLC
state: Missouri
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: Bellevue
country: United States
facility: Pioneer Clinical Research LLC
state: Nebraska
city: Bellevue
country: United States
facility: The Asthma and Allergy Center PC
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Consortium Nevada
state: Nevada
city: Reno
country: United States
facility: Allied Clinical Research LLC
state: Nevada
city: Brick
country: United States
facility: Ocean Allergy & Respiratory Research Center
state: New Jersey
city: Ocean Township
country: United States
facility: Atlantic Research Center LLC
state: New Jersey
city: Skillman
country: United States
facility: Princeton Center For Clinical Research
state: New Jersey
city: Asheville
country: United States
facility: Allergy Partners of Western North Carolina
state: North Carolina
city: Fayetteville
country: United States
facility: Rapha Institute for Clinical Research
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Canton
country: United States
facility: Empirical Medical Research
state: Ohio
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center Inc
state: Ohio
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Sylvania
country: United States
facility: Toledo Center For Clinical Research
state: Ohio
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research
state: Ohio
city: Edmond
country: United States
facility: OK Clinical Research, LLC
state: Oklahoma
city: Edmond
country: United States
facility: Oklahoma Institute of Allergy and Asthma Clinical Research LLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: Santiago Reyes, MD
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute PC
state: Oklahoma
city: Eugene
country: United States
facility: Allergy and Asthma Research Group
state: Oregon
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon PC
state: Oregon
city: Portland
country: United States
facility: Allergy Associates Research Center LLC
state: Oregon
city: Jenkintown
country: United States
facility: Clinical Trial Center LLC
state: Pennsylvania
city: Smithfield
country: United States
facility: Montgomery Medical Inc
state: Pennsylvania
city: Warwick
country: United States
facility: Asthma & Allergy Physicians of Rhode Island Clinical Research Institute
state: Rhode Island
city: Greenville
country: United States
facility: ADAC Research
state: South Carolina
city: North Charleston
country: United States
facility: National Allergy and Asthma Research, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: S. Carolina Pharmaceutical Research
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting Inc
state: Texas
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonology & Sleep Center
state: Texas
city: New Braunfels
country: United States
facility: Central Texas Health Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Quality Assurance Research Center
state: Texas
city: San Antonio
country: United States
facility: Allergy and Asthma Research Center PA
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
city: Waco
country: United States
facility: Allergy Asthma Research Institute
state: Texas
city: Provo
country: United States
facility: National Clinical Resources Inc
state: Utah
city: South Burlington
country: United States
facility: Timber Lane Allergy and Asthma Research LLC
state: Vermont
city: Henrico
country: United States
facility: Clinical Research Partners LLC
state: Virginia
city: Spokane
country: United States
facility: Marycliff Allergy Specialists PS
state: Washington
city: Greenfield
country: United States
facility: Allergy Asthma and Sinus Center
state: Wisconsin
Study officials:
affiliation: Kindeva Drug Delivery
name: KINDEVA I DD, PhD
role: STUDY_CHAIR
References: