Randomized, Placebo-controlled, Multi-dose, Study Comparing Budesonide/Formoterol to Symbicort® in Asthmatic Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Budesonide/Formoterol fumarate dihydrate; Drug: Symbicort; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 1762
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama LLC
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Tempe, Arizona, United States, 85253
      • Clinical Research Consortuim Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Allergy and Asthma Clinical Research Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials Llc
    • Encinitas, California, United States, 98104
      • Warren W Pleskow MD
    • Huntington Beach, California, United States, 92647
      • Allergy and Asthma Specialists Medical Group
    • Los Angeles, California, United States, 90048
      • Southern California Institute For Respiratory Diseases, Inc.
    • Los Angeles, California, United States, 90025
      • Jonathan Corren MD, Inc.
    • Los Angeles, California, United States, 90025
      • California Allergy and Asthma Medical Group Inc
    • Mission Viejo, California, United States, 92691
      • Allergy and Asthma Associates of Southern California, A Medical Group, Inc.
    • Riverside, California, United States, 92506
      • Integrated Research Group Inc
    • Sacramento, California, United States, 95842
      • Allied Clinical Research LLC
    • San Jose, California, United States, 95117
      • Allergy and Asthma Associates of Northern California
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Clinical Research
    • Westminster, California, United States, 92683
      • Allainz Research Institute Inc
  • Colorado
    • Arvada, Colorado, United States, 80401
      • Western States Clinical Research Inc
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
    • Centennial, Colorado, United States, 80112
      • Colorado Allergy and Asthma Centers PC
    • Colorado Springs, Colorado, United States, 80907
      • Asthma and Allergy Associates PC
    • Denver, Colorado, United States, 80230
      • Colorado Allergy and Asthma Centers PC
    • Lafayette, Colorado, United States, 80026
      • Innovative Clinical Research Inc
    • Wheat Ridge, Colorado, United States, 80033
      • Rocky Mountain Center for Clinical Research
  • Florida
    • Clearwater, Florida, United States, 33765
      • Saint Francis Sleep Allergy and Lung Institute
    • Gainesville, Florida, United States, 32607
      • Southeastern Integrated Medical
    • Largo, Florida, United States, 33756
      • Innovative Research of West Florida
    • Miami, Florida, United States, 33155
      • Biotech Pharmaceutical Group, LLC
    • Miami, Florida, United States, 33135
      • Suncoast Research Group LLC
    • Miami, Florida, United States, 33155
      • AppleMed Research Inc
    • Miami, Florida, United States, 33133
      • Prestige Clinical Research Center Inc
    • Miami, Florida, United States, 33173
      • Research Institute of South Florida Inc
    • Miami, Florida, United States, 33015
      • San Marcus Research Clinic Inc
    • Miami, Florida, United States, 33135
      • Clintex Research Group, Inc
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute Inc
    • Panama City, Florida, United States, 32405
      • Emerald Coast Research Associates
    • Tallahassee, Florida, United States, 32308
      • Allergy and Asthma DTC
  • Illinois
    • River Forest, Illinois, United States, 60305
      • Asthma and Allergy Center of Chicago SC
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Analab Clinical Research Inc
  • Maine
    • Bangor, Maine, United States, 04401
      • Paul Shapero's Private Practice
  • Maryland
    • Baltimore, Maryland, United States, 212236
      • Chesapeake Clinical Research Inc
    • Bethesda, Maryland, United States, 20814
      • Bethesda Allergy Asthma and Research Center LLC
  • Massachusetts
    • Fall River, Massachusetts, United States, 02723
      • Genesis Clinical Research and Consulting LLC
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research LLC
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates Inc
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Clinical Research of the Ozarks Inc
    • Rolla, Missouri, United States, 65401
      • Clinical Research of the Ozarks Inc
    • Saint Louis, Missouri, United States, 63141
      • The Clinical Research Center LLC
    • Saint Louis, Missouri, United States, 63141
      • Midwest Clinical Research LLC
  • Montana
    • Missoula, Montana, United States, 59808
      • Montana Medical Research
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Pioneer Clinical Research LLC
    • Bellevue, Nebraska, United States, 68123
      • The Asthma and Allergy Center PC
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Clinical Research Consortium Nevada
    • Reno, Nevada, United States, 89523
      • Allied Clinical Research LLC
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Ocean Allergy & Respiratory Research Center
    • Ocean Township, New Jersey, United States, 07712
      • Atlantic Research Center LLC
    • Skillman, New Jersey, United States, 08558
      • Princeton Center for Clinical Research
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Allergy Partners of Western North Carolina
    • Fayetteville, North Carolina, United States, 28314
      • Rapha Institute For Clinical Research
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • Empirical Medical Research
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center Inc
    • Sylvania, Ohio, United States, 43560
      • Toledo Center for Clinical Research
    • Toledo, Ohio, United States, 93617
      • Toledo Institute of Clinical Research
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • OK Clinical Research, LLC
    • Edmond, Oklahoma, United States, 73131
      • Oklahoma Institute of Allergy and Asthma Clinical Research LLC
    • Oklahoma City, Oklahoma, United States, 73112
      • Santiago Reyes, MD
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute PC
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Allergy and Asthma Research Group
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon PC
    • Portland, Oregon, United States, 97202
      • Allergy Associates Research Center LLC
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Clinical Trial Center LLC
    • Smithfield, Pennsylvania, United States, 15478
      • Montgomery Medical Inc
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Asthma & Allergy Physicians of Rhode Island Clinical Research Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • ADAC Research
    • North Charleston, South Carolina, United States, 29420
      • National Allergy and Asthma Research, LLC
    • Spartanburg, South Carolina, United States, 29303
      • S. Carolina Pharmaceutical Research
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
    • Dallas, Texas, United States, 75231
      • Pharmaceutical Research & Consulting Inc
    • El Paso, Texas, United States, 79903
      • Western Sky Medical Research
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonology & Sleep Center
    • New Braunfels, Texas, United States, 78130
      • Central Texas Health Research Corporation
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates
    • San Antonio, Texas, United States, 78207
      • Quality Assurance Research Center
    • San Antonio, Texas, United States, 78229
      • Allergy and Asthma Research Center PA
    • Waco, Texas, United States, 76712
      • Allergy Asthma Research Institute
  • Utah
    • Provo, Utah, United States, 84604
      • National Clinical Resources Inc
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Timber Lane Allergy and Asthma Research LLC
  • Virginia
    • Henrico, Virginia, United States, 23233
      • Clinical Research Partners Llc
  • Washington
    • Spokane, Washington, United States, 99202
      • Marycliff Allergy Specialists PS
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Allergy Asthma and Sinus Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1; Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period	Drug: Budesonide/Formoterol fumarate dihydrate; Experimental: Treatment 1; Other Names: Generic Budesonide/Formoterol fumarate dihydrate
Active Comparator: Treatment 2; Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period	Drug: Symbicort; Active Comparator: Treatment 2; Other Names: Budesonide/Formoterol fumarate dihydrate
Placebo Comparator: Treatment 3; Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period	Drug: Placebo; Placebo Comparator: Treatment 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Serial Forced Expiratory Volume in 1 Second (FEV1)	FEV1 Area calculated over 12 hours (measurements at 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose) on Day 1 of treatment. Because this was a primary endpoint, Per Protocol Population used to calculate this endpoint.	Day 1
Change From Baseline in FEV1 Measured in the Morning at the End of Treatment Visit	Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42 (+/- 7 days). Baseline was defined as the average of 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1].	Day 1 - Day 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of participants reporting at least one adverse event (safety population)	6 Weeks

Collaborators and Investigators

• Sponsor: Kindeva Drug Delivery
• Investigators: Study Chair: KINDEVA I DD, PhD, Kindeva Drug Delivery

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2016
• Primary Completion (Actual): February 8, 2018
• Study Completion (Actual): February 8, 2018

Study Registration Dates

• First Submitted: January 6, 2017
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimate): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): August 24, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: bioequivalence
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: CSP-07-000034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No