MGR001 / Advair Diskus Local Equivalence Study in Asthma

A Randomized, Double-blind, Double Dummy, Parallel Group Study to Determine the Local Equivalence of Multiple Doses of MGR001 to Advair Diskus Administered Via Oral Inhalation in Adult Asthma Patients

The purpose of this study is to determine whether MGR001 is equivalent to Advair Diskus when administered by inhalation in adult asthma patients

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate); Drug: Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1128
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Mylan Investigative Site #1
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Mylan Investigative Site #2
  • California
    • Anaheim, California, United States, 92801
      • Mylan Investigative Site #3
    • Bakersfield, California, United States, 93301
      • Mylan Investigative Site #4
    • Burbank, California, United States, 91505
      • Mylan Investigative Site #5
    • Costa Mesa, California, United States, 92626
      • Mylan Investigative Site #6
    • Encinitas, California, United States, 92024
      • Mylan Investigative Site #7
    • Fresno, California, United States, 93720
      • Mylan Investigative Site #8
    • Fullerton, California, United States, 92835
      • Mylan Investigative Site #9
    • Huntington Beach, California, United States, 92647
      • Mylan Investigative Site #10
    • Huntington Beach, California, United States, 92647
      • Mylan Investigative Site #11
    • Los Angeles, California, United States, 90025
      • Mylan Investigative Site #12
    • Los Angeles, California, United States, 90025
      • Mylan Investigative Site #13
    • Los Angeles, California, United States, 90048
      • Mylan Investigative Site #14
    • Mission Viejo, California, United States, 92691
      • Mylan Investigative Site #15
    • Napa, California, United States, 94558
      • Mylan Investigative Site #16
    • Orange, California, United States, 92868
      • Mylan Investigative Site #17
    • Riverside, California, United States, 92506
      • Mylan Investigative Site #18
    • Rolling Hills Estates, California, United States, 90274
      • Mylan Investigational Site #27
    • Sacramento, California, United States, 95842
      • Mylan Investigative Site #19
    • San Diego, California, United States, 92123
      • Mylan Investigative Site #20
    • San Jose, California, United States, 95117
      • Mylan Investigative Site #21
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Mylan Investigative Site #101
    • Centennial, Colorado, United States, 80112
      • Mylan Investigative Site #22
    • Colorado Springs, Colorado, United States, 80907
      • Mylan Investigative Site #23
    • Colorado Springs, Colorado, United States, 80907
      • Mylan Investigative Site #24
    • Denver, Colorado, United States, 80230
      • Mylan Investigative Site #25
    • Wheat Ridge, Colorado, United States, 80033
      • Mylan Investigative Site #26
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Mylan Investigative Site #28
    • Gainesville, Florida, United States, 32607
      • Mylan Investigative Site #29
    • Hialeah, Florida, United States, 33012
      • Mylan Investigative Site #30
    • Largo, Florida, United States, 33770
      • Mylan Investigative Site #31
    • Miami, Florida, United States, 33015
      • Mylan Investigative Site #32
    • Miami, Florida, United States, 33133
      • Mylan Investigative Site #34
    • Miami, Florida, United States, 33134
      • Mylan Investigative Site #33
    • Miami, Florida, United States, 33155
      • Mylan Investigative Site #35
    • New Port Richey, Florida, United States, 34653
      • Mylan Investigative Site #36
    • Tallahassee, Florida, United States, 32308
      • Mylan Investigative Site #37
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Mylan Investigative Site #38
  • Illinois
    • River Forest, Illinois, United States, 60305
      • Mylan Investigative Site #39
    • Shiloh, Illinois, United States, 62269
      • Mylan Investigative Site #40
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Mylan Investigative Site #41
  • Maine
    • Bangor, Maine, United States, 04401
      • Mylan Investigative Site #42
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Mylan Investigative Site #43
    • Bethesda, Maryland, United States, 20814
      • Mylan Investigative Site #44
    • Wheaton, Maryland, United States, 20902
      • Mylan Investigative Site #45
    • White Marsh, Maryland, United States, 21162
      • Mylan Investigative Site #46
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Mylan Investigative Site #47
    • North Dartmouth, Massachusetts, United States, 02747
      • Mylan Investigative Site #48
    • North Dartmouth, Massachusetts, United States, 02747
      • Mylan Investigative Site #49
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Mylan Investigative Site #50
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Mylan Investigative Site #51
    • Rolla, Missouri, United States, 65401
      • Mylan Investigative Site #52
    • Saint Louis, Missouri, United States, 63141
      • Mylan Investigative Site #53
    • Warrensburg, Missouri, United States, 64093
      • Mylan Investigative Site #54
  • Montana
    • Bozeman, Montana, United States, 59718
      • Mylan Investigative Site #55
    • Missoula, Montana, United States, 59808
      • Mylan Investigative Site #56
  • Nebraska
    • Bellevue, Nebraska, United States, 68123-4303
      • Mylan Investigative Site #57
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Mylan Investigative Site #58
    • Ocean City, New Jersey, United States, 07712
      • Mylan Investigative Site #59
    • Skillman, New Jersey, United States, 08558
      • Mylan Investigative Site #60
  • New York
    • New York, New York, United States, 11570
      • Mylan Investigative Site #61
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mylan Investigative Site #62
    • Charlotte, North Carolina, United States, 28207
      • Mylan Investigative Site #63
    • Raleigh, North Carolina, United States, 27607
      • Mylan Investigative Site #64
  • Ohio
    • Canton, Ohio, United States, 44718
      • Mylan Investigative Site #65
    • Cincinnati, Ohio, United States, 45231
      • Mylan Investigative Site #66
    • Cincinnati, Ohio, United States, 45242
      • Mylan Investigative Site #67
    • Sylvania, Ohio, United States, 43560
      • Mylan Investigative Site #68
    • Toledo, Ohio, United States, 43617
      • Mylan Investigative Site #69
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Mylan Investigative Site #70
    • Tulsa, Oklahoma, United States, 74136-8303
      • Mylan Investigative Site #71
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Mylan Investigative Site #72
    • Lake Oswego, Oregon, United States, 97035
      • Mylan Investigative Site #73
    • Medford, Oregon, United States, 97504
      • Mylan Investigative Site #74
    • Portland, Oregon, United States, 97202
      • Mylan Investigative Site #75
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Mylan Investigative Site #76
    • Pittsburgh, Pennsylvania, United States, 15243
      • Mylan Investigative Site #77
    • Smithfield, Pennsylvania, United States, 15478
      • Mylan Investigative Site #78
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Mylan Investigative Site #79
    • Warwick, Rhode Island, United States, 02886
      • Mylan Investigative Site #80
  • South Carolina
    • North Charleston, South Carolina, United States, 29420
      • Mylan Investigative Site #81
    • Spartanburg, South Carolina, United States, 29303
      • Mylan Investigative Site #82
    • Spartanburg, South Carolina, United States, 29303
      • Mylan Investigative Site #83
  • Texas
    • Boerne, Texas, United States, 78006
      • Mylan Investigative Site #84
    • Dallas, Texas, United States, 75231
      • Mylan Investigative Site #85
    • Dallas, Texas, United States, 75231
      • Mylan Investigative Site #86
    • Dickinson, Texas, United States, 77539
      • Mylan Investigative Site #87
    • El Paso, Texas, United States, 79903
      • Mylan Investigative Site #88
    • New Braunfels, Texas, United States, 78130
      • Mylan Investigative Site #89
    • San Antonio, Texas, United States, 78229
      • Mylan Investigative Site #90
    • San Antonio, Texas, United States, 78229
      • Mylan Investigative Site #91
    • Waco, Texas, United States, 76712
      • Mylan Investigative Site #92
  • Utah
    • Provo, Utah, United States, 84604
      • Mylan Investigative Site #93
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Mylan Investigative Site #94
  • Virginia
    • Henrico, Virginia, United States, 23233
      • Mylan Investigative Site #95
  • Washington
    • Seattle, Washington, United States, 98115
      • Mylan Investigative Site #96
    • Spokane, Washington, United States, 99204
      • Mylan Investigative Site #97
    • Tacoma, Washington, United States, 98405
      • Mylan Investigative Site #98
    • Tacoma, Washington, United States, 98405
      • Mylan Investigative Site #99
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Mylan Investigative Site #100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key inclusion criteria include:

• Male or female subjects aged ≥18 years. Females may be of either childbearing or non-childbearing potential
• Physician diagnosed history of asthma for at least 12 weeks prior to screening
• pre-bronchodilator FEV1 60-85% at screening and other specified visits
• Post-bronchodilator reversibility >/=12%
• Non-smokers and prior smokers with no history of smoking within the past 12 months prior to screening and a total smoking history of ≤10 pack-years
• Subjects able to discontinue asthma medications for the duration of the study and be maintained using albuterol as required
• Body mass index between 18-40 kg/m2 inclusive

Key exclusion criteria include:

• Presence or recent history of any other active, severe, progressive, and/or uncontrolled clinical disease, eg, poorly controlled Type 1 or 2 diabetes, seizure disorder or epilepsy, cerebrovascular accident, significant cardiac conduction abnormalities
• Respiratory conditions other than asthma and allergic rhinitis, including but not limited to: severe nasal polyposis or chronic rhinosinusitis, chronic obstructive pulmonary disease, bronchiectasis, Churg-Strauss Disease, lung resection, pulmonary fibrosis (primary or secondary), pulmonary hypertension, cystic fibrosis, sarcoidosis
• History of life-threatening asthma, defined as a history of asthma episode(s) requiring intubation, and/or associated with hypercapnia; respiratory arrest or hypoxic seizures, asthma related syncopal episode(s)
• In patient hospitalization (not including ER visits) for an asthma exacerbation within the past year or during the run in period
• An asthma exacerbation requiring change in asthma therapy or oral/IV corticosteroids in the 3 months prior to screening
• History of seasonally unstable asthma where the season will coincide with the subject's participation in the study
• Use of prescription or non-prescription drugs, including beta blockers, tricyclic antidepressants, oral decongestants, benzodiazepines, digitalis, phenothiazines, monoamine oxidase inhibitors, etc
• Suspected hypersensitivity to the study drugs (including lactose) or severe milk protein allergy
• Clinically significant abnormalities in the screening ECG
• Evidence of alcohol or drug abuse or dependency within 6 months prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MGR001; MGR001 administered two times per day by inhalation throughout the study	Drug: MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate); Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device
Active Comparator: Advair Diskus; Advair Diskus administered two times per day by inhalation throughout the study	Drug: Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate); Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device
Placebo Comparator: Placebo; Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study	Drug: Placebo; Placebo administered via the CRC749 and Diskus devices

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Exhaled Volume in 1 Sec (FEV1) Area Under the Effect Curve on Day 1 (Assay Sensitivity)	The FEV1 AUEC(0-12) on Day 1 was calculated from FEV1 measurements collected 30 minutes prior to morning dose, 0 minutes prior to morning dose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours following completion of dosing on Day 1 (Visit 3). The baseline for the FEV1 AUEC(0-12) endpoint was the mean of the 2 predose FEV1 measures. To confirm assay sensitivity, both active treatments (MGR001 and Advair Diskus) had to be significantly superior to placebo	0-12 hours after dosing on Day 1
Forced Exhaled Volume in 1 Sec (FEV1) Area Under the Effect Curve on Day 1 (Bioequivalence)	The FEV1 AUEC(0-12) on Day 1 was calculated from FEV1 measurements collected 30 minutes prior to morning dose, 0 minutes prior to morning dose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours following completion of dosing on Day 1 (Visit 3). The baseline for the FEV1 AUEC(0-12) endpoint was the mean of the 2 predose FEV1 measures	0-12 hours after dosing on Day 1
FEV1 Trough Value (Assay Sensitivity)	Change from baseline in trough (pre-dose) FEV1 at Day 29 was based on 2 pre-dose FEV1 assessments performed 30 minutes apart on Day 29. Baseline was calculated by taking the mean of [prebronchodilator FEV1 measured at a run-in visit and the mean of 2 predose FEV1 measures taken at Day 1]. To confirm assay sensitivity, both active treatments (MGR001 and Advair Diskus) had to be significantly superior to placebo.	Day 1 and Day 29
FEV1 Trough Value (Bioequivalence)	Change from baseline in trough (pre-dose) FEV1 at Day 29 was based on 2 pre-dose FEV1 assessments performed 30 minutes apart on Day 29. Baseline was calculated by taking the mean of [prebronchodilator FEV1 measured at a run-in visit and the mean of 2 predose FEV1 measures taken at Day 1]	Day 1 and Day 29

Collaborators and Investigators

• Sponsor: Mylan Pharma UK Ltd.
• Investigators: Study Director: Dik WH Ng, PhD, Mylan Pharma UK Ltd.

Publications and helpful links

General Publications

• Ng D, Kerwin EM, White MV, Miller SD, Haughie S, Ward JK, Allan R. Clinical Bioequivalence of Wixela Inhub and Advair Diskus in Adults With Asthma. J Aerosol Med Pulm Drug Deliv. 2020 Apr;33(2):99-107. doi: 10.1089/jamp.2019.1547. Epub 2019 Oct 31.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: September 15, 2014
• First Submitted That Met QC Criteria: September 17, 2014
• First Posted (Estimate): September 19, 2014

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Asthma; FEV1; fluticasone; salmeterol; Diskus; MGR001; CRC749; Advair
• 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; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Salmeterol Xinafoate
• Other Study ID Numbers: MGR001-3001