Clinical Endpoint Bioequivalence Study for Fluticasone Propionate and Salmeterol Xinafoate

A Randomized, Parallel-Group, Placebo-Controlled, Clinical Endpoint Bioequivalence Study of Generic Fluticasone Propionate 100 µg and Salmeterol Xinafoate 50 µg Inhalation Powder Compared With Advair Diskus® 100/50 in Subjects With Asthma

A Randomized, Parallel-Group, Placebo-Controlled, Clinical Endpoint Bioequivalence Study of Generic Fluticasone Propionate 100 µg and Salmeterol Xinafoate 50 µg Inhalation Powder Compared with Advair Diskus® 100/50 in Subjects with Asthma

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: Fluticasone / Salmeterol; Drug: Advair Diskus 100/50

Detailed Description

The primary objective of this study is to evaluate the clinical bioequivalence of generic fluticasone propionate 100 µg and salmeterol xinafoate 50 µg inhalation powder (test) to Advair Diskus ("Advair") 100/50 (reference) for the treatment of asthma.

The secondary objectives of the study are:

• To demonstrate statistical superiority of generic fluticasone propionate 100 µg and salmeterol xinafoate 50 µg inhalation powder to placebo.
• To demonstrate statistical superiority of Advair 100/50 to placebo.
• To investigate the safety and tolerability of fluticasone propionate 100 µg and salmeterol xinafoate 50 µg inhalation powder compared with Advair 100/50 in the target population.

• Study Type: Interventional
• Enrollment (Actual): 1430
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Roxane Laboratories Research Site #30
    • Phoenix, Arizona, United States, 85018
      • Roxane Laboratories Research Site #46
    • Surprise, Arizona, United States, 85374
      • Roxane Laboratories Research Site #1
    • Tempe, Arizona, United States, 85283
      • Roxane Laboratories Research Site #13
  • California
    • Bakersfield, California, United States, 93301
      • Roxane Laboratories Research Site #84
    • Costa Mesa, California, United States, 92626
      • Roxane Laboratories Research Site #72
    • Encinitas, California, United States, 92024
      • Roxane Laboratories Research Site #67
    • Fountain Valley, California, United States, 90708
      • Roxane Laboratories Research Site #4
    • Fullerton, California, United States, 92835
      • Roxane Laboratories Research Site #64
    • Huntington Beach, California, United States, 92647
      • Roxane Laboratories Research Site #3
    • Huntington Beach, California, United States, 92647
      • Roxane Laboratories Research Site #70
    • Huntington Beach, California, United States, 92647
      • Roxane Laboratories Research Site #92
    • Irvine, California, United States, 92614
      • Roxane Laboratories Research Site #38
    • Lincoln, California, United States, 95648
      • Roxane Laboratories Research Site #91
    • Los Angeles, California, United States, 90017
      • Roxane Laboratories Research Site #59
    • Los Angeles, California, United States, 90025
      • Roxane Laboratories Research Site #16
    • Los Angeles, California, United States, 90048
      • Roxane Laboratories Research Site #90
    • Mission Viejo, California, United States, 92691
      • Roxane Laboratories Research Site #6
    • Rolling Hills Estates, California, United States, 90274
      • Roxane Laboratories Research Site #78
    • Sacramento, California, United States, 95821
      • Roxane Laboratories Research Site #98
    • San Diego, California, United States, 92103
      • Roxane Laboratories Research Site #53
    • San Diego, California, United States, 92123
      • Roxane Laboratories Research Site #93
    • San Jose, California, United States, 95117
      • Roxane Laboratories Research Site #28
    • Santa Monica, California, United States, 90404
      • Roxane Laboratories Research Site #60
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Roxane Laboratories Research Site #33
    • Denver, Colorado, United States, 80246
      • Roxane Laboratories Research Site #43
    • Denver, Colorado, United States, 80246
      • Roxane Laboratories Research Site #63
    • Wheat Ridge, Colorado, United States, 80033
      • Roxane Laboratories Research Site #21
  • Florida
    • Hialeah, Florida, United States, 33012
      • Roxane Laboratories Research Site #50
    • Hialeah, Florida, United States, 33016
      • Roxane Laboratories Research Site #11
    • Homestead, Florida, United States, 33030
      • Roxane Laboratories Research Site #66
    • Jupiter, Florida, United States, 33458
      • Roxane Laboratories Research Site #83
    • Miami, Florida, United States, 33126
      • Roxane Laboratories Research Site #8
    • Miami, Florida, United States, 33135
      • Roxane Laboratories Research Site #23
    • Miami, Florida, United States, 33144
      • Roxane Laboratories Research Site #86
    • Miami, Florida, United States, 33144
      • Roxane Laboratories Research Site #89
    • Miami, Florida, United States, 33155
      • Roxane Laboratories Research Site #20
    • Miami, Florida, United States, 33165
      • Roxane Laboratories Research Site #68
    • Miami, Florida, United States, 33173
      • Roxane Laboratories Research Site #80
    • Miami, Florida, United States, 33174
      • Roxane Laboratories Research Site #54
    • Miami, Florida, United States, 33185
      • Roxane Laboratories Research Site #12
    • North Miami Beach, Florida, United States, 33162
      • Roxane Laboratories Research Site #74
    • Orlando, Florida, United States, 32806
      • Roxane Laboratories Research Site #35
    • Orlando, Florida, United States, 32825
      • Roxane Laboratories Research Site #17
    • Port Orange, Florida, United States, 32127
      • Roxane Laboratories Research Site #94
  • Georgia
    • Lilburn, Georgia, United States, 30047
      • Roxane Laboratories Research Site #34
    • Rincon, Georgia, United States, 31326
      • Roxane Laboratories Research Site #51
  • Illinois
    • Normal, Illinois, United States, 61761
      • Roxane Laboratories Research Site #79
    • River Forest, Illinois, United States, 60305
      • Roxane Laboratories Research Site #47
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Roxane Laboratories Research Site #100
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Roxane Laboratories Research Site #62
    • Baltimore, Maryland, United States, 21236
      • Roxane Laboratories Research Site #52
    • Bethesda, Maryland, United States, 20814
      • Roxane Laboratories Research Site #71
    • Silver Spring, Maryland, United States, 20902
      • Roxane Laboratories Research Site #96
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Roxane Laboratories Research Site #81
    • North Dartmouth, Massachusetts, United States, 02747
      • Roxane Laboratories Research Site #56
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Roxane Laboratories Research Site #55
    • Chelsea, Michigan, United States, 48118
      • Roxane Laboratories Research Site #97
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Roxane Laboratories Research Site #5
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Roxane Laboratories Research Site #85
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Roxane Laboratories Research Site #32
    • Bellevue, Nebraska, United States, 68123
      • Roxane Laboratories Research Site #25
    • Omaha, Nebraska, United States, 68114
      • Roxane Laboratories Research Site #36
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Roxane Laboratories Research Site #57
  • New Jersey
    • Atco, New Jersey, United States, 08004
      • Roxane Laboratories Research Site #10
    • Skillman, New Jersey, United States, 08558
      • Roxane Laboratories Research Site #65
  • New York
    • New York, New York, United States, 10018
      • Roxane Laboratories Research Site #7
    • New York, New York, United States, 10019
      • Roxane Laboratories Research Site #2
  • North Carolina
    • Clemmons, North Carolina, United States, 27012
      • Roxane Laboratories Research Site #41
    • Raleigh, North Carolina, United States, 27607
      • Roxane Laboratories Research Site #45
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Roxane Laboratories Research Site #31
    • Columbus, Ohio, United States, 43214
      • Roxane Laboratories Research Site #95
    • Hilliard, Ohio, United States, 43026
      • Roxane Laboratories Research Site #24
    • Middleburg Heights, Ohio, United States, 44130
      • Roxane Laboratories Research Site #61
    • Toledo, Ohio, United States, 43617
      • Roxane Laboratories Research Site #73
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Roxane Laboratories Research Site #14
    • Oklahoma City, Oklahoma, United States, 73103
      • Roxane Laboratories Research Site #15
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Roxane Laboratories Research Site #37
    • Medford, Oregon, United States, 97504
      • Roxane Laboratories Research Site #40
    • Portland, Oregon, United States, 97202
      • Roxane Laboratories Research Site #58
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Roxane Laboratories Research Site #26
    • Warwick, Rhode Island, United States, 02886
      • Roxane Laboratories Research Site #99
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Roxane Laboratories Research Site #69
    • Spartanburg, South Carolina, United States, 29303
      • Roxane Laboratories Research Site #22
  • Tennessee
    • Smyrna, Tennessee, United States, 37167
      • Roxane Laboratories Research Site #19
  • Texas
    • Boerne, Texas, United States, 78006
      • Roxane Laboratories Research Site #27
    • Dallas, Texas, United States, 75231
      • Roxane Laboratories Research Site #75
    • El Paso, Texas, United States, 79903
      • Roxane Laboratories Research Site #49
    • Houston, Texas, United States, 77043
      • Roxane Laboratories Research Site #44
    • Lewisville, Texas, United States, 75067
      • Roxane Laboratories Research Site #77
    • Plano, Texas, United States, 75093
      • Roxane Laboratories Research Site #87
    • San Antonio, Texas, United States, 78251
      • Roxane Laboratories Research Site #29
    • San Antonio, Texas, United States, 78258
      • Roxane Laboratories Research Site #48
  • Utah
    • West Jordan, Utah, United States, 84088
      • Roxane Laboratories Research Site #42
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Roxane Laboratories Research Site #39
  • Virginia
    • Henrico, Virginia, United States, 23233
      • Roxane Laboratories Research Site #9
    • Richmond, Virginia, United States, 23220
      • Roxane Laboratories Research Site #88
    • Richmond, Virginia, United States, 23235
      • Roxane Laboratories Research Site #18
  • Washington
    • Tacoma, Washington, United States, 98405
      • Roxane Laboratories Research Site #76
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Roxane Laboratories Research Site #82

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects must be 12 years of age or older. Females must be of non-childbearing potential or if of childbearing potential, must commit to consistent use of a form of birth control which is medically effective.
2. Be able to provide written informed consent or, in the case of adolescents, informed assent in addition to an informed consent form signed by the adolescent's parent(s) or legal guardian(s).
3. Be current non-smokers and also may not have used tobacco products (e.g., cigarettes, cigars, pipe tobacco) within the year prior to Visit 1, and have 10 years or less (10 pack-years for cigarettes) of historical use.
4. Have persistent asthma, as defined by the National Asthma Education and Prevention Program, for at least 12 weeks before Visit 1.
5. The forced expiratory volume at one second ("FEV1") range required for enrollment is dependent on whether the subject is an adult or adolescent and whether he or she is currently treated with inhaled corticosteroids ("ICS") at Visit 1
6. Demonstrate 15% or greater reversibility of FEV1 between 10 and 30 minutes following 360 µg of albuterol inhalation. NOTE: If the subject does not meet criterion 6 at Visit 1 (Day -14), this criterion must be met at Visit 2 (Day -1).
7. Be able to discontinue controller asthma medication (including leukotriene modifiers ("LTM"), ICS and long acting β-agonists (LABAs)) during the Run-in Period and Treatment Period.
8. Be able to replace current short-acting β-agonists (SABAs) with the study-supplied albuterol (or equivalent) rescue medication inhaler for use as needed for the duration of the study (subjects should be able to withhold all inhaled SABAs for a least 6 hours before lung function assessments during study visits).

9. Be appropriately using 1 of the following asthma-treatment regimens and meet the associated criteria:

   • Low- to medium-dose ICS for at least 4 weeks before Visit 1, with or without an adjunctive asthma therapy (i.e., LABA, LTM, or theophylline). Both the ICS dose and overall daily asthma regimen must have been stable for the 4 weeks before Visit 1; or
   • Leukotriene modifier (such as montelukast, zafirlukast, or pranlukast) or theophylline as monotherapy at a stable dose for at least 4 weeks before Visit 1;or
   • Daily (or near daily) rescue medication (e.g., albuterol/ salbutamol or other inhaled SABA used to treat acute asthma) in the 4 weeks before Visit 1.
10. Must not have been treated (for any reason) with oral or parenteral corticosteroids for at least 1 month before Visit 1 and must not have used oral SABAs for at least 12 hours before Visit 1 and for the remainder of the study. Routine use of oral/parenteral corticosteroids and oral SABAs is not allowed after Visit 1.
11. Subjects may continue using short-acting forms of theophylline (withheld at least 12 hours before a site visit), twice daily controlled release forms of theophylline (withheld at least 24 hours before a site visit), and once daily controlled-release forms of theophylline (withheld at least 36 hours before a site visit).

12. Be able to answer questions regarding asthma status and be able to document) device usage and asthma status on a twice daily basis.

    NOTE: Placebo inhaler use (i.e., compliance) must be at least 75% of the planned doses taken as assessed at Visit 2, for the subject to be considered eligible to continue in the study.

13. Demonstrate proper use of metered dose inhaler ("MDI") and dry-powder inhaler devices.

Exclusion Criteria:

1. Have an Asthma Control Questionnaire (ACQ) score of 3.0 or greater at Visit 1.
2. Are unable to discontinue ICS, LABA, or LTM.
3. Have a history of life-threatening asthma, defined as an asthma episode (at any time in the past) associated with any of the following: respiratory arrest or intubation, hypercapnia, hypoxic seizures, or syncopal episode.
4. Have exercise-induced asthma as the only asthma-related diagnosis that does not require daily asthma control medicine.
5. Have 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 subject at risk through study participation, or would affect the study analyses if the disease exacerbated during the study.
6. Have current clinical evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
7. Have obstructive sleep apnea severe enough to require biphasic or continuous positive-airway pressure therapy, or likely to interfere with the assessment of asthma symptoms, in the investigator's judgment.
8. Using medication with the potential to affect the course of asthma or interact with sympathomimetic amines (e.g., β blockers [including eye drops], oral decongestants, benzodiazepines, digitalis, phenothiazines, polycyclic antidepressants, monoamine oxidase inhibitors).
9. Had a viral or bacterial, upper or lower respiratory tract infection or sinus or middle ear infection within 4 weeks before Visit 1 or have an infection during the Run-in Period.
10. Participated in an interventional study or used any investigational drug for any disease within 30 days (or 4 half lives, if this is longer than 30 days) before Visit 1 before Visit 1.
11. Used an anti-immunoglobulin E (e.g., omalizumab) or any other monoclonal antibody for any reason within 6 months before Visit 1.
12. Are hypersensitive to any β2-agonist sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy or any component of these combination medications including severe milk protein hypersensitivity.
13. Are exhibiting any factors (e.g., infirmity, disability, or geographic location, inability to follow instructions or study compliance requirements) that the investigator believes would likely limit the subject's compliance with the study protocol or scheduled site visits. This includes recent history of substance abuse or uncontrolled psychiatric or neurological behavior that would render the subject incapable of reliably following study requirements, in the judgment of the investigator.
14. Have an affiliation with the participating site; in other words, subject may not be an immediate family member of any study site staff and may not be employed directly or indirectly by the study site.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone / Salmeterol; fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Vectura lever operated multidose inhaler ("LOMI") inhaler device twice a day by inhalation throughout the study	Drug: Fluticasone / Salmeterol; Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Vectura LOMI inhaler device
Active Comparator: Advair Diskus 100/50; Advair Diskus (fluticasone propionate and salmeterol xinafoate) twice a day by inhalation throughout the study	Drug: Advair Diskus 100/50; Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate administered via the Diskus inhaler device)
Placebo Comparator: placebo inhaler; placebo inhaled powder twice a day by inhalation throughout the study	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Baseline-adjusted area under the serial FEV1-time curve from time 0 to 12 hours on the first day of the Treatment Period	0-12 hours after dosing on Day 1
Baseline-adjusted, pre-dose FEV1 on the last day of the Treatment Period	30 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	From Visit 1 (Day -28) until 30 days after the last dose of study drug

Collaborators and Investigators

• Sponsor: Roxane Laboratories
• Collaborators: Vectura Limited

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 5, 2016
• First Submitted That Met QC Criteria: January 6, 2016
• First Posted (Estimate): January 7, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• 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; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Fluticasone; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: FLSA-P100/50-PVCL-1