Clinical trial NCT02649478: Clinical Endpoint Bioequivalence Study for Fluticasone Propionate and Salmeterol Xinafoate
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Lead sponsor: West-Ward Pharmaceutical
Sponsor class: INDUSTRY
Collaborators: name: Vectura Limited
First posted: 2016-01-07
Enrollment: 1430
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: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Baseline-adjusted area under the serial FEV1-time curve from time 0 to 12 hours on the first day of the Treatment Period
timeFrame: 0-12 hours after dosing on Day 1
measure: Baseline-adjusted, pre-dose FEV1 on the last day of the Treatment Period
timeFrame: 30 Days
Secondary outcomes:
measure: Adverse Events
timeFrame: From Visit 1 (Day -28) until 30 days after the last dose of study drug
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Roxane Laboratories Research Site #30
state: Arizona
city: Phoenix
country: United States
facility: Roxane Laboratories Research Site #46
state: Arizona
city: Surprise
country: United States
facility: Roxane Laboratories Research Site #1
state: Arizona
city: Tempe
country: United States
facility: Roxane Laboratories Research Site #13
state: Arizona
city: Bakersfield
country: United States
facility: Roxane Laboratories Research Site #84
state: California
city: Costa Mesa
country: United States
facility: Roxane Laboratories Research Site #72
state: California
city: Encinitas
country: United States
facility: Roxane Laboratories Research Site #67
state: California
city: Fountain Valley
country: United States
facility: Roxane Laboratories Research Site #4
state: California
city: Fullerton
country: United States
facility: Roxane Laboratories Research Site #64
state: California
city: Huntington Beach
country: United States
facility: Roxane Laboratories Research Site #3
state: California
city: Huntington Beach
country: United States
facility: Roxane Laboratories Research Site #70
state: California
city: Huntington Beach
country: United States
facility: Roxane Laboratories Research Site #92
state: California
city: Irvine
country: United States
facility: Roxane Laboratories Research Site #38
state: California
city: Lincoln
country: United States
facility: Roxane Laboratories Research Site #91
state: California
city: Los Angeles
country: United States
facility: Roxane Laboratories Research Site #59
state: California
city: Los Angeles
country: United States
facility: Roxane Laboratories Research Site #16
state: California
city: Los Angeles
country: United States
facility: Roxane Laboratories Research Site #90
state: California
city: Mission Viejo
country: United States
facility: Roxane Laboratories Research Site #6
state: California
city: Rolling Hills Estates
country: United States
facility: Roxane Laboratories Research Site #78
state: California
city: Sacramento
country: United States
facility: Roxane Laboratories Research Site #98
state: California
city: San Diego
country: United States
facility: Roxane Laboratories Research Site #53
state: California
city: San Diego
country: United States
facility: Roxane Laboratories Research Site #93
state: California
city: San Jose
country: United States
facility: Roxane Laboratories Research Site #28
state: California
city: Santa Monica
country: United States
facility: Roxane Laboratories Research Site #60
state: California
city: Centennial
country: United States
facility: Roxane Laboratories Research Site #33
state: Colorado
city: Denver
country: United States
facility: Roxane Laboratories Research Site #43
state: Colorado
city: Denver
country: United States
facility: Roxane Laboratories Research Site #63
state: Colorado
city: Wheat Ridge
country: United States
facility: Roxane Laboratories Research Site #21
state: Colorado
city: Hialeah
country: United States
facility: Roxane Laboratories Research Site #50
state: Florida
city: Hialeah
country: United States
facility: Roxane Laboratories Research Site #11
state: Florida
city: Homestead
country: United States
facility: Roxane Laboratories Research Site #66
state: Florida
city: Jupiter
country: United States
facility: Roxane Laboratories Research Site #83
state: Florida
city: Miami
country: United States
facility: Roxane Laboratories Research Site #8
state: Florida
city: Miami
country: United States
facility: Roxane Laboratories Research Site #23
state: Florida
city: Miami
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facility: Roxane Laboratories Research Site #86
state: Florida
city: Miami
country: United States
facility: Roxane Laboratories Research Site #89
state: Florida
city: Miami
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state: Florida
city: Miami
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facility: Roxane Laboratories Research Site #68
state: Florida
city: Miami
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facility: Roxane Laboratories Research Site #80
state: Florida
city: Miami
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facility: Roxane Laboratories Research Site #54
state: Florida
city: Miami
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state: Florida
city: Orlando
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state: Florida
city: Port Orange
country: United States
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state: Florida
city: Lilburn
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state: Georgia
city: Rincon
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state: Georgia
city: Normal
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facility: Roxane Laboratories Research Site #79
state: Illinois
city: River Forest
country: United States
facility: Roxane Laboratories Research Site #47
state: Illinois
city: Brownsburg
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facility: Roxane Laboratories Research Site #100
state: Indiana
city: Baltimore
country: United States
facility: Roxane Laboratories Research Site #62
state: Maryland
city: Baltimore
country: United States
facility: Roxane Laboratories Research Site #52
state: Maryland
city: Bethesda
country: United States
facility: Roxane Laboratories Research Site #71
state: Maryland
city: Silver Spring
country: United States
facility: Roxane Laboratories Research Site #96
state: Maryland
city: Fall River
country: United States
facility: Roxane Laboratories Research Site #81
state: Massachusetts
city: North Dartmouth
country: United States
facility: Roxane Laboratories Research Site #56
state: Massachusetts
city: Ann Arbor
country: United States
facility: Roxane Laboratories Research Site #55
state: Michigan
city: Chelsea
country: United States
facility: Roxane Laboratories Research Site #97
state: Michigan
city: Plymouth
country: United States
facility: Roxane Laboratories Research Site #5
state: Minnesota
city: Saint Louis
country: United States
facility: Roxane Laboratories Research Site #85
state: Missouri
city: Bellevue
country: United States
facility: Roxane Laboratories Research Site #32
state: Nebraska
city: Bellevue
country: United States
facility: Roxane Laboratories Research Site #25
state: Nebraska
city: Omaha
country: United States
facility: Roxane Laboratories Research Site #36
state: Nebraska
city: Las Vegas
country: United States
facility: Roxane Laboratories Research Site #57
state: Nevada
city: Atco
country: United States
facility: Roxane Laboratories Research Site #10
state: New Jersey
city: Skillman
country: United States
facility: Roxane Laboratories Research Site #65
state: New Jersey
city: New York
country: United States
facility: Roxane Laboratories Research Site #7
state: New York
city: New York
country: United States
facility: Roxane Laboratories Research Site #2
state: New York
city: Clemmons
country: United States
facility: Roxane Laboratories Research Site #41
state: North Carolina
city: Raleigh
country: United States
facility: Roxane Laboratories Research Site #45
state: North Carolina
city: Cincinnati
country: United States
facility: Roxane Laboratories Research Site #31
state: Ohio
city: Columbus
country: United States
facility: Roxane Laboratories Research Site #95
state: Ohio
city: Hilliard
country: United States
facility: Roxane Laboratories Research Site #24
state: Ohio
city: Middleburg Heights
country: United States
facility: Roxane Laboratories Research Site #61
state: Ohio
city: Toledo
country: United States
facility: Roxane Laboratories Research Site #73
state: Ohio
city: Edmond
country: United States
facility: Roxane Laboratories Research Site #14
state: Oklahoma
city: Oklahoma City
country: United States
facility: Roxane Laboratories Research Site #15
state: Oklahoma
city: Eugene
country: United States
facility: Roxane Laboratories Research Site #37
state: Oregon
city: Medford
country: United States
facility: Roxane Laboratories Research Site #40
state: Oregon
city: Portland
country: United States
facility: Roxane Laboratories Research Site #58
state: Oregon
city: Warwick
country: United States
facility: Roxane Laboratories Research Site #26
state: Rhode Island
city: Warwick
country: United States
facility: Roxane Laboratories Research Site #99
state: Rhode Island
city: Greenville
country: United States
facility: Roxane Laboratories Research Site #69
state: South Carolina
city: Spartanburg
country: United States
facility: Roxane Laboratories Research Site #22
state: South Carolina
city: Smyrna
country: United States
facility: Roxane Laboratories Research Site #19
state: Tennessee
city: Boerne
country: United States
facility: Roxane Laboratories Research Site #27
state: Texas
city: Dallas
country: United States
facility: Roxane Laboratories Research Site #75
state: Texas
city: El Paso
country: United States
facility: Roxane Laboratories Research Site #49
state: Texas
city: Houston
country: United States
facility: Roxane Laboratories Research Site #44
state: Texas
city: Lewisville
country: United States
facility: Roxane Laboratories Research Site #77
state: Texas
city: Plano
country: United States
facility: Roxane Laboratories Research Site #87
state: Texas
city: San Antonio
country: United States
facility: Roxane Laboratories Research Site #29
state: Texas
city: San Antonio
country: United States
facility: Roxane Laboratories Research Site #48
state: Texas
city: West Jordan
country: United States
facility: Roxane Laboratories Research Site #42
state: Utah
city: South Burlington
country: United States
facility: Roxane Laboratories Research Site #39
state: Vermont
city: Henrico
country: United States
facility: Roxane Laboratories Research Site #9
state: Virginia
city: Richmond
country: United States
facility: Roxane Laboratories Research Site #88
state: Virginia
city: Richmond
country: United States
facility: Roxane Laboratories Research Site #18
state: Virginia
city: Tacoma
country: United States
facility: Roxane Laboratories Research Site #76
state: Washington
city: Greenfield
country: United States
facility: Roxane Laboratories Research Site #82
state: Wisconsin
Study officials:
References: