Clinical Endpoint Bioequivalence Study for Fluticasone Propionate and Salmeterol Xinafoate

Sponsor

Roxane Laboratories (Industry)

Overall Status

Completed

CT.gov ID

NCT02649478

Collaborator

Vectura Limited (Industry)

1,430

Enrollment

100

Locations

Arms

Duration (Months)

14.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fluticasone / Salmeterol Drug: Placebo Drug: Advair Diskus 100/50	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

1430 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Nov 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Adverse Events [From Visit 1 (Day -28) until 30 days after the last dose of study drug]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
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).
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.
Have persistent asthma, as defined by the National Asthma Education and Prevention Program, for at least 12 weeks before Visit 1.
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
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).
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.
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).
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.

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.
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).
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.

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

Exclusion Criteria:

Have an Asthma Control Questionnaire (ACQ) score of 3.0 or greater at Visit 1.
Are unable to discontinue ICS, LABA, or LTM.
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.
Have exercise-induced asthma as the only asthma-related diagnosis that does not require daily asthma control medicine.
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.
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.
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.
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).
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.
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.
Used an anti-immunoglobulin E (e.g., omalizumab) or any other monoclonal antibody for any reason within 6 months before Visit 1.
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.
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.
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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

Roxane Laboratories
Vectura Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Roxane Laboratories

ClinicalTrials.gov Identifier:

NCT02649478

Other Study ID Numbers:

FLSA-P100/50-PVCL-1

First Posted:

Jan 7, 2016

Last Update Posted:

Jan 23, 2018

Last Verified:

Jan 1, 2018

Additional relevant MeSH terms:

Asthma

Fluticasone

Salmeterol Xinafoate

Fluticasone-Salmeterol Drug Combination

Study Results

No Results Posted as of Jan 23, 2018