Clinical Endpoint Bioequivalence Study for Fluticasone Propionate and Salmeterol Xinafoate

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02649478
• Other study ID #: FLSA-P100/50-PVCL-1
• Status: Completed
• Phase: N/A
• First received: January 5, 2016
• Last updated: January 19, 2018
• Start date: August 2014
• Est. completion date: November 2015

Study information

• Verified date: January 2018
• Source: West-Ward Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1430
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 ß-agonists (LABAs)) during the Run-in Period and Treatment Period.

8. Be able to replace current short-acting ß-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., ß 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 ß2-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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone / Salmeterol
Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Vectura LOMI inhaler device
• Placebo

• Advair Diskus 100/50
Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate administered via the Diskus inhaler device)

Locations

Country	Name	City	State
United States	Roxane Laboratories Research Site #55	Ann Arbor	Michigan
United States	Roxane Laboratories Research Site #10	Atco	New Jersey
United States	Roxane Laboratories Research Site #84	Bakersfield	California
United States	Roxane Laboratories Research Site #52	Baltimore	Maryland
United States	Roxane Laboratories Research Site #62	Baltimore	Maryland
United States	Roxane Laboratories Research Site #25	Bellevue	Nebraska
United States	Roxane Laboratories Research Site #32	Bellevue	Nebraska
United States	Roxane Laboratories Research Site #71	Bethesda	Maryland
United States	Roxane Laboratories Research Site #27	Boerne	Texas
United States	Roxane Laboratories Research Site #100	Brownsburg	Indiana
United States	Roxane Laboratories Research Site #33	Centennial	Colorado
United States	Roxane Laboratories Research Site #97	Chelsea	Michigan
United States	Roxane Laboratories Research Site #31	Cincinnati	Ohio
United States	Roxane Laboratories Research Site #41	Clemmons	North Carolina
United States	Roxane Laboratories Research Site #95	Columbus	Ohio
United States	Roxane Laboratories Research Site #72	Costa Mesa	California
United States	Roxane Laboratories Research Site #75	Dallas	Texas
United States	Roxane Laboratories Research Site #43	Denver	Colorado
United States	Roxane Laboratories Research Site #63	Denver	Colorado
United States	Roxane Laboratories Research Site #14	Edmond	Oklahoma
United States	Roxane Laboratories Research Site #49	El Paso	Texas
United States	Roxane Laboratories Research Site #67	Encinitas	California
United States	Roxane Laboratories Research Site #37	Eugene	Oregon
United States	Roxane Laboratories Research Site #81	Fall River	Massachusetts
United States	Roxane Laboratories Research Site #4	Fountain Valley	California
United States	Roxane Laboratories Research Site #64	Fullerton	California
United States	Roxane Laboratories Research Site #30	Glendale	Arizona
United States	Roxane Laboratories Research Site #82	Greenfield	Wisconsin
United States	Roxane Laboratories Research Site #69	Greenville	South Carolina
United States	Roxane Laboratories Research Site #9	Henrico	Virginia
United States	Roxane Laboratories Research Site #11	Hialeah	Florida
United States	Roxane Laboratories Research Site #50	Hialeah	Florida
United States	Roxane Laboratories Research Site #24	Hilliard	Ohio
United States	Roxane Laboratories Research Site #66	Homestead	Florida
United States	Roxane Laboratories Research Site #44	Houston	Texas
United States	Roxane Laboratories Research Site #3	Huntington Beach	California
United States	Roxane Laboratories Research Site #70	Huntington Beach	California
United States	Roxane Laboratories Research Site #92	Huntington Beach	California
United States	Roxane Laboratories Research Site #38	Irvine	California
United States	Roxane Laboratories Research Site #83	Jupiter	Florida
United States	Roxane Laboratories Research Site #57	Las Vegas	Nevada
United States	Roxane Laboratories Research Site #77	Lewisville	Texas
United States	Roxane Laboratories Research Site #34	Lilburn	Georgia
United States	Roxane Laboratories Research Site #91	Lincoln	California
United States	Roxane Laboratories Research Site #16	Los Angeles	California
United States	Roxane Laboratories Research Site #59	Los Angeles	California
United States	Roxane Laboratories Research Site #90	Los Angeles	California
United States	Roxane Laboratories Research Site #40	Medford	Oregon
United States	Roxane Laboratories Research Site #12	Miami	Florida
United States	Roxane Laboratories Research Site #20	Miami	Florida
United States	Roxane Laboratories Research Site #23	Miami	Florida
United States	Roxane Laboratories Research Site #54	Miami	Florida
United States	Roxane Laboratories Research Site #68	Miami	Florida
United States	Roxane Laboratories Research Site #8	Miami	Florida
United States	Roxane Laboratories Research Site #80	Miami	Florida
United States	Roxane Laboratories Research Site #86	Miami	Florida
United States	Roxane Laboratories Research Site #89	Miami	Florida
United States	Roxane Laboratories Research Site #61	Middleburg Heights	Ohio
United States	Roxane Laboratories Research Site #6	Mission Viejo	California
United States	Roxane Laboratories Research Site #2	New York	New York
United States	Roxane Laboratories Research Site #7	New York	New York
United States	Roxane Laboratories Research Site #79	Normal	Illinois
United States	Roxane Laboratories Research Site #56	North Dartmouth	Massachusetts
United States	Roxane Laboratories Research Site #74	North Miami Beach	Florida
United States	Roxane Laboratories Research Site #15	Oklahoma City	Oklahoma
United States	Roxane Laboratories Research Site #36	Omaha	Nebraska
United States	Roxane Laboratories Research Site #17	Orlando	Florida
United States	Roxane Laboratories Research Site #35	Orlando	Florida
United States	Roxane Laboratories Research Site #46	Phoenix	Arizona
United States	Roxane Laboratories Research Site #87	Plano	Texas
United States	Roxane Laboratories Research Site #5	Plymouth	Minnesota
United States	Roxane Laboratories Research Site #94	Port Orange	Florida
United States	Roxane Laboratories Research Site #58	Portland	Oregon
United States	Roxane Laboratories Research Site #45	Raleigh	North Carolina
United States	Roxane Laboratories Research Site #18	Richmond	Virginia
United States	Roxane Laboratories Research Site #88	Richmond	Virginia
United States	Roxane Laboratories Research Site #51	Rincon	Georgia
United States	Roxane Laboratories Research Site #47	River Forest	Illinois
United States	Roxane Laboratories Research Site #78	Rolling Hills Estates	California
United States	Roxane Laboratories Research Site #98	Sacramento	California
United States	Roxane Laboratories Research Site #85	Saint Louis	Missouri
United States	Roxane Laboratories Research Site #29	San Antonio	Texas
United States	Roxane Laboratories Research Site #48	San Antonio	Texas
United States	Roxane Laboratories Research Site #53	San Diego	California
United States	Roxane Laboratories Research Site #93	San Diego	California
United States	Roxane Laboratories Research Site #28	San Jose	California
United States	Roxane Laboratories Research Site #60	Santa Monica	California
United States	Roxane Laboratories Research Site #96	Silver Spring	Maryland
United States	Roxane Laboratories Research Site #65	Skillman	New Jersey
United States	Roxane Laboratories Research Site #19	Smyrna	Tennessee
United States	Roxane Laboratories Research Site #39	South Burlington	Vermont
United States	Roxane Laboratories Research Site #22	Spartanburg	South Carolina
United States	Roxane Laboratories Research Site #1	Surprise	Arizona
United States	Roxane Laboratories Research Site #76	Tacoma	Washington
United States	Roxane Laboratories Research Site #13	Tempe	Arizona
United States	Roxane Laboratories Research Site #73	Toledo	Ohio
United States	Roxane Laboratories Research Site #26	Warwick	Rhode Island
United States	Roxane Laboratories Research Site #99	Warwick	Rhode Island
United States	Roxane Laboratories Research Site #42	West Jordan	Utah
United States	Roxane Laboratories Research Site #21	Wheat Ridge	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
Roxane Laboratories	Vectura Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Baseline-adjusted, pre-dose FEV1 on the last day of the Treatment Period		30 Days
Secondary	Adverse Events		From Visit 1 (Day -28) until 30 days after the last dose of study drug