Study of Fluticasone Propionate Multidose Dry Powder Inhaler Compared With Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler

Asthma Clinical Trial

Official title:

A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Fluticasone Propionate Multidose Dry Powder Inhaler Compared With Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler in Patients Aged 4 Through 11 Years With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02980133
• Other study ID #: FSS-AS-30003
• Secondary ID: 2016-003835-39
• Status: Completed
• Phase: Phase 3
• Start date: December 28, 2016
• Est. completion date: April 13, 2019

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the safety and efficacy of fluticasone propionate and fluticasone propionate salmeterol in pediatric participants with a documented history of persistent asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 841
• Est. completion date: April 13, 2019
• Est. primary completion date: April 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

Inclusion Criteria:

• The participant has a diagnosis of asthma as defined by the National Institutes of Health (NIH).

• The participant has persistent asthma with a FEV1 =50% and =90% of the value predicted for age, height, sex, and race at the screening visit (SV).

• The participant's persistent asthma is stable and is currently being treated with stable asthma therapy for at least 30 days before the SV. Participants currently on a short-acting ß2-agonist (SABA) only, regimen or as needed (PRN), are not eligible.

• The participant has demonstrated =10% response to a bronchodilator from screening FEV1 within 30 minutes after 2 to 4 inhalations of albuterol/salbutamol.

• The participant (with assistance from parents/legal guardians/caregivers, as needed) is able to perform technically acceptable lung function assessments by handheld device.

• All participants must be able to replace their current SABA with albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) inhalation aerosol at the SV for use as needed for the duration of the study.

• Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

• The participant has a history of life-threatening asthma exacerbation that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, or hypoxic seizures.

• The participant is pregnant or lactating or plans to become pregnant during the study period or within 30 days after the participant's last study-related visit.

• The participant has a known hypersensitivity to any corticosteroid, salmeterol, or any of the excipients in the investigational medicinal product (IMP) or rescue medication formulation (that is, lactose).

• The participant has been treated with any known strong cytochrome P450 (CYP) 3A4 inhibitors (for example, ketoconazole, ritonavir, clarithromycin) within 30 days before the SV or plans to be treated with any strong CYP3A4 inhibitor during the study.

• The participant currently smokes or has a smoking history. The participant must not have used tobacco products within the past year (for example, cigarettes, cigars, chewing tobacco, or pipe tobacco).

• The participant has had an asthma exacerbation requiring systemic corticosteroids within 30 days before the SV or has had any hospitalization for asthma within 2 months before the SV.

• The participant has used immunosuppressive medications within 30 days before the SV.

• The participant has untreated oral candidiasis at the SV. Participants with clinical visual evidence of oral candidiasis who agree to receive treatment and comply with appropriate medical monitoring may enter the run-in period.

• The participant has a history of a positive test for human immunodeficiency virus, active hepatitis B virus, or hepatitis C infection.

• The participant is an immediate relative of an employee of the clinical investigational center.

• A member of the participant's household is participating in the study at the same time.

• Vulnerable participants (that is, people kept in detention) are excluded from participation.

• Additional criteria apply, please contact the investigator for more information

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone Propionate
Fluticasone propionate was administered via MDPI per the dose and schedule specified in the arm.
• Fluticasone Propionate/Salmeterol
Fluticasone propionate/salmeterol was administered via MDPI per the dose and schedule specified in the arm.
• Placebo MDPI
Matching placebo was administered via MDPI per the schedule specified in the arm.

Locations

Country	Name	City	State
Georgia	Teva Investigational Site 81041	Kutaisi
Georgia	Teva Investigational Site 81040	Tbilisi
Georgia	Teva Investigational Site 81042	Tbilisi
Georgia	Teva Investigational Site 81043	Tbilisi
Georgia	Teva Investigational Site 81044	Tbilisi
Georgia	Teva Investigational Site 81045	Tbilisi
Georgia	Teva Investigational Site 81046	Tbilisi
Georgia	Teva Investigational Site 81047	Tbilisi
Hungary	Teva Investigational Site 51272	Budapest
Hungary	Teva Investigational Site 51277	Budapest
Hungary	Teva Investigational Site 51278	Budapest
Hungary	Teva Investigational Site 51279	Debrecen
Hungary	Teva Investigational Site 51271	Dombovar
Hungary	Teva Investigational Site 51269	Gyor
Hungary	Teva Investigational Site 51274	Kaposvar
Hungary	Teva Investigational Site 51270	Miskolc
Hungary	Teva Investigational Site 51276	Szeged
Hungary	Teva Investigational Site 51273	Szigetvar
Russian Federation	Teva Investigational Site 50444	Moscow
Russian Federation	Teva Investigational Site 50446	Perm
Russian Federation	Teva Investigational Site 50443	Saint Petersburg
Russian Federation	Teva Investigational Site 50445	Saint Petersburg
Russian Federation	Teva Investigational Site 50441	Saint-Petersburg
Russian Federation	Teva Investigational Site 50442	Saint-Petersburg
Russian Federation	Teva Investigational Site 50447	Saint-Petersburg
Russian Federation	Teva Investigational Site 50448	Saint-Petersburg
Russian Federation	Teva Investigational Site 50440	Tomsk
Ukraine	Teva Investigational Site 58261	Chernivtsi
Ukraine	Teva Investigational Site 58262	Dnipropetrovsk
Ukraine	Teva Investigational Site 58269	Ivano-Frankivsk
Ukraine	Teva Investigational Site 58270	Kharkiv
Ukraine	Teva Investigational Site 58265	Kryvyi Rih
Ukraine	Teva Investigational Site 58264	Kyiv
Ukraine	Teva Investigational Site 58268	Kyiv
Ukraine	Teva Investigational Site 58271	Kyiv
Ukraine	Teva Investigational Site 58260	Lviv
Ukraine	Teva Investigational Site 58259	Odesa
Ukraine	Teva Investigational Site 58272	Odessa
Ukraine	Teva Investigational Site 58263	Vinnytsya
Ukraine	Teva Investigational Site 58267	Zaporizhzhia
Ukraine	Teva Investigational Site 58266	Zaporizhzhya
United States	Teva Investigational Site 13906	Bakersfield	California
United States	Teva Investigational Site 13898	Baytown	Texas
United States	Teva Investigational Site 13915	Bellingham	Washington
United States	Teva Investigational Site 13881	Birmingham	Alabama
United States	Teva Investigational Site 14673	Boerne	Texas
United States	Teva Investigational Site 13855	Canton	Ohio
United States	Teva Investigational Site 13856	Centennial	Colorado
United States	Teva Investigational Site 13871	Charleston	South Carolina
United States	Teva Investigational Site 13889	Charleston	South Carolina
United States	Teva Investigational Site 13890	Charlotte	North Carolina
United States	Teva Investigational Site 13913	Chiefland	Florida
United States	Teva Investigational Site 13910	Colorado Springs	Colorado
United States	Teva Investigational Site 13865	Columbia	Missouri
United States	Teva Investigational Site 13885	Columbia	Missouri
United States	Teva Investigational Site 14615	Corona	California
United States	Teva Investigational Site 14616	DeLand	Florida
United States	Teva Investigational Site 13892	Downey	California
United States	Teva Investigational Site 13896	Eagle	Idaho
United States	Teva Investigational Site 13867	El Paso	Texas
United States	Teva Investigational Site 13875	Fountain Valley	California
United States	Teva Investigational Site 13866	Gainesville	Georgia
United States	Teva Investigational Site 13909	Homestead	Florida
United States	Teva Investigational Site 13877	Huntington Beach	California
United States	Teva Investigational Site 13904	Huntington Beach	California
United States	Teva Investigational Site 13903	Idaho Falls	Idaho
United States	Teva Investigational Site 13902	Killeen	Texas
United States	Teva Investigational Site 13883	Little Rock	Arkansas
United States	Teva Investigational Site 13846	Live Oak	Texas
United States	Teva Investigational Site 14668	Long Beach	California
United States	Teva Investigational Site 13868	Longmont	Colorado
United States	Teva Investigational Site 13857	Loxahatchee Groves	Florida
United States	Teva Investigational Site 13861	Medford	Oregon
United States	Teva Investigational Site 13864	Miami	Florida
United States	Teva Investigational Site 13872	Miami	Florida
United States	Teva Investigational Site 13880	Miami	Florida
United States	Teva Investigational Site 13886	Miami	Florida
United States	Teva Investigational Site 13893	Miami	Florida
United States	Teva Investigational Site 13899	Miami	Florida
United States	Teva Investigational Site 13907	Miami	Florida
United States	Teva Investigational Site 13870	Miami Lakes	Florida
United States	Teva Investigational Site 14617	Miami Lakes	Florida
United States	Teva Investigational Site 13916	Miami Springs	Florida
United States	Teva Investigational Site 13905	Milford	Ohio
United States	Teva Investigational Site 13891	Missoula	Montana
United States	Teva Investigational Site 13914	Napa	California
United States	Teva Investigational Site 13911	Ocala	Florida
United States	Teva Investigational Site 13897	Ocean City	New Jersey
United States	Teva Investigational Site 13852	Oklahoma City	Oklahoma
United States	Teva Investigational Site 13879	Oklahoma City	Oklahoma
United States	Teva Investigational Site 13884	Oklahoma City	Oklahoma
United States	Teva Investigational Site 13887	Overland Park	Kansas
United States	Teva Investigational Site 13851	Owensboro	Kentucky
United States	Teva Investigational Site 13876	Palmetto Bay	Florida
United States	Teva Investigational Site 13918	Paramount	California
United States	Teva Investigational Site 13874	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 13888	Providence	Rhode Island
United States	Teva Investigational Site 13863	Raleigh	North Carolina
United States	Teva Investigational Site 13850	Richmond	Virginia
United States	Teva Investigational Site 13849	Rockville	Maryland
United States	Teva Investigational Site 14618	Rolling Hills Estates	California
United States	Teva Investigational Site 13912	Roseville	California
United States	Teva Investigational Site 13878	San Antonio	Texas
United States	Teva Investigational Site 13917	San Antonio	Texas
United States	Teva Investigational Site 14672	San Antonio	Texas
United States	Teva Investigational Site 13858	Savannah	Georgia
United States	Teva Investigational Site 13895	Scottdale	Pennsylvania
United States	Teva Investigational Site 13853	Spartanburg	South Carolina
United States	Teva Investigational Site 13882	Springfield	Illinois
United States	Teva Investigational Site 13847	Stockton	California
United States	Teva Investigational Site 14671	Summerville	South Carolina
United States	Teva Investigational Site 13848	Thousand Oaks	California
United States	Teva Investigational Site 13860	Tulsa	Oklahoma
United States	Teva Investigational Site 13894	Tulsa	Oklahoma
United States	Teva Investigational Site 13854	Verona	New Jersey
United States	Teva Investigational Site 13845	Waco	Texas
United States	Teva Investigational Site 13908	Watertown	New York
United States	Teva Investigational Site 13844	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Georgia,  Hungary,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For FS MDPI Versus Fp MDPI: Change From Baseline in 1-Hour Postdose Percent Predicted Morning Forced Expiratory Volume in 1 Second (FEV1) at Week 12	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. The baseline 1-hour trough morning percent predicted FEV1 was defined as the predose trough morning percent predicted FEV1 measurement at the randomization visit (Baseline [Day 1]) at the investigational center. The IMP dose was administered right after the predose FEV1 measurement (within a 10 minute window). Participant then performed 1-hour (±10 minutes) postdose lung function assessments on Week 12 at the investigational center.	Baseline, Week 12
Primary	For Fp MDPI Versus Placebo: Change From Baseline in Weekly Average of the Percent Predicted Trough Morning FEV1 at Week 12	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Baseline trough morning percent predicted FEV1 was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning percent predicted FEV1 measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning FEV1 values divided by the number of nonmissing assessments.	Baseline, Week 12
Secondary	Change From Baseline in the Weekly Average of Daily Trough Morning (Predose and Pre-Rescue Bronchodilator) Peak Expiratory Flow (PEF) Over the 12 Week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Morning PEF was determined in the morning, before administration of IMP or rescue medications. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments.	Baseline, Week 1 to 12
Secondary	Change From Baseline in the Weekly Average of Total Daily (24 Hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1 Through 12	Participants recorded the number of inhalations of rescue medication (albuterol/salbutamol HFA MDI) each morning and evening in the electronic patient diary. An entry of 0 inhalations indicated no rescue medication was needed. To calculate the total daily use of albuterol/salbutamol inhalation aerosol (number of inhalations), the electronic patient diary entry on randomization visit (Baseline [Day 1]) was defined as the first day of analysis. The weekly average of the total daily inhalations was the average based on the available data for that week. The average was calculated as the sum of total daily inhalations over the 7 days for each analysis week divided by the number of nonmissing assessments. LS mean and standard error (SE) were obtained using mixed model for repeated measures (MMRM).	Baseline, Week 1 to 12
Secondary	Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1 Through 12	Asthma symptom scores were recorded in the patient diary. Each participant assessed the symptoms of cough, wheeze, shortness of breath, and chest tightness and entered a single score that was inclusive of all symptoms. Daytime Symptom Score (determined in the evening) ranged from 0=No symptoms during the day to 5=Symptoms so severe that I could not go to work or perform normal daily activities. Nighttime Symptom Score (determined in the morning) ranged from 0=No symptoms during the night to 4=Symptoms so severe that I did not sleep at all. The total daily asthma symptom score was the average of the daytime and nighttime scores. The total daily asthma symptom score ranged from 0 - 9 with 0=no symptoms during the day or night and 9=severe symptoms both day and night. The weekly average was calculated as the sum of total daily asthma symptom scores over the 7 days for each analysis week divided by the number of nonmissing assessments. LS mean and SE were obtained using MMRM.	Baseline, Week 1 to 12
Secondary	Change From Baseline in Asthma Control (Measured by Childhood Asthma Control Test [C-ACT] Score) Over the 12 Week Treatment Period	C-ACT was a simple, participant-completed tool used for the assessment of overall asthma control. The first 4 items of the test were completed by the participant, while the last 3 items were completed by the participant's parents/legal guardians/caregivers. A total sum score based upon responses to all items was calculated to provide an overall measure of asthma control. The derived C-ACT score ranging from 0 to 27. These scores spanned the continuum of poor control of asthma (score =5) to complete control of asthma (score =25), with a cut off score of 19 indicating participants with poorly controlled asthma. LS mean and SE were obtained using MMRM.	Baseline, Week 1 to 12
Secondary	Time to First Onset of Effect	The time to first onset of effect, defined as the first decrease from baseline in daily rescue medication use, was calculated based on the number of inhalations of rescue medication (albuterol/salbutamol hydrofluoroalkane metered-dose inhaler [HFA MDI] [90 mcg ex actuator] or equivalent) recorded by the participant each morning and evening in the patient diary built into the handheld device.	Baseline up to Week 12
Secondary	Percentage of Participants Who Discontinued From Investigational Medicinal Product (IMP) for Asthma Exacerbation During the 12 Week Treatment Period		Baseline up to Week 12