Dose-ranging Study of Vilanterol (VI) Inhalation Powder in Children

Asthma Clinical Trial

Official title:

A Dose-ranging Study of Vilanterol (VI) Inhalation Powder in Children Aged 5-11 Years With Asthma on a Background of Inhaled Corticosteroid Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01573767
• Other study ID #: 106853
• Status: Completed
• Phase: Phase 2
• First received: March 8, 2012
• Last updated: April 2, 2015
• Start date: April 2012
• Est. completion date: April 2014

Study information

• Verified date: March 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Phase IIb, multi-centre, randomised, double-blind, parallel-group, placebo-controlled study in children aged 5-11 years with persistent uncontrolled asthma. Subjects entering the run-in period will stop their current asthma medication and be given open label fluticasone propionate (FP) 100mcg twice daily via DISKUS/ACCUHALER and salbutamol/albuterol as required to use throughout the run-in and double-blind treatment period. At Visit 3 subjects meeting the randomization eligibility criteria will receive vilanterol (6.25mcg, 12.5mcg, or 25mcg,) or placebo via the Novel Dry Powder Inhaler (NDPI) once daily for 4 weeks in addition to open-label fluticasone propionate twice daily throughout the treatment period. Primary endpoints consist of change from baseline in clinic visit trough (pre-bronchodilator and pre-dose) PEF at the end of the 28-day treatment period in all subjects. Safety assessments include adverse events, oropharyngeal examinations, clinical chemistry, 12-lead ECG, and vital signs. Blood samples will be taken from all subjects for pharmacokinetic analysis to determine plasma concentrations of vilanterol at specific time intervals relative to the dose of study drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 463
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 11 Years

Eligibility

Inclusion Criteria:

• Written informed consent from at least one parent/ legal guardian to take part in the study.:

• Diagnosis of asthma

• pre-bronchodilator PEF between =50% to =90% of their best post-bronchodilator value

• Receiving stable asthma therapy of short acting beta-agonist (SABA) plus ICS (total daily dose FP 200mcg or equivalent)

Exclusion Criteria:

• history of life-threatening asthma

• history of asthma exacerbation for asthma within 6 months prior to screening.

• Culture-documented or suspected bacterial or viral infection

• significant abnormality or medical condition

• Present use of any tobacco products

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone propionate 100mcg
all subjects recieve open-label Flovent twice daily duirng the run in and treatment period
• Placebo
Placebo inhalation powder during treatment period
• Vilanterol
subjects will recieve 4 weeks via NDPI during treament period

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Berazategui
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Florencio Varela	Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Nueve de Julio	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario
Argentina	GSK Investigational Site	Salta
Argentina	GSK Investigational Site	Tucuman
Chile	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Viña del Mar
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Germany	GSK Investigational Site	Baunatal-Grossenritte	Hessen
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamm	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kleve-Materborn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Neu isenburg	Hessen
Germany	GSK Investigational Site	Neuhaus am Rennweg	Thueringen
Germany	GSK Investigational Site	Rosenheim	Bayern
Germany	GSK Investigational Site	Wesel	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wolfenbuettel	Niedersachsen
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Wakayama
Mexico	GSK Investigational Site	Mexico city
Mexico	GSK Investigational Site	Puebla, Pue	Puebla
Mexico	GSK Investigational Site	Villahermosa	Tabasco
Mexico	GSK Investigational Site	Zapopan	Jalisco
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima 27	Lima
Peru	GSK Investigational Site	San Miguel	Lima
Peru	GSK Investigational Site	Santiago de Surco	Lima
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
Poland	GSK Investigational Site	Bienkowka
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Olesnica
Poland	GSK Investigational Site	Ostrow Wielkopolski
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Zawadzkie
Puerto Rico	GSK Investigational Site	Hato Rey
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Martin
Slovakia	GSK Investigational Site	Vysoke Tatry
South Africa	GSK Investigational Site	CapeTown
South Africa	GSK Investigational Site	Meyerspark	Gauteng
South Africa	GSK Investigational Site	Middelburg
South Africa	GSK Investigational Site	Panorama
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Zaporizhia
Ukraine	GSK Investigational Site	Zaporizhia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbia	Missouri
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Mission Viejo	California
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Nicholasville	Kentucky
United States	GSK Investigational Site	Normal	Illinois
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Shiloh	Illinois
United States	GSK Investigational Site	South Burlington	Vermont
United States	GSK Investigational Site	Spring	Texas
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Georgia,  Germany,  Japan,  Mexico,  Peru,  Philippines,  Poland,  Puerto Rico,  Slovakia,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Daily Pre-dose Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use each morning. The best of three measurements was recorded. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 4-week Treatment Period minus the Baseline value. The Baseline PEF value is defined as the average of the last 7 days of the Run-in Phase. The analysis was performed using an analysis of covariance (ANCOVA) model with covariates of Baseline, region, sex, age, and treatment. Only those participants contributing data per the daily eDiary were analyzed.	Baseline; Week 1 up to Week 4	No
Secondary	Change From Baseline in Evening Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 4-week Treatment Period in Children Who Could Perform the Maneuver	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as a pre-dose FEV1 measurement taken at a clinic visit while still on treatment. Change from Baseline in trough FEV1 at the end of the 4-week Treatment Period was defined using the pre-dose FEV1 measurement taken at the Week 4 clinic visit. Change from Baseline was calculated as the Week 4 trough FEV1 value minus the Baseline value. The Baseline FEV1 value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline trough FEV1, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.	Baseline; Week 4	No
Secondary	Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 4-week Treatment Period	The number of inhalations of rescue albuterol/salbutamol inhalation aerosol (medication used to relieve symptoms immediately) used during the day and night) was recorded by the participants in a daily diary. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Participants who were rescue free for 24-hour periods during the 4-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline is calculated as the average value during the 4-week Treatment Period minus the value at Baseline. The Baseline value is defined as the value at Visit 3 (randomization). Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.	Baseline; Week 1 up to Week 4	No
Secondary	Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 4-week Treatment Period (at Week 4) minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.	Baseline; Week 1 up to Week 4	No
Secondary	Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4)	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline is calculated as the value over the last 7 days of the Treatment Period minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.	Baseline; Week 4	No
Secondary	Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 4)	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline is calculated as the value of the averaged daily AM PEF over the 4-week Treatment Period (at Week 4) minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.	Baseline; Week 4	No
Secondary	Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 4-week Treatment Period	Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the PEF measurement. A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline symptom-free value is defined as the value at Visit 3 (randomization). Change from Baseline was calculated as the averaged value during the 4-week Treatment Period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.	Baseline; Week 1 up to Week 4	No