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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone propionate 100mcg; Drug: Vilanterol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 463
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Berazategui, Argentina, 1886
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1425BEN
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
    • GSK Investigational Site
  • Mendoza, Argentina, M5500CCG
    • GSK Investigational Site
  • Rosario, Argentina, S2000BRH
    • GSK Investigational Site
  • Salta, Argentina, A4400ERH
    • GSK Investigational Site
  • Tucuman, Argentina, 4000
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, C1431FWO
      • GSK Investigational Site
    • Florencio Varela, Buenos Aires, Argentina, 1888
      • GSK Investigational Site
    • La Plata, Buenos Aires, Argentina, 1900
      • GSK Investigational Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • GSK Investigational Site
    • Nueve de Julio, Buenos Aires, Argentina, B6500BWQ
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DBS
      • GSK Investigational Site
    • Rosario, Santa Fe, Argentina, S2000JKR
      • GSK Investigational Site
• Chile
  • Santiago, Chile, 8380453
    • GSK Investigational Site
  • Viña del Mar, Chile, 2520594
    • GSK Investigational Site
  • Región Metro De Santiago
    • Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7520349
      • GSK Investigational Site
• Georgia
  • Tbilisi, Georgia, 0159
    • GSK Investigational Site
  • Tbilisi, Georgia, 0160
    • GSK Investigational Site
  • Tbilisi, Georgia, 0186
    • GSK Investigational Site
  • Tbilisi, Georgia, 0119
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10785
    • GSK Investigational Site
  • Hamburg, Germany, 22415
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Mannheim, Baden-Wuerttemberg, Germany, 68163
      • GSK Investigational Site
  • Bayern
    • Rosenheim, Bayern, Germany, 83026
      • GSK Investigational Site
  • Hessen
    • Baunatal-Grossenritte, Hessen, Germany, 34225
      • GSK Investigational Site
    • Frankfurt am Main, Hessen, Germany, 60596
      • GSK Investigational Site
    • Neu isenburg, Hessen, Germany, 63263
      • GSK Investigational Site
  • Niedersachsen
    • Wolfenbuettel, Niedersachsen, Germany, 38302
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • GSK Investigational Site
    • Hamm, Nordrhein-Westfalen, Germany, 59063
      • GSK Investigational Site
    • Kleve-Materborn, Nordrhein-Westfalen, Germany, 47533
      • GSK Investigational Site
    • Wesel, Nordrhein-Westfalen, Germany, 46483
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Koblenz, Rheinland-Pfalz, Germany, 56068
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04178
      • GSK Investigational Site
  • Schleswig-Holstein
    • Geesthacht, Schleswig-Holstein, Germany, 21502
      • GSK Investigational Site
  • Thueringen
    • Neuhaus am Rennweg, Thueringen, Germany, 98724
      • GSK Investigational Site
• Japan
  • Chiba, Japan, 260-0001
    • GSK Investigational Site
  • Chiba, Japan, 273-0035
    • GSK Investigational Site
  • Fukuoka, Japan, 811-1394
    • GSK Investigational Site
  • Hiroshima, Japan, 720-8520
    • GSK Investigational Site
  • Hokkaido, Japan, 006-0831
    • GSK Investigational Site
  • Hokkaido, Japan, 064-0821
    • GSK Investigational Site
  • Hyogo, Japan, 653-0021
    • GSK Investigational Site
  • Kagawa, Japan, 762-0031
    • GSK Investigational Site
  • Tokyo, Japan, 154-0017
    • GSK Investigational Site
  • Tokyo, Japan, 157-0066
    • GSK Investigational Site
  • Tokyo, Japan, 158-0097
    • GSK Investigational Site
  • Wakayama, Japan, 646-8558
    • GSK Investigational Site
• Mexico
  • Mexico city, Mexico, 04530
    • GSK Investigational Site
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45040
      • GSK Investigational Site
  • Puebla
    • Puebla, Pue, Puebla, Mexico, 72000
      • GSK Investigational Site
  • Tabasco
    • Villahermosa, Tabasco, Mexico, 86100
      • GSK Investigational Site
• Peru
  • Lima, Peru, Lima 1
    • GSK Investigational Site
  • Lima, Peru, Lima 27
    • GSK Investigational Site
  • Lima
    • Lima 27, Lima, Peru, Lima 27
      • GSK Investigational Site
    • San Miguel, Lima, Peru, Lima 32
      • GSK Investigational Site
    • Santiago de Surco, Lima, Peru, Lima 33
      • GSK Investigational Site
• Philippines
  • Cebu City, Philippines, 6000
    • GSK Investigational Site
  • Manila, Philippines, 1000
    • GSK Investigational Site
  • Quezon City, Philippines, 1113
    • GSK Investigational Site
  • Quezon City, Philippines, 1100
    • GSK Investigational Site
• Poland
  • Bienkowka, Poland, 34-212
    • GSK Investigational Site
  • Bydgoszcz, Poland, 85-096
    • GSK Investigational Site
  • Krakow, Poland, 31-159
    • GSK Investigational Site
  • Lublin, Poland, 20-093
    • GSK Investigational Site
  • Olesnica, Poland, 56-400
    • GSK Investigational Site
  • Ostrow Wielkopolski, Poland, 63-400
    • GSK Investigational Site
  • Siemianowice Slaskie, Poland, 41-103
    • GSK Investigational Site
  • Wroclaw, Poland, 50-445
    • GSK Investigational Site
  • Wroclaw, Poland, 51-511
    • GSK Investigational Site
  • Zawadzkie, Poland, 47-120
    • GSK Investigational Site
• Puerto Rico
  • Hato Rey, Puerto Rico, 00917
    • GSK Investigational Site
• Slovakia
  • Bratislava, Slovakia, 826 05
    • GSK Investigational Site
  • Martin, Slovakia, 036 59
    • GSK Investigational Site
  • Vysoke Tatry, Slovakia, 059 81
    • GSK Investigational Site
• South Africa
  • CapeTown, South Africa, 7764
    • GSK Investigational Site
  • Middelburg, South Africa, 1501
    • GSK Investigational Site
  • Panorama, South Africa, 7500
    • GSK Investigational Site
  • Gauteng
    • Meyerspark, Gauteng, South Africa, 0184
      • GSK Investigational Site
• Ukraine
  • Kharkiv, Ukraine, 61093
    • GSK Investigational Site
  • Kyiv, Ukraine, 03680
    • GSK Investigational Site
  • Kyiv, Ukraine, 04050
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69063
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69076
    • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • GSK Investigational Site
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • GSK Investigational Site
  • California
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
    • Long Beach, California, United States, 90808
      • GSK Investigational Site
    • Mission Viejo, California, United States, 92691
      • GSK Investigational Site
    • Newport Beach, California, United States, 92663
      • GSK Investigational Site
    • Orange, California, United States, 92868
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
    • Tampa, Florida, United States, 33613
      • GSK Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31406
      • GSK Investigational Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • GSK Investigational Site
    • Shiloh, Illinois, United States, 62269
      • GSK Investigational Site
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • GSK Investigational Site
  • Kentucky
    • Nicholasville, Kentucky, United States, 40356
      • GSK Investigational Site
  • Maryland
    • White Marsh, Maryland, United States, 21162
      • GSK Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65203
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68107
      • GSK Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
    • Dayton, Ohio, United States, 45414
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • GSK Investigational Site
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78750
      • GSK Investigational Site
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site
    • Spring, Texas, United States, 77379
      • GSK Investigational Site
    • Waco, Texas, United States, 76712
      • GSK Investigational Site
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm 1; Vilanterol 25mcg inhalation powder inhaled once daily in the PM via the new powder inhaler	Drug: Fluticasone propionate 100mcg; all subjects recieve open-label Flovent twice daily duirng the run in and treatment period; Drug: Vilanterol; subjects will recieve 4 weeks via NDPI during treament period
ACTIVE_COMPARATOR: Arm 2; Vilanterol 12.5mcg inhalation powder inhaled once daily in the PM via the new powder inhaler	Drug: Fluticasone propionate 100mcg; all subjects recieve open-label Flovent twice daily duirng the run in and treatment period; Drug: Vilanterol; subjects will recieve 4 weeks via NDPI during treament period
ACTIVE_COMPARATOR: Arm 3; Vilanterol 6.25mcg inhalation powder inhaled once daily in the PM via the new powder inhaler	Drug: Fluticasone propionate 100mcg; all subjects recieve open-label Flovent twice daily duirng the run in and treatment period; Drug: Vilanterol; subjects will recieve 4 weeks via NDPI during treament period
PLACEBO_COMPARATOR: Arm 4; Placebo inhalation powder inhaled once daily in the PM via the new powder inhaler	Drug: Fluticasone propionate 100mcg; all subjects recieve open-label Flovent twice daily duirng the run in and treatment period; Drug: Placebo; Placebo inhalation powder during treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Oliver AJ, Covar RA, Goldfrad CH, Klein RM, Pedersen SE, Sorkness CA, Tomkins SA, Villaran C, Grigg J. Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy. Respir Res. 2016 Apr 5;17:37. doi: 10.1186/s12931-016-0353-4.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: March 8, 2012
• First Submitted That Met QC Criteria: April 5, 2012
• First Posted (ESTIMATE): April 10, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 106853

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 106853
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register