This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Evaluate the Safety, Efficacy and Dose Response of GSK573719 in Combination With Fluticasone Furoate in Subjects With Asthma (ILA115938)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01573624
First received: April 5, 2012
Last updated: July 14, 2017
Last verified: May 2017
  Purpose

Brief Summary: The purpose of this study is to characterize the dose response of GSK573719 in combination with Fluticasone furoate 100mcg in patients with asthma. Treatment with inhaled Fluticasone furoate and Fluticasone furoate/Vilanterol are included as an active control.

Detailed Description: Long acting muscarinic receptor antagonists (anti-cholinergic bronhcodilator) exert their effects via distinct and complementary bronchodilator mechanisms on large and small airways. Most of the experience with older anti-cholinergics had been with acute use and little is known about their effect in chronic use in asthma. This is a multicenter, randomized, double-blind, crossover study to evaluate 5 doses of inhaled GSK573719 inhaled over 14 days in patients with asthma. Fluticasone furoate (100 mcg) and Fluticasone furoate/Vilanterol (100/59mcg) will be included as an active comparator. Each eligible subject will receive a sequence of 3 of 7 potential treatments for a total of 3 treatment periods per subject. The total duration of subject participation is approximately 14 weeks.


Condition Intervention Phase
Asthma Drug: FF/GSK573719 Drug: FF Drug: FF/VI Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: A Multi-center, Randomized, Double-blind, Dose-ranging Study to Evaluate GSK573719 in Combination With Fluticasone Furoate, Fluticasone Furoate Alone, and an Active Control of Fluticasone Furoate/Vilanterol Combination in Subjects With Asthma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Model Predicted Change From Baseline Trough Force Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline (Day 1) and Day 15 of each treatment period ]
    FEV1 is a lung function measure defined as the maximal amount of air that can be forcefully exhaled in one second. Highest FEV1 from the 3 acceptable spirometric efforts were recorded between 5.00 ante meridiem (AM) and 11.00 AM after withholding albuterol (salbutamol) at all visits for at least 4 hours. Baseline was defined as the pre- dose FEV1 value obtained on Day 1 and trough was defined as FEV1 value obtained 24 hours after morning dosing on Day 14 of each treatment period. Change from baseline value for each participant in each treatment period was the difference between the observed on-treatment value obtained 24 hours after morning dosing on Day 14 and the baseline value for that period. Slope-intercept on log dose model was used to predict trough FEV1 change from baseline for each of the FF+UMEC doses adjusted by FF 100 mcg alone. Mean value for the expected response and associated 95% confidence interval (CI) in change from baseline trough FEV1 is presented.

  • Percentage of Chance That FF 100 mcg Alone Corrected Change From Baseline FEV1 Response Would Exceed a Target Response by Dose of UMEC Combined With FF 100 mcg [ Time Frame: Baseline (Day 1) and Day 15 of each treatment period ]
    FEV1 is a lung function measure defined as the maximal amount of air that can be forcefully exhaled in one second. Highest FEV1 from the 3 acceptable spirometric efforts were recorded between 5.00 AM and 11.00 AM after withholding albuterol (salbutamol) at all visits for at least 4 hours. Baseline was defined as the pre- dose FEV1 value obtained on Day 1 and trough was defined as FEV1 value obtained 24 hours after morning dosing on Day 14 of each treatment period. Change from baseline value for each participant in each treatment period was the difference between the observed on-treatment value obtained 24 hours after morning dosing on Day 14 and the baseline value for that period. Data is presented as percentage chance that FF 100 mcg alone corrected change from baseline trough FEV1 response would exceed a target response of 50 mL, 75 mL, 100 mL and 150 mL by doses of UMEC combined with FF 100 mcg.

  • Mean Change From Baseline in Trough FEV1 on Day 15 of Each of the 3 Treatment Periods [ Time Frame: Baseline (Day 1) and Day 15 of each treatment period ]
    FEV1 is a lung function measure defined as the maximal amount of air that can be forcefully exhaled in one second. The highest FEV1 from the 3 acceptable spirometric efforts were recorded between 5.00 AM and 11.00 AM after withholding albuterol (salbutamol) at all visits for at least 4 hours. Baseline was defined as the pre- dose FEV1 value obtained on Day 1 and trough was defined as the FEV1 value obtained 24 hours after morning dosing on Day 14 of each treatment period. The change from baseline value for each participant in each treatment period was the difference between the observed on-treatment value obtained 24 hours after morning dosing on Day 14 and the baseline value for that period. Analysis was done using a mixed model, including treatment, period, period baseline FEV1, and mean baseline FEV1 as fixed effects and participant as a random effect. A post hoc analysis was performed to confirm nullification of carry over effect of UMEC.


Secondary Outcome Measures:
  • Mean Change From Baseline in Daily Morning (Pre-dose and Pre-rescue Bronchodilator) Peak Expiratory Flow (PEF) of Each Treatment Period [ Time Frame: Baseline (Week 0) and last 7 days of each treatment period ]
    PEF is a measure of lung function and measures how fast a person can breathe out. Morning PEF was measured pre-dose and pre- rescue bronchodilator use with an electronic Peak Flow Meter. Participants were issued an electronic diary (eDiary) for daily use throughout the study and instructed on how to complete it. Best of 3 attempts were recorded in eDiary. Mean change from baseline was calculated where, baseline was defined as the measurement from (Week 0), includes Day 1 and six days immediately preceding Day 1 for each treatment period. The change from baseline values for each participant in each treatment period were differences between on-treatment week (last 7 days of each treatment period) values and baseline week. Analysis was done using a mixed model, including treatment, period, period baseline morning PEF and mean baseline morning PEF as fixed effects and participant as a random effect. A post hoc analysis was performed to confirm nullification of carry over effect of UMEC.

  • Mean Change From Baseline in Daily Evening (Pre-dose and Pre-rescue Bronchodilator) PEF of Each Treatment Period [ Time Frame: Baseline (Week 0) and last 7 days of each treatment period ]
    PEF is a measure of lung function and measures how fast a person can breathe out. Evening PEF was measured pre-dose and pre-rescue bronchodilator use with an electronic Peak Flow Meter. Participants were issued an electronic diary (eDiary) for daily use throughout the study and instructed on how to complete it. Best of 3 attempts were recorded in eDiary. Mean change from baseline was calculated where, baseline was defined as the measurement from (Week 0), includes Day 1 and seven days immediately preceding Day 1 for each treatment period. The change from baseline values for each participant in each treatment period were differences between on-treatment week (last 7 days of each treatment period) values and baseline week. Analysis was done using a mixed model, including treatment, period, period baseline evening PEF and mean baseline evening PEF as fixed effects and participant as a random effect. A post hoc analysis was performed to confirm nullification of carry over effect of UMEC.

  • Mean Change From Baseline in Rescue Albuterol/Salbutamol Use of Each Treatment Period. [ Time Frame: Baseline (Week 0) and last 7 days of each treatment period ]
    Short-Acting Beta2-Agonists albuterol/salbutamol was provided to participants as rescue medication, to use in morning and evening. Participants recorded number of puffs of salbutamol MDI used in last 24 hours (sum of night time and day time puffs) daily for relief of symptoms in eDiary. Mean change from baseline was calculated where, baseline was defined as measurement from (Week 0), includes Day 1 and six days immediately preceding Day 1 (for night time puffs) and seven days (for day time puffs) for each treatment period. Change from baseline values for each participant in each treatment period were differences between on-treatment week (last 7 days of each treatment period) values and the baseline week. Analysis was done using a mixed model, including treatment, period, period baseline rescue albuterol use, and mean baseline rescue albuterol use as fixed effects and participant as random effect. A post hoc analysis was performed to confirm nullification of carry over effect of UMEC.


Enrollment: 421
Actual Study Start Date: April 3, 2012
Study Completion Date: February 4, 2013
Primary Completion Date: February 4, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fluticasone Furoate (FF)
100mcg, inhaled
Drug: FF
100
Active Comparator: Fluticasone Furoate /Vilanterol (VI)
100/25mcg inhaled
Drug: FF/VI
100/25
Experimental: Fluticasone Furoate/GSK573719
100/15.6-250mcg inhaled
Drug: FF/GSK573719
100/15.6
Drug: FF/GSK573719
100/31.25
Drug: FF/GSK573719
100/62.5
Drug: FF/GSK573719
100/125
Drug: FF/GSK573719
100/250

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Outpatient
  • 18 years of age or older at Visit 1
  • Diagnosis of Asthma
  • Male or eligible Female
  • Pre-bronchodilator FEV1 of 40-80% of the predicted normal value at Visit 1
  • Demonstrated reversibility by ≥12% and ≥200mL of FEV1 within 40 minutes following albuterol at Visit 1
  • A need for regular controller therapy (i.e., inhaled corticosteroids alone or in combination with a long‐acting beta‐agonist, or leukotriene modifier etc.,) for a minimum of 8 weeks prior to Visit 1.

Exclusion Criteria:

  • History of Life threatening asthma
  • Respiratory infection not resolved
  • Asthma exacerbation
  • Concurrent respiratory disease
  • Current Smokers
  • Other diseases that are uncontrolled disease or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study
  • A positive Hepatitis B surface antigen or positive Hepatitis C antibody and/or HIV
  • Visual clinical evidence of oropharyngeal candidiasis
  • Drug or milk protein allergies
  • Concomitant medications affecting course of asthma
  • Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
  • Previous use of GSK573719
  • Any disease preventing use of anticholinergics
  • Any condition that impairs compliance with study protocol including visit schedule and completion of daily diaries
  • Any subject with a history of alcohol or substance abuse
  • Any affiliation with Investigator's site
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01573624

Locations
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63141
United States, Oregon
GSK Investigational Site
Medford, Oregon, United States, 97504
United States, South Carolina
GSK Investigational Site
Orangeburg, South Carolina, United States, 29118
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Argentina
GSK Investigational Site
Buenos Aires, Argentina, C1424BSF
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina, C1425BEN
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
GSK Investigational Site
Mendoza, Argentina, M5500CCG
GSK Investigational Site
San Miguel de Tucumán, Argentina, 4000
GSK Investigational Site
Tucumán, Argentina, T4000DGF
Chile
GSK Investigational Site
Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7500551
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7500800
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 8880465
GSK Investigational Site
Talca, Región Metro De Santiago, Chile, 3460001
GSK Investigational Site
Valparaiso, Valparaíso, Chile, 2341131
GSK Investigational Site
Santiago, Chile, 8380453
Russian Federation
GSK Investigational Site
Barnaul, Russian Federation, 656038
GSK Investigational Site
Kazan, Russian Federation, 420015
GSK Investigational Site
Klin, Russian Federation, 141600
GSK Investigational Site
Moscow, Russian Federation, 115 280
GSK Investigational Site
Moscow, Russian Federation, 123367
GSK Investigational Site
Saint-Petersburg, Russian Federation, 194354
GSK Investigational Site
St. Petersburg, Russian Federation, 194356
GSK Investigational Site
Tomsk, Russian Federation, 634001
GSK Investigational Site
Tomsk, Russian Federation, 634055
GSK Investigational Site
Ufa, Russian Federation, 450071
GSK Investigational Site
Yaroslavl, Russian Federation, 150003
Thailand
GSK Investigational Site
Bangkok, Thailand, 10330
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Khon Kaen, Thailand, 40002
GSK Investigational Site
Nonthaburi, Thailand, 11000
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 115938
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01573624     History of Changes
Other Study ID Numbers: 115938
Study First Received: April 5, 2012
Results First Received: May 18, 2017
Last Updated: July 14, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

Keywords provided by GlaxoSmithKline:
Fluticasone Furoate
Vilanterol
Adults
GSK573719
Asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on September 20, 2017