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

NCT01573624 | Completed Phase 2 Results

• 1 other identifier: 115938
• Study Type: interventional
• Target: 421
• Locations: 5 countries
• Sites: 32

Brief Summary

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.

Conditions

Asthma

Keywords

Fluticasone Furoate; Vilanterol; Adults; GSK573719; Asthma

Outcome Measures

Primary Outcomes (3)

• Model Predicted Change From Baseline Trough Force Expiratory Volume in 1 Second (FEV1)

  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.

  Baseline (Day 1) and Day 15 of each treatment period

• 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

  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.

  Baseline (Day 1) and Day 15 of each treatment period

• Mean Change From Baseline in Trough FEV1 on Day 15 of Each of the 3 Treatment Periods

  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.

  Baseline (Day 1) and Day 15 of each treatment period

Secondary Outcomes (3)

• Mean Change From Baseline in Daily Morning (Pre-dose and Pre-rescue Bronchodilator) Peak Expiratory Flow (PEF) of Each Treatment Period

  Baseline (Week 0) and last 7 days of each treatment period

• Mean Change From Baseline in Daily Evening (Pre-dose and Pre-rescue Bronchodilator) PEF of Each Treatment Period

  Baseline (Week 0) and last 7 days of each treatment period

• Mean Change From Baseline in Rescue Albuterol/Salbutamol Use of Each Treatment Period.

  Baseline (Week 0) and last 7 days of each treatment period

Study Arms (3)

Fluticasone Furoate (FF)

ACTIVE COMPARATOR

100mcg, inhaled

Drug: FF

Fluticasone Furoate /Vilanterol (VI)

ACTIVE COMPARATOR

100/25mcg inhaled

Drug: FF/VI

Fluticasone Furoate/GSK573719

EXPERIMENTAL

100/15.6-250mcg inhaled

Drug: FF/GSK573719

Interventions

FF/GSK573719 DRUG

100/15.6

Fluticasone Furoate/GSK573719

FF DRUG

100

Fluticasone Furoate (FF)

FF/VI DRUG

100/25

Fluticasone Furoate /Vilanterol (VI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (32)

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Orangeburg, South Carolina, 29118, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Buenos Aires, C1424BSF, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425BEN, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

Mendoza, M5500CCG, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, T4000DGF, Argentina

Location

GSK Investigational Site

Valparaíso, Región de Valparaíso, 2341131, Chile

Location

GSK Investigational Site

Puente Alto - Santiago, Región Metro de Santiago, 8207257, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500551, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500800, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 8880465, Chile

Location

GSK Investigational Site

Talca, Región Metro de Santiago, 3460001, Chile

Location

GSK Investigational Site

Santiago, 8380453, Chile

Location

GSK Investigational Site

Barnaul, 656038, Russia

Location

GSK Investigational Site

Kazan', 420015, Russia

Location

GSK Investigational Site

Klin, 141600, Russia

Location

GSK Investigational Site

Moscow, 115 280, Russia

Location

GSK Investigational Site

Moscow, 123367, Russia

Location

GSK Investigational Site

Saint Petersburg, 194354, Russia

Location

GSK Investigational Site

Saint Petersburg, 194356, Russia

Location

GSK Investigational Site

Tomsk, 634001, Russia

Location

GSK Investigational Site

Tomsk, 634055, Russia

Location

GSK Investigational Site

Ufa, 450071, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Bangkok, 10400, Thailand

Location

GSK Investigational Site

Khon Kaen, 40002, Thailand

Location

GSK Investigational Site

Nonthaburi, 11000, Thailand

Location

Related Publications (1)

• Lee LA, Yang S, Kerwin E, Trivedi R, Edwards LD, Pascoe S. The effect of fluticasone furoate/umeclidinium in adult patients with asthma: a randomized, dose-ranging study. Respir Med. 2015 Jan;109(1):54-62. doi: 10.1016/j.rmed.2014.09.012. Epub 2014 Oct 2.

  PMID: 25452139 DERIVED

Related 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.

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2012
• First Posted: April 9, 2012
• Study Start: April 3, 2012
• Primary Completion: February 4, 2013
• Study Completion: February 4, 2013
• Last Updated: October 6, 2017
• Results First Posted: August 15, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

AR (6); US (4); RU (11); CL (7); TH (4)