Clinical trial NCT01573624: Evaluate the Safety, Efficacy and Dose Response of GSK573719 in Combination With Fluticasone Furoate in Subjects With Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Fluticasone Furoate
Vilanterol
Adults
GSK573719
Asthma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-04-09
Enrollment: 421
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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.


Eligibility 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

Primary outcomes:
measure: Model Predicted Change From Baseline Trough Force Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline (Day 1) and Day 15 of each treatment period
measure: 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
timeFrame: Baseline (Day 1) and Day 15 of each treatment period
measure: Mean Change From Baseline in Trough FEV1 on Day 15 of Each of the 3 Treatment Periods
timeFrame: Baseline (Day 1) and Day 15 of each treatment period
Secondary outcomes:
measure: Mean Change From Baseline in Daily Morning (Pre-dose and Pre-rescue Bronchodilator) Peak Expiratory Flow (PEF) of Each Treatment Period
timeFrame: Baseline (Week 0) and last 7 days of each treatment period
measure: Mean Change From Baseline in Daily Evening (Pre-dose and Pre-rescue Bronchodilator) PEF of Each Treatment Period
timeFrame: Baseline (Week 0) and last 7 days of each treatment period
measure: Mean Change From Baseline in Rescue Albuterol/Salbutamol Use of Each Treatment Period.
timeFrame: Baseline (Week 0) and last 7 days of each treatment period
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: San Miguel de Tucumán
country: Argentina
facility: GSK Investigational Site
city: Tucumán
country: Argentina
facility: GSK Investigational Site
city: Puente Alto - Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Talca
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Valparaiso
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Barnaul
country: Russian Federation
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Klin
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Ufa
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Nonthaburi
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.