A Randomized, Double Blind, Placebo Controlled, Incomplete Block, Crossover, Dose Ranging Study to Evaluate the Dose Response of GSK573719 Administered Once or Twice Daily Over 7 Days in Patients With Chronic Obstructive Pulmonary Disease (COPD)
AC4115321
1 other identifier
interventional
163
1 country
13
Brief Summary
The purpose of this study is to further characterize the dose response of GSK573719 at doses of 15.6 micrograms (mcg) to 125 mcg once daily in patients with chronic obstructive pulmonary disease (COPD). Treatment with doses of GSK573719 dosed twice daily will also be included to further evaluate dosing frequency. Treatment with tiotropium (18 mcg) once daily via the Handihaler will be included as an active control. A placebo treatment will be included in order to evaluate absolute treatment effect of the different doses of GSK573719.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2011
Shorter than P25 for phase_2
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 9, 2011
CompletedFirst Posted
Study publicly available on registry
June 13, 2011
CompletedStudy Start
First participant enrolled
July 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
October 27, 2011
CompletedResults Posted
Study results publicly available
February 11, 2014
CompletedNovember 8, 2017
October 1, 2017
3 months
June 9, 2011
December 19, 2013
October 9, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)
The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate trough FEV1dose response. The Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed separately and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. The fixed-effects parameters of the dose response model include Emax (the maximum predicted FEV1 response), ED50 (potency), and S0 (estimated Baseline FEV1). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Data for Emax and S0 are reported in this table. mITT=Modified Intent-to-Treat; par.=participants; BL=Baseline.
Day 7 and Day 8 of each treatment period (up to Study Day 50)
Final Dose-response Model for Trough FEV1 for ED50 (Potency) Parameter
The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate dose response. Both a Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. ED50 is defined as the potency and is the dose that yields 50% of Emax (maximum predicted FEV1 response). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Day 7 and Day 8 of each treatment period (up to Study Day 50)
Final Dose-response Model Parameter β-FEV1MB-S0 for Trough FEV1
The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate dose response. Both a Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. β-FEV1MB-S0 is defined as the covariate (Baseline trough FEV1) effect on the mean Baseline trough FEV1 estimate (S0). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Day 7 and Day 8 of each treatment period (up to Study Day 50)
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 8 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 8 is defined as the value obtained 24 hours after the morning dose administered on Day 7. Analysis was performed using a mixed model with covariates of mean Baseline, period Baseline, treatment, and period as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each particiapant. Change from Baseline for each treatment period is the trough FEV1 at Day 8 minus the Baseline value for that treatment period.
Baseline and Day 8 of each treatment period (up to Study Day 50)
Secondary Outcomes (2)
Change From Baseline (BL) in Serial FEV1 Over Time on Day 7 of Each Treatment Period
Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours After the Morning Dosing on Day 7 of Each Treatment Period
Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
Study Arms (3)
Tiotropium
ACTIVE COMPARATOR18 mcg, inhaled long acting muscarinic antagonist
GSK573719
EXPERIMENTALinhaled medication
Placebo
PLACEBO COMPARATORinactive/excipients only
Interventions
Eligibility Criteria
You may qualify if:
- Outpatient
- A signed and dated written informed consent prior to study participation.
- Male or female adults.
- to 80 years of age at Visit 1
- Diagnosis of COPD
- Current or former cigarette smokers with a history of cigarette smoking of greater than or equal to 10 pack-years
- Post-albuterol forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC)\<0.70 and post albuterol FEV1 of greater than or equal to 35% and less than or equal to 70% of predicted normal values
You may not qualify if:
- Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- A current diagnosis of asthma
- Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer
- Other significant respiratory conditions in addition to COPD
- Other diseases that are uncontrolled including cancer in remission for less than 5 years
- Chest x-ray or CT scan with clinically significant abnormalities not believed to be due to the presence of COPD
- Hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate
- A medical condition that contraindicates study participation or use of an inhaled anticholinergic
- Hospitalization for COPD or pneumonia within 12 weeks of Visit 1
- Any previous lung resection surgery
- A body mass index (BMI) value of \>35 kilogram (kg)/meter squared (m2)
- An abnormal and significant electrocardiogram finding at Visit 1
- Significantly abnormal finding from clinical chemistry or haematology tests at Visit 1.
- A positive Hepatitis B surface antigen or positive Hepatitis C antibody
- Medically unable to withhold albuterol (salbutamol) for the 6 hour period prior to study visits
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (13)
GSK Investigational Site
Costa Mesa, California, 92626, United States
GSK Investigational Site
Atlanta, Georgia, 30342, United States
GSK Investigational Site
Duluth, Georgia, 30096, United States
GSK Investigational Site
Edina, Minnesota, 55438, United States
GSK Investigational Site
Charlotte, North Carolina, 28207, United States
GSK Investigational Site
Raleigh, North Carolina, 27607, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73103, United States
GSK Investigational Site
Easley, South Carolina, 29640, United States
GSK Investigational Site
Gaffney, South Carolina, 29340, United States
GSK Investigational Site
Greenville, South Carolina, 29615, United States
GSK Investigational Site
Orangeburg, South Carolina, 29118, United States
GSK Investigational Site
Spartanburg, South Carolina, 29303, United States
GSK Investigational Site
Union, South Carolina, 29379, United States
Related Publications (1)
Church A, Beerahee M, Brooks J, Mehta R, Shah P. Dose response of umeclidinium administered once or twice daily in patients with COPD: a randomised cross-over study. BMC Pulm Med. 2014 Jan 6;14:2. doi: 10.1186/1471-2466-14-2.
PMID: 24393134DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
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
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 9, 2011
First Posted
June 13, 2011
Study Start
July 1, 2011
Primary Completion
October 1, 2011
Study Completion
October 27, 2011
Last Updated
November 8, 2017
Results First Posted
February 11, 2014
Record last verified: 2017-10
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.