28-day Repeat Dose Study of GSK573719

A Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK573719 Delivered Once-daily Over 28 Days in Subjects With COPD

The study will evaluate the efficacy, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: GSK573719 125mcg; Drug: GSK573719 250mcg; Drug: GSK573719 500mcg

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 3 doses of GSK573719 administered once-daily over 28 days in subjects with COPD.

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 13419
    • GSK Investigational Site
  • Tallinn, Estonia, 13619
    • GSK Investigational Site
  • Tallinn, Estonia, 10138
    • GSK Investigational Site
  • Tartu, Estonia, 51014
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 14057
    • GSK Investigational Site
  • Berlin, Germany, 13125
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Hamburg, Germany, 20253
    • GSK Investigational Site
  • Hessen
    • Wiesbaden, Hessen, Germany, 65187
      • GSK Investigational Site
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
      • GSK Investigational Site
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany, 22927
      • GSK Investigational Site
• Poland
  • Bialystok, Poland
    • GSK Investigational Site
  • Bialystok, Poland, 15-027
    • GSK Investigational Site
  • Gidle, Poland, 97-540
    • GSK Investigational Site
  • Krakow, Poland, 31-023
    • GSK Investigational Site
  • Lublin, Poland, 20-637
    • GSK Investigational Site
• United States
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A signed and dated written informed consent prior to study participation
• Males or females of non-childbearing potential
• 40 to 80 years of age
• COPD diagnosis
• 10 pack-years history or greater of cigarette smoking
• Post-bronchodilator FEV1/FVC ratio of 0.70 or less
• Post-bronchodilator FEV1 of 25 to 70% of predicted normal

Exclusion Criteria:

• Asthma
• Other significant respiratory disorders besides COPD, including alpha-1 deficiency
• Previous lung resection surgery
• Chest X-ray or CP scan showing clinically significant abnormalities not due to COPD
• Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of screening
• Hospitalization for COPD or pneumonia within 3 months of screening
• Any significant disease that would put subject at risk through study participation
• BMI greater than 35
• Pacemaker
• Significantly abnormal ECG or clinical lab finding (including Hepatitis B or C)
• Cancer
• Allergy or hypersensitivity to anticholinergics or inhaler excipients
• Diseases that would contraindicate the use of anticholinergics
• Use of oral corticosteroids within 6 weeks of screening
• Use of long-acting beta-agonists within 48 hours of screening
• Use of tiotropium within 14 days of screening
• Use of theophyllines or anti-leukotrienes within 48 hours of screening
• Use of short-acting bronchodilators within 4 to 6 hours of screening
• Use of investigational medicines within 30 days of screening
• Use of high dose inhaled corticosteroids
• Use of long-term oxygen therapy, CPAP or NIPPV
• Participation in acute phase of pulmonary rehabilitation program
• History of alcohol or drug abuse within 2 years prior to screening
• History of psychiatric disease limiting validity of consent
• Affiliation with the investigative site
• Previous use of GSK573719

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GSK573719 125mcg; 125mcg once-daily via novel dry powder inhaler	Drug: GSK573719 125mcg; 125mcg once-daily
EXPERIMENTAL: GSK573719 250mcg; 250mcg once-daily via novel dry powder inhaler	Drug: GSK573719 250mcg; 250mcg once-daily
EXPERIMENTAL: GSK573719 500mcg; 500mcg once-daily via novel dry powder inhaler	Drug: GSK573719 500mcg; 500mcg once-daily
PLACEBO_COMPARATOR: Placebo; once-daily via novel dry powder inhaler	Drug: Placebo; once-daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 29	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 29 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 28. Baseline is defined as the mean of the FEV1 values obtained at 30 minutes and immediately pre-dose on Day 1. Change from Baseline is defined as the difference between trough on Day 29 and Baseline. Analysis was performed using a repeated measures model with covariates of Baseline (BL), country, sex, age, treatment, smoking status, day, day by Baseline interaction, and day by treatment interaction.	Baseline and Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at Day 1 and Day 28	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean FEV1 was derived by calculating the area under the FEV1/time curve (AUC), and then dividing the value by the time interval over which the AUC was calculated. The weighted mean was calculated using the 0-6 hour post-dose measurements at Days 1 and 28, which included pre-dose (30 minutes prior to dosing on Day 1, or 24 hours after the previous day's dose on Day 28), and post-dose at 15 minutes, 30 minutes, 1 hour, 3 hours, and 6 hours. Baseline is defined as the mean of the FEV1 values obtained at 30 minutes and immediately pre-dose on Day 1. Change from Baseline is defined as the difference between weighted mean at Days 1 and 28 and Baseline. Analysis was performed using a repeated measures model with covariates of Baseline, country, sex, age, treatment, smoking status, day, day by Baseline interaction, and day by treatment interaction.	Baseline, Day 1, and Day 28
Change From Baseline in Serial FEV1 Over 24 Hours After Dosing at Day 1 and Day 28	Serial spirometry assessments were conducted on Day 1 and Day 28 over the course of 24 hours and were obtained 0 (Day 28 only), 1, 3, 6, 23, and 24 hours after dosing. Baseline is defined as the mean of the FEV1 values obtained at 30 minutes and immediately pre-dose on Day 1. Change from Baseline is defined as the difference between FEV1 on Days 1 and 28 and Baseline.	Baseline, Day 1, and Day 28

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Decramer M, Maltais F, Feldman G, Brooks J, Harris S, Mehta R, Crater G. Bronchodilation of umeclidinium, a new long-acting muscarinic antagonist, in COPD patients. Respir Physiol Neurobiol. 2013 Jan 15;185(2):393-9. doi: 10.1016/j.resp.2012.08.022. Epub 2012 Sep 28.

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 (ACTUAL): December 15, 2009
• Primary Completion (ACTUAL): July 4, 2010
• Study Completion (ACTUAL): July 4, 2010

Study Registration Dates

• First Submitted: December 10, 2009
• First Submitted That Met QC Criteria: December 10, 2009
• First Posted (ESTIMATE): December 14, 2009

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2018
• Last Update Submitted That Met QC Criteria: February 8, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: COPD; Chronic Bronchitis; Emphysema; Anticholinergic; Long-acting muscarinic antagonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 113589

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. Study Protocol
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 113589
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register