Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Combination of GSK573719 and GW642444 in Subjects With COPD

The study will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of the combination of inhaled GSK573719 and GW64244 compared to placebo, in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: 500mcg/25mcg once daily; Drug: Placebo once daily

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and tolerability of the combination of GSK573719 (500mcg) Inhalation Powder and GW642444 (25mcg) Inhalation Powder administered once-daily via a novel dry powder inhaler (Novel DPI) over 28 days in subjects with COPD

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Chester, South Carolina, United States, 29706
      • GSK Investigational Site
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Greenwood, South Carolina, United States, 29646
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (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 or more 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 80% or less of predicted normal

Exclusion Criteria:

• Current diagnosis of asthma
• Other significant respiratory disorders besides COPD, including alpha-1 deficiency
• Previous lung resection surgery
• Significant abnormalities in chest x-ray presentation
• Use of oral steroids, antibiotics or hospitalization for a COPD exacerbation within 3 motnhs prior screening
• Any significant disease that would put subject at risk through study participation
• BMI greater than 35
• Pacemaker
• Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or C)
• Cancer
• Allergy or hypersensitivity to anticholinergics or inhaler excipients
• Diseases that would contra-indicate 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 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
• Previous use of GSK573719 or GW642444

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo once daily; Inactive, excipients only
Experimental: GSK573719/GW642444	Drug: 500mcg/25mcg once daily; GSK573719/GW642444

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 28	Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/time curve (AUC), and then dividing the value by the time interval over which the AUC was calculated. The weighted mean pulse rate was calculated using the 0 to 6 hours post dose measurements at Day 28, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 28 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.	Baseline and Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 1 and Day 14	Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean pulse rate was calculated using the 0 to 6 hours post dose measurements on Day 1 and Day 14, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 1 or Day 14 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.	Baseline, Day 1, and Day 14
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28	Pulse rate is defined as the number of heartbeats in a minute (m). A maximum post-Baseline pulse rate was derived as the maximum value recorded at Days 1, 14 and 28. A minimum post-Baseline pulse rate was derived as the minimum value recorded at Days 1, 14 and 28. The maximum and minimum pulse rates were calculated using the 0 to 6 hours (h) post dose measurements on Days 1, 14 and 28, which included pre-dose, and post-dose 15 m, 45 m, 1.5 h, 3 h and 6 h. Maximum and minimum post-Baseline rate were calculated using the nominal 0-6 h post-dose records, and only records collected during the actual 0-7 h post-dose interval were used. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the maximum or minimum pulse rate minus the Baseline value. Analysis performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.	Baseline, Day 1, Day 14 and Day 28

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Feldman G, Walker RR, Brooks J, Mehta R, Crater G. 28-Day safety and tolerability of umeclidinium in combination with vilanterol in COPD: a randomized placebo-controlled trial. Pulm Pharmacol Ther. 2012 Dec;25(6):465-71. doi: 10.1016/j.pupt.2012.08.007. Epub 2012 Aug 31.

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: January 1, 2010
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 20, 2010

Study Registration Dates

• First Submitted: December 23, 2009
• First Submitted That Met QC Criteria: December 23, 2009
• First Posted (Estimate): December 25, 2009

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: COPD; pharmacokinetics; pharmacodynamics; Safety and tolerability; long-acting muscarinic receptor antagonist; long-acting beta2-receptor agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 113120

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. Individual Participant Data Set
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 113120
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register