Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 4-week Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Inhaled Doses of the Combination of GSK233705 and GW642444 Administered Once-daily in Subjects With COPD

The purpose of this study is the evaluate the safety and tolerability of repeat dosing of the combination of inhaled GSK233705 and GW642444 administered once-daily in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: GSK233705/GW642444

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • GSK Investigational Site
  • Maine
    • Biddeford, Maine, United States, 04005
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • New Jersey
    • Summit, New Jersey, United States, 07091
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16508
      • GSK Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37601
      • GSK Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • 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:

• male and females 40 to 80 years of age (inclusive)
• COPD diagnosis
• Current or previous smokers with a cigarette smoking history of at least 10 pack-
• Post-albuterol FEV1/FVC of 0.70 or less
• Post-albuterol FEV1 of 35% to 80% (inclusive)

Exclusion Criteria:

• Pregnant or lactating females
• current diagnosis of asthma
• respiratory disorders other than COPD
• clinically significant cardiovascular, neurological, psychiatric, renal, immunological, endocrine, or hematological abnormalities that are uncontrolled
• clinically significant sleep apnea
• previous lung resection surgery
• clinically significant abnormalities confirmed by chest x-ray that are not related to COPD
• hospitalization for COPD within 3 months of screening
• use of antibiotics for lower respiratory tract infection within 6 months of screening
• abnormal and clinically significant 12-lead ECG findings
• current malignancy in remission for less that 5 years
• medical conditions that would contraindicate the use of anticholinergics
• positive hepatitis B or C test
• history of alcohol or drug abuse
• unable to withhold albuterol for 6 or more hours
• use of long term oxygen therapy
• conditions that would limit the validity of informed consent
• use of GW642444 or GSK233705 in previous studies
• use of an investigation drug with 30 days of screening
• use of inhaled corticosteroids (ICS) at a dose greater than 1000mcg of fluticasone propionate or equivalent
• hypersensitivity to beta-agonists
• concurrent use of long-acting beta-agonists (LABA) or long-acting muscaring antagonists, LABA/ICS combination products, cytochrome p450 inhibitors, oral or depot corticosteroids, theophyllines, oral beta agonists, oral leukotrine modulators, inhaled short acting anticholinergics.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: GSK233705/GW642444; The combination of the long-acting muscarinic antagonist GSK233705 and the long acting beta agonist GW642444 in a single inhaler.
Placebo Comparator: Arm 2	Drug: Placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28.	Baseline was the most recent result taken on or before pre-dose (Day 1). The analysis was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded. Change from Baseline was calculated as (Change from Baseline = Assessment value - Baseline value).	Baseline (Pre-dose, Day 1) and Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.	On-treatment; from treatment start until one day after treatment stop (Up to Day 29)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• GSK has submitted manuscripts of these study results to peer-reviewed scientific journals which were not accepted for publication. GSK is providing the attached study results summary with a conclusion.

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): November 13, 2008
• Primary Completion (Actual): February 12, 2009
• Study Completion (Actual): February 12, 2009

Study Registration Dates

• First Submitted: September 8, 2008
• First Submitted That Met QC Criteria: September 8, 2008
• First Posted (Estimate): September 9, 2008

Study Record Updates

• Last Update Posted (Actual): September 1, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: COPD; Chronic Bronchitis; Emphysema; Chronic Obstructive Pulmonary Disease (COPD); bronchodilator; long-acting beta agonist; long acting muscarinic antagonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: DB1111581

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: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: DB1111581
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register