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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00749411
First received: September 8, 2008
Last updated: January 13, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Placebo
Drug: GSK233705/GW642444
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from Baseline (Day 1) in weighted mean pulse rate over (0-4hours) at Day 28. [ Time Frame: Day 1 and 28 ]
    Least Square Mean Change analyses change from baseline. Baseline is the most recent result taken on or before pre-dose Day 1. The analysis of the primary endpoint was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded on nominal clinic Days 1, 14 and 28.


Secondary Outcome Measures:
  • Change from baseline in weighted mean systolic blood pressure over 0-4 hours post-dose on Days 1, 14, and 28 [ Time Frame: Days 1, 14 and 28 ]
    The weighted mean systolic blood pressure is denoted by values of Least Square Mean Change to show the change from baseline (in systolic blood pressure) on day 14 and 28.

  • Change from baseline in maximum systolic blood pressure over 0-4 hours post-dose on Days 1, 14, and 28 [ Time Frame: Days 1,14 and 28 ]
    The baseline is the most recent result (maximum systolic blood pressure) taken on or before pre-dose 1, it is denoted by Least Square Mean Change values.

  • Change fro baseline in weighted mean diastolic blood pressure over 0-4 hours post-dose on Days 1, 14, and 28 [ Time Frame: Days 1, 14 and 28 ]
    The weighted mean diastolic blood pressure was analyzed using a Repeated Measures Model. Values of Least Square Mean Change denote the change from baseline on day 14 and 28.

  • Change from baseline in maximum diastolic blood pressure over 0-4 hours post-dose on Days 1, 14, and 28 [ Time Frame: Days 1,14 and 28 ]
    The maximum diastolic blood pressure was analyzed using a Repeated Measures Model. Values of Least Square Mean Change denote the change from baseline on day 14 and 28.

  • Change from baseline in weighted mean plasma glucose over 0-4 hrs post-dose on Days 1, 14 and 28 [ Time Frame: Days 1, 14 and 28 ]
    The weighted mean plasma glucose was analyzed using a Repeated Measures Model. Values of Least Square Mean Change denote the change from baseline on day 14 and 28.

  • Change from baseline in maximum plasma glucose over 0-4 hrs post-dose on Days 1, 14 and 28 [ Time Frame: Day 1,14 and 28 ]
    The maximum plasma glucose was analyzed using a Repeated Measures Model. Values of Least Square Mean Change denote the change from baseline on day 14 and 28.

  • Change from baseline in weighted mean serum potassium over 0-4 hrs post-dose on Days 1, 14, and 28 [ Time Frame: Days 1, 14 and 28 ]
    The weighted mean serum potassium was analyzed using a Repeated Measures Model. Values of Least Square Mean Change denote the change from baseline on day 14 and 28.

  • Change from baseline in maximum serum potassium over 0-4 hrs post-dose on Days 1, 14, and 28 [ Time Frame: Day 1, 14 and 28 ]
    The maximum serum potassium was analyzed using a Repeated Measures Model. Values of Least Square Mean Change denote the change from baseline on day 14 and 28.

  • Weighted mean QTc interval corrected by Fridericia's method (F) over 0-4 hrs post-dose on Days 1, 14 and 28. [ Time Frame: Days 1, 14 and 28 ]
    Participants were monitored for 28 days. The QTcF values were taken on day 14 and 28 to analyze the change from baseline (Day 1). There was no statistical evidence of a difference at Day 1, 14 and 28 in weighted mean QTcF

  • Weighted mean QTc interval corrected by Bazett's method (B) over 0-4 hrs post-dose on Days 1, 14 and 28. [ Time Frame: Days 1, 14 and 28 ]
    Participants were monitored for 28 days. The QTcB values were taken on day 14 and 28 to analyze the change from baseline (Day 1). There was no statistical evidence of a difference at Day 1, 14 and 28 in weighted mean QTcB

  • Maximum QTc interval corrected by Fridericia's method (F) over 0-4 hrs post-dose on Days 1, 14 and 28. [ Time Frame: Day 1, 14 and 28 ]
    Participants were monitored for 28 days. The QTcF values were taken on day 14 and 28 to analyze the change from baseline (Day 1). There was no statistical evidence of a difference at Day 1, 14 and 28 in maximum QTcF

  • Maximum QTc interval corrected by Bazett's method (B) over 0-4 hrs post-dose on Days 1, 14 and 28. [ Time Frame: Days 1, 14 and 28 ]
    Participants were monitored for 28 days. The QTcB values were taken on day 14 and 28 to analyze the change from baseline (Day 1). There was no statistical evidence of a difference at Day 1, 14 and 28 in maximum QTcB

  • Premature ventricular beats, premature supraventricular beats and ventricular runs derived from 3-lead 24-hour Holter ECG monitoring at screening and Day 28 [ Time Frame: Screening, Day 28 ]
    The premature ventricular (PVE) and supraventricular ectopic (SPVE) per participant were recorded on screening and day 28. No abnormal ventricular runs were recorded.

  • Change from baseline from post dose Trough Force Expiratory Volume 1 (FEV1) on Days 2, 14, 28 and 29 [ Time Frame: Days 2, 14, 28 and 29 ]
    Treatment with GSK233705/GW642444 resulted in an increase in mean serial Forced Expiratory Volume 1 (FEV1) values, they were obtained at 30 minutes and 1 hour post-dose using spirometer on visit 2,5 and 6.

  • Post-dose FEV1 (at 30 and 60 min) on Days 1, 14 and 28 [ Time Frame: Days 1, 14 and 28 ]
    Post dose FEV1 was measured using spirometer at visit 2, 5 and 6. Participant receiving treatment of GSK233705+GW642444 resulted in an increase in mean serial FEV1 values obtained 30 minutes and 1 hour post-dose, while the participants receiving placebo have shown progressive decrease in FEV1 values from baseline.

  • Number of participants with adverse events (AEs) and serious adverse events (SAEs) over period [ Time Frame: Up to 37 days ]
    One serious adverse events (SAE) of chronic obstructive pulmonary disease is reported pre-treatment. The participant could not be classified under an arm since the adverse event (AE) occurred before treatment. Only on treatment adverse event are presented.


Enrollment: 61
Study Start Date: November 2008
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749411

Locations
United States, Alabama
GSK Investigational Site
Mobile, Alabama, United States, 36608
United States, Colorado
GSK Investigational Site
Wheat Ridge, Colorado, United States, 80033
United States, Maine
GSK Investigational Site
Biddeford, Maine, United States, 04005
United States, Missouri
GSK Investigational Site
St. Louis, Missouri, United States, 63141
United States, New Jersey
GSK Investigational Site
Summit, New Jersey, United States, 07091
United States, Oregon
GSK Investigational Site
Medford, Oregon, United States, 97504
United States, Pennsylvania
GSK Investigational Site
Erie, Pennsylvania, United States, 16508
United States, South Carolina
GSK Investigational Site
Greenville, South Carolina, United States, 29615
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
GSK Investigational Site
Johnson City, Tennessee, United States, 37601
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
United States, Washington
GSK Investigational Site
Spokane, Washington, United States, 99204
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
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.

Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: DB1111581
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00749411     History of Changes
Obsolete Identifiers: NCT00843206
Other Study ID Numbers: DB1111581 
Study First Received: September 8, 2008
Last Updated: January 13, 2017
Individual Participant Data  
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
COPD
long-acting beta agonist
Emphysema
Chronic Bronchitis
Chronic Obstructive Pulmonary Disease (COPD)
bronchodilator
long acting muscarinic antagonist

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on January 19, 2017