GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00950807
First received: July 30, 2009
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium
Drug: Placebo
Drug: GSK573179
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of GSK573719 Administered Once- and Twice-Daily in Subjects With COPD

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period [ Time Frame: Baseline and Day 15 of each treatment period (up to Study Day 71) ] [ Designated as safety issue: No ]
    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 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis were 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 participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.


Secondary Outcome Measures:
  • Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period [ Time Frame: Baseline and Day 14 of each treatment period (TP; up to Study Day 70) ] [ Designated as safety issue: No ]
    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) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean FEV1 was calculated using 0-24 hour (h) post-dose measurements at Day 14 of each treatment period, which included pre-dose and post-dose 1, 3, 6, 9, 12, 13, 15, 18, 21 and 24 hours. Analysis performed using a mixed model with covariates mean BL, period BL, treatment and period as fixed effects and participant as a random effect. BL is the FEV1 value recorded pre-dose on Day 1 of each TP; mean BL is the mean of the BLs for each participant and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.

  • Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period [ Time Frame: Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70) ] [ Designated as safety issue: No ]
    Serial FEV1 for OQ dosing is recorded at the pre-AM dose (time 0 h) and at 1, 3, 6, 9, 12,13, 15, 18, 21, 24 and 28 hs after the AM dose on D 14. For BID dosing, the 12 h AM dose corresponds to the pre-PM dose, 13 h AM dose corresponds to the 1 h PM dose, 15 h AM dose corresponds to the 3 h PM dose, 18 h AM corresponds to the 6 h PM dose, 21 h AM dose corresponds to 9 h PM dose, 24 h AM dose corresponds to the 12 h PM dose and 28 h AM dose corresponds to the 16 h PM dose in the table. Analysis performed using a mixed model with covariates of mean BL, period BL, trt, period, time, time by period BL interaction, time by mean BL interaction and time by trt interaction as fixed effects and par. as a random effect. BL is the FEV1 value recorded pre-dose on D 1 of each TP; mean BL is the mean of the BLs for each par. and period BL is the difference between the BL and the mean BL in each TP for each par. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.


Enrollment: 176
Study Start Date: September 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Inactive/ excipients only
Active Comparator: Tiotropium
Tiotropium
Drug: Tiotropium
long-acting muscarinic receptor antagonist; 18mcg once-daily
Experimental: Arm 1
GSK573719 1000mcg once daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 2
GSK573719 500mcg once daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 3
GSK573719 250mcg once daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 4
GSK573719 125mcg once daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 5
GSK573719 62.5 mcg once daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 6
GSK573719 250mcg twice daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 7
GSK573719 125mcg twice daily
Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 8
GSK573719 62.5mcg twice daily
Drug: GSK573179
GSK573179 investigational drug

Detailed Description:

This is multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, incomplete block design study to evaluation of 5 doses of GSK573719 administered once-daily and 3 doses of GSK573719 administered twice-daily over 14 days in subjects with COPD and will include tiotropium as an open-label active control. The pharmacokinetic profile of GSK573719 will also be evaluated.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 35 to 70% of predicted normal

Exclusion Criteria:

  • Asthma
  • Other significant respiratory disorders besides COPD, including alpha-1 deficiency
  • Previous lung resection surgery
  • 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, 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 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
  • Previous use of GSK573719
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00950807

Locations
United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85013
United States, California
GSK Investigational Site
San Diego, California, United States, 92117
GSK Investigational Site
Upland, California, United States, 91786
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45231
United States, South Carolina
GSK Investigational Site
Easley, South Carolina, United States, 29640
GSK Investigational Site
Gaffney, South Carolina, United States, 29340
GSK Investigational Site
Greenville, South Carolina, United States, 29615
GSK Investigational Site
Seneca, South Carolina, United States, 29678
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
GSK Investigational Site
Union, South Carolina, United States, 29379
Germany
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
GSK Investigational Site
Wiesbaden, Hessen, Germany, 65187
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
GSK Investigational Site
Berlin, Germany, 10787
GSK Investigational Site
Berlin, Germany, 13125
GSK Investigational Site
Hamburg, Germany, 20253
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00950807     History of Changes
Other Study ID Numbers: 113073
Study First Received: July 30, 2009
Results First Received: January 16, 2014
Last Updated: January 16, 2014
Health Authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
United States: Food and Drug Administration
Europe: European Medicines Agency

Keywords provided by GlaxoSmithKline:
Dose ranging
Chronic Bronchitis
Long-acting muscarinic antagonist
cross-over
COPD
Emphysema
Chronic Obstructive Pulmonary Disease (COPD)
anticholinergic

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Muscarinic Antagonists
Tiotropium
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014