Evaluate the Efficacy and Safety of GSK573719 Delivered Via a Novel Dry Powder Inhaler in Subjects With COPD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01387230
First received: June 30, 2011
Last updated: December 19, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to assess if 12 weeks' treatment with GSK573719 Inhalation Powder is safe and effective compared with placebo or no active drug intake, when administered once-daily in subjects with Chronic Obstructive Pulmonary Disease (COPD).


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GSK573719
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of GSK573719 Delivered Once-Daily Via a Novel Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 [ Time Frame: Baseline and Day 85 ] [ 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 measurements were taken electronically by spirometry on Days 2, 14, 28, 56, 84, and 85. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions.


Secondary Outcome Measures:
  • Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) [ Time Frame: Baseline and Days 1, 28 and 84 ] [ 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 WM 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 WM was calculated at Days 1, 28, and Day 84 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 1 hour, 3 hours, and 6 hours. Change from Baseline was the WM minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions.

  • Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) [ Time Frame: Baseline, Day 1 and Day 84 ] [ Designated as safety issue: No ]
    Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 measurements of interest for Day 1 were collected at 1, 3, 6, 23 and 24 hours post-dose on Day 1 and for Day 84, the measures were pre-dose (24 hours post-dose of Day 83 morning dose but prior to Day 84's dose) and 1, 3, 6, 23 and 24 hours post dose on Day 84. Baseline is the mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis performed separately by Visit/Day using a repeated measures model with covariates of treatment, Baseline, smoking status, center group, time, time by Baseline and time by treatment interactions.


Enrollment: 206
Study Start Date: July 2011
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK573719
active drug
Drug: GSK573719
62.5 mcg
Other Name: GSK573719
Drug: GSK573719
125mcg
Other Name: GSK573719
Placebo Comparator: Placebo
no active drug
Other: Placebo
Placebo
Other Name: Placebo

Detailed Description:

Inhaled bronchodilators, such as beta 2 agonists and anticholinergics, and inhaled corticosteroids are the mainstays of therapy in patients diagnosed with COPD. Anticholinergic bronchodilators or long acting muscarinic receptor antagonists function by blocking endogenous airway smooth muscle cholinergic tone. Treatment with anticholinergics has been shown to significantly improve forced expiratory volume in 1 second (FEV1), resting and dynamic lung hyperinflation, symptoms, and exercise capacity in patients with COPD. Currently tiotropium is the only approved long acting muscarinic antagonist available for treatment of COPD.This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder of 2 doses when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD. There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. There will be 8 clinic visits during three of which serial spirometry will be performed . The total duration of subject participation in the study will be approximately 14 weeks.

This is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder 62.5 mcg and 125 mcg when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD.

Eligible subjects will be randomized 1:1:1 to receive either of the two doses of GSK573719 Inhalation Powder doses or placebo for 12 weeks.

There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. Clinic visits will be at Screening, Randomization (Visit 2), Day 3 and Weeks 2, 4, 8, and 12, and 1 day after the Week 12 visit (Visits 1 to 8, respectively). A safety follow-up assessment will be conducted by telephone approximately 7 days after the end of the study treatment (FU Phone Contact). The total duration of subject participation, including the follow-up period will be approximately 14 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the run-in and treatment periods.

Pre-dose spirometry will be conducted at each clinic visit. Six hour post-dose serial spirometry will be conducted at Visit 2 and at Visits 5 and 7. All subjects will be provided with a paper diary for completion everyday throughout the run-in period and 12-week treatment period. Subjects will use the diary to record their daily use of supplemental albuterol/salbutamol and to record any medical problems experienced and any medications used.

At Visit 2 the Baseline Dyspnea Index (BDI) will be administered. The Transition Dyspnea Index (TDI) will be administered at Visits 5, 6, and 7.

Disease specific health status will be evaluated using the St. George's Respiratory Questionnaire (SGRQ) at Visit 2 and Visits 5, 6 and 7. Vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and blood biochemistry) including pharmacokinetic samples will be obtained at selected clinic visits.

Approximately 198 subjects will be randomized to ensure at least 168 subjects complete the treatment period.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of COPD
  • 10 pack-year or greater history of cigarette smoking
  • Post-bronchodilator FEV1/FVC of <0.7
  • Predicted FEV1 of 70% of normal or less
  • Modified Medical Research Council (mMRC) dyspnea score of 2 or greater

Exclusion Criteria:

  • Women who are pregnant, lactating, or planning to become pregnant
  • Respiratory disorders other than COPD, including a current diagnosis of asthma
  • Clinically significant non-respiratory diseases or abnormalities that are not adequately controlled
  • Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, or the excipients of magnesium stereate or lactose used in the inhaler delivery device
  • Hospitalization for COPD or pneumonia within 12 weeks prior to screening
  • Lung volume reduction surgery within 12 weeks prior to screening
  • Abnormal and clinically significant ECG findings at screening
  • Clinically significant laboratory findings at screening
  • Use of systemic corticosteroids, antibiotics for respiratory tract infections, high dose inhaled steroids (>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, inhaled sodium cromoglycate or nedocromil sodium, or investigational medicines for defined time periods prior to the screening visit
  • Use of long-term oxygen therapy (12 hours or greater per day)
  • Regular use of nebulized treatment with short-acting bronchodilators
  • Participation in the acute phase of a pulmonary rehabilitation program
  • A know or suspected history of alcohol or drug abuse
  • Affiliation with the investigational site
  • Previous use of GSK573719 or the combination of GSK573719/GW642444
  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: NCT01387230

Locations
United States, Louisiana
GSK Investigational Site
Sunset, Louisiana, United States, 70584
United States, South Carolina
GSK Investigational Site
Easley, South Carolina, United States, 29640
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, 60389
GSK Investigational Site
Gelnhausen, Hessen, Germany, 63571
GSK Investigational Site
Kassel, Hessen, Germany, 34121
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
GSK Investigational Site
Weyhe-Leeste, Niedersachsen, Germany, 28844
GSK Investigational Site
Goch, Nordrhein-Westfalen, Germany, 47574
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
GSK Investigational Site
Solingen, Nordrhein-Westfalen, Germany, 42651
GSK Investigational Site
Koblenz, Rheinland-Pfalz, Germany, 56068
GSK Investigational Site
Teuchern, Sachsen-Anhalt, Germany, 06682
GSK Investigational Site
Leipzg, Sachsen, Germany, 04109
GSK Investigational Site
Leipzig, Sachsen, Germany, 04103
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
GSK Investigational Site
Berlin, Germany, 13187
GSK Investigational Site
Berlin, Germany, 10717
GSK Investigational Site
Berlin, Germany, 10117
GSK Investigational Site
Berlin, Germany, 13086
GSK Investigational Site
Berlin, Germany, 10367
Japan
GSK Investigational Site
Ibaraki, Japan, 319-1113
GSK Investigational Site
Kagawa, Japan, 762-0031
GSK Investigational Site
Kyoto, Japan, 612-0026
GSK Investigational Site
Osaka, Japan, 530-0001
GSK Investigational Site
Tokyo, Japan, 103-0027
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01387230     History of Changes
Other Study ID Numbers: 115408
Study First Received: June 30, 2011
Results First Received: December 19, 2013
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
chronic obstructive pulmonary disease
long acting muscarinic antagonist

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

ClinicalTrials.gov processed this record on August 18, 2014