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Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-centre, Dose Ranging Study to Evaluate the Efficacy and Safety of Losmapimod Tablets Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD).

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01218126
First Posted: October 11, 2010
Last Update Posted: May 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
Randomised, double-blind, parallel-group, multi-centre study evaluating three doses of losmapimod (2.5mg, 7.5 mg and 15 mg) twice daily (BID) versus placebo on exercise tolerance. Eligible subjects will be randomised to treatment after a one-week run-in period. The duration of the treatment period is 24 weeks. An estimated 1000 subjects will be screened to reach the target enrolment of approximately 600 randomised subjects.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive Drug: losmapimod Drug: placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Efficacy and Safety of Losmapimod (GW856553) Tablets Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD).

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from Baseline in Six minute walk distance (6MWD) at Week 4, 12 and 24 [ Time Frame: Baseline (Week 0) and Week 4, 12, 24 ]
    Exercise tolerance was assessed using the 6MWD. If a participants was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = [100 x (6MWD2 - 6MWD1)]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).


Secondary Outcome Measures:
  • Change from baseline in Forced expiratory volume in 1 sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 [ Time Frame: Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24 ]
    Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Pre and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.. Baseline visit was Visit 2 (Week 0).

  • Change from baseline in Forced vital capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 [ Time Frame: Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24 ]
    FVC is the total amount of air exhaled during the lung function test. and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.. Baseline visit was Visit 2 (Week 0).

  • Change from baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 [ Time Frame: Baseline (Week 0) and Week 12, 24 ]
    The SGRQ-C is a newly developed version of the well-established SGRQ instrument. This version was developed to reduce the participant burden, reduce missing data and improve the psychometric properties, whilst retaining the established properties of the instrument. In contrast to the original, it is a COPD specific instrument and was been reduced from the original 50 items. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).

  • Change from baseline in inspiratory capacity, residual volume, total lung capacity , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 [ Time Frame: Baseline(Week 0) and Week 12, 24 ]
    A plethysmograph is an instrument for measuring changes in volume within an organ or whole body (usually resulting from fluctuations in the amount of blood or air it contains). Plethysmography was used to assess IC, RV, TGV at FRC, SLV, and TLC. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).

  • Least square mean ratio to Baseline of plasma fibrinogen over 24 weeks [ Time Frame: Baseline (Week 0) and Week 4, 8, 12, 24 ]
    Least square mean ratio to Baseline of plasma fibrinogen was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits.

  • Least square mean ratio to Baseline of high sensitivity C-reactive protein (HsCRP) over 24 weeks [ Time Frame: Baseline (Week 0) and Week 4, 8, 12, 24 ]
    Least square mean ratio to Baseline of HsCRP was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits.

  • Number of participants with On-treatment Exacerbations [ Time Frame: Up to 24 weeks ]
    An exacerbation of COPD is defined as a worsening of COPD symptoms requiring changes to normal treatment (other than increased use of relief salbutamol/albuterol) including antimicrobial therapy, short courses of oral steroids, other bronchodilator therapy and/or emergency treatment or hospitalization.


Enrollment: 605
Study Start Date: November 1, 2010
Study Completion Date: December 21, 2011
Primary Completion Date: December 1, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: losmapimod Drug: losmapimod
comparison of different dosages of drug
Placebo Comparator: placebo Drug: placebo
placebo comparison with active

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society
  • FEV1/FVC ratio of ≤0.70
  • FEV1 ≤ 80% of predicted normal
  • 6MWD < 350m
  • male or female outpatients aged ≥40 years of age
  • current or prior history of ≥10 pack-years of cigarette smoking
  • aspartate transaminase (AST) or alanine transaminase (ALT) <2x Upper Limit Normal (ULN)
  • alkaline phosphatase (alk phos), and bilirubin <1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  • QTc <450 msec* on baseline ECG. For subjects with baseline complete bundle branch block, the QTc must be <480msec* on baseline ECG.

Exclusion Criteria:

  • current diagnosis of asthma
  • pregnant or lactating
  • α1-antitrypsin deficiency
  • lung resection
  • chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD
  • exacerbation of COPD within previous 12 weeks
  • treatment with roflumilast within previous 2 weeks and throughout the treatment period
  • lower respiratory tract infection that required the use of antibiotics within previous 12 weeks
  • long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day
  • participation in the acute phase of a Pulmonary Rehabilitation Program within 12 weeks or planned during the study
  • carcinoma that has not been in complete remission for at least 5 years
  • current or chronic history of liver disease
  • positive Hepatitis B surface antigen or positive Hepatitis C antibody
  • Body Mass Index (BMI) > 35
  • known or suspected history of alcohol or drug abuse within the last 2 years
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01218126


  Show 48 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113006
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: 113006
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113006
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: 113006
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: 113006
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: 113006
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113006
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01218126     History of Changes
Other Study ID Numbers: 113006
First Submitted: October 7, 2010
First Posted: October 11, 2010
Last Update Posted: May 2, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
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.

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes