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).

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-centre, Dose Ranging 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01218126
• Other study ID #: 113006
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2010
• Last updated: January 10, 2018
• Start date: November 4, 2010
• Est. completion date: December 21, 2011

Study information

• Verified date: January 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 604
• Est. completion date: December 21, 2011
• Est. primary completion date: December 21, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

• a1-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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• losmapimod
comparison of different dosages of drug 2.5 mg, 7.5 mg or 15 mg
• placebo
placebo comparison with active

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Tucuman
Czechia	GSK Investigational Site	Ostrava - Poruba
Czechia	GSK Investigational Site	Praha 8
Czechia	GSK Investigational Site	Tabor
Czechia	GSK Investigational Site	Zlin
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Gelnhausen	Hessen
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Ruesselsheim	Hessen
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Norway	GSK Investigational Site	Bergen
Norway	GSK Investigational Site	Follebu
Norway	GSK Investigational Site	Harstad
Norway	GSK Investigational Site	Levanger
Norway	GSK Investigational Site	Stavanger
Norway	GSK Investigational Site	Trondheim
Ukraine	GSK Investigational Site	Donetsk
Ukraine	GSK Investigational Site	Donetsk
Ukraine	GSK Investigational Site	Kiev
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	Saint Charles	Missouri
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Czechia,  Estonia,  Germany,  Korea, Republic of,  Norway,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24	Exercise tolerance was assessed using the 6MWD. If a participant 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).	Baseline (Week 0) and Week 4, 12, 24
Secondary	Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at 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).	Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24
Secondary	Change From Baseline in Forced Vital Capacity (FVC) at 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).	Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24
Secondary	Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24	The SGRQ-C questionnaire had 14 questions of COPD and participant had to rate each question. These 14 questions were separated to evaluate the three components of SGRQ-C. These three components were symptom component (question 1 to 7), activity component (question 9 and 12) and impact component (question 8, 10, 11, 13 and 14). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Change from Baseline was calculated as the specified time point value minus the Baseline value. Baseline visit was Visit 2 (Week 0).	Baseline (Week 0) and Week 12, 24
Secondary	Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 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).	Baseline(Week 0) and Week 12, 24
Secondary	Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks	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.	Baseline (Week 0) and Week 4, 8, 12, 24
Secondary	Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks	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.	Baseline (Week 0) and Week 4, 8, 12, 24
Secondary	Total Number of Exacerbations Over 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.	Up to 24 weeks

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