Clinical trial NCT01218126: 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).
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-10-11
Enrollment: 604
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24
timeFrame: Baseline (Week 0) and Week 4, 12, 24
Secondary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24
timeFrame: Baseline (Week 0) and Week 12, 24
measure: 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
timeFrame: Baseline(Week 0) and Week 12, 24
measure: Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks
timeFrame: Baseline (Week 0) and Week 4, 8, 12, 24
measure: Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks
timeFrame: Baseline (Week 0) and Week 4, 8, 12, 24
measure: Total Number of Exacerbations Over 24 Weeks
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Charles
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Tucuman
country: Argentina
facility: GSK Investigational Site
city: Ostrava - Poruba
country: Czechia
facility: GSK Investigational Site
city: Praha 8
country: Czechia
facility: GSK Investigational Site
city: Tabor
country: Czechia
facility: GSK Investigational Site
city: Zlin
country: Czechia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Potsdam
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Gelnhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Ruesselsheim
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Follebu
country: Norway
facility: GSK Investigational Site
city: Harstad
country: Norway
facility: GSK Investigational Site
city: Levanger
country: Norway
facility: GSK Investigational Site
city: Stavanger
country: Norway
facility: GSK Investigational Site
city: Trondheim
country: Norway
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Largajolli A, Beerahee M, Yang S. Bayesian approach to investigate a two-state mixed model of COPD exacerbations. J Pharmacokinet Pharmacodyn. 2019 Aug;46(4):371-384. doi: 10.1007/s10928-019-09643-6. Epub 2019 Jun 13.
citation: Watz H, Barnacle H, Hartley BF, Chan R. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014 Jan;2(1):63-72. doi: 10.1016/S2213-2600(13)70200-5. Epub 2013 Dec 5.