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).

NCT01218126 | Completed Phase 2 Results

• 1 other identifier: 113006
• Study Type: interventional
• Target: 604
• Locations: 8 countries
• Sites: 48

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24

  Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24

• Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24

  Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24

• Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24

  Baseline (Week 0) and Week 12, 24

• 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

  Baseline(Week 0) and Week 12, 24

• Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks

  Baseline (Week 0) and Week 4, 8, 12, 24

Study Arms (4)

losmapimod 2.5 mg

EXPERIMENTAL

losmapimod 2.5 mg

Drug: losmapimod

placebo

PLACEBO COMPARATOR

Drug: placebo

losmapimod 7.5 mg

EXPERIMENTAL

losmapimod 7.5 mg

Drug: losmapimod

losmapimod 15 mg

EXPERIMENTAL

losmapimod 15 mg

Drug: losmapimod

Interventions

losmapimod DRUG

comparison of different dosages of drug 2.5 mg, 7.5 mg or 15 mg

losmapimod 15 mg; losmapimod 2.5 mg; losmapimod 7.5 mg

placebo DRUG

placebo comparison with active

placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• MWD \< 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (48)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

Location

GSK Investigational Site

Torrance, California, 90505, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Saint Charles, Missouri, 63301, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29406-7108, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Richmond, Virginia, 23225, United States

Location

GSK Investigational Site

Mar del Plata, Buenos Aires, 7600, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, S2000DSR, Argentina

Location

GSK Investigational Site

Buenos Aires, C1120AAC, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

Mendoza, 5500, Argentina

Location

GSK Investigational Site

Mendoza, M5500CCG, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

Location

GSK Investigational Site

Ostrava - Poruba, 70868, Czechia

Location

GSK Investigational Site

Prague, 182 00, Czechia

Location

GSK Investigational Site

Tábor, 390 19, Czechia

Location

GSK Investigational Site

Zlín, 762 75, Czechia

Location

GSK Investigational Site

Tallinn, 10138, Estonia

Location

GSK Investigational Site

Tallinn, 13619, Estonia

Location

GSK Investigational Site

Tartu, 51014, Estonia

Location

GSK Investigational Site

Potsdam, Brandenburg, 14467, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Gelnhausen, Hesse, 63571, Germany

Location

GSK Investigational Site

Rüsselsheim am Main, Hesse, 65428, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, 13581, Germany

Location

GSK Investigational Site

Hamburg, 20354, Germany

Location

GSK Investigational Site

Bergen, N-5021, Norway

Location

GSK Investigational Site

Follebu, 2656, Norway

Location

GSK Investigational Site

Harstad, 9480, Norway

Location

GSK Investigational Site

Levanger, 7600, Norway

Location

GSK Investigational Site

Stavanger, 4011, Norway

Location

GSK Investigational Site

Trondheim, 7030, Norway

Location

GSK Investigational Site

Seoul, 100-032, South Korea

Location

GSK Investigational Site

Seoul, 130-702, South Korea

Location

GSK Investigational Site

Seoul, 130-848, South Korea

Location

GSK Investigational Site

Seoul, 134-701, South Korea

Location

GSK Investigational Site

Seoul, South Korea

Location

GSK Investigational Site

Donetsk, 83003, Ukraine

Location

GSK Investigational Site

Donetsk, 83099, Ukraine

Location

GSK Investigational Site

Kiev, 03680, Ukraine

Location

GSK Investigational Site

Kyiv, 03115, Ukraine

Location

GSK Investigational Site

Kyiv, 03680, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 31197640 DERIVED

• 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.

  PMID: 24461903 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 11, 2010
• Study Start: November 4, 2010
• Primary Completion: December 21, 2011
• Study Completion: December 21, 2011
• Last Updated: February 6, 2018
• Results First Posted: January 4, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

KR (5); CZ (4); ES (3); UA (5); US (8); NO (6); AR (7); DE (10)