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).

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: placebo; Drug: losmapimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT01218126

113006

Details and patient eligibility

About

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.

Enrollment: 604 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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604 participants in 4 patient groups, including a placebo group

losmapimod 2.5 mg

Experimental group

Description:

losmapimod 2.5 mg

Treatment:

Drug: losmapimod

placebo

Placebo Comparator group

Treatment:

Drug: placebo

losmapimod 7.5 mg

Experimental group

Description:

losmapimod 7.5 mg

Treatment:

Drug: losmapimod

losmapimod 15 mg

Experimental group

Description:

losmapimod 15 mg

Treatment:

Drug: losmapimod