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).
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: losmapimod; placebo
Intervention description: comparison of different dosages of drug 2.5 mg, 7.5 mg or 15 mg; placebo comparison with active
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 604.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

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