The main purpose of this study is to determine the effect of Losmapimod on blood vessels in patients with Chronic Obstructive Pulmonary Disease (COPD). Although COPD is a lung disease, it is also associated with an increased risk of cardiovascular disease (e.g. heart attacks and stroke). The investigators believe that this is a result of inflammation within the body, which damages the lining (endothelium) and walls of blood vessels. These changes can promote the development of fatty deposits within the walls of arteries (atherosclerosis) which can rupture and block arteries causing damage.

The study aims to enrol sufficient COPD subjects (stratified by fibrinogen level) so that 60 patients complete the study. Study patients will have a 50% chance of receiving either Losmapimod or Placebo. Patients will be expected to attend for up to 12 visits, over a 24 week period. The visits consist of an initial screening visit, and 2 pre-dose imaging visits to include a PET-CT scan and an optional MRI scan. The next 7 visits (at 2-4 weekly intervals) involve blood tests and safety evaluations. A number of procedures including heart tracings (ECGs), non-invasive vascular measurements and lung function tests at the start and at the end of the study. Repeat imaging with PET-CT and MRI will be performed at the end of the study and a follow-up visit.

The purpose of the study is to see if the study medication has a beneficial effect on vascular function and structure. It is envisaged that this trial will help define more evolutionary biomarkers to focus on to help COPD patients in the future.

Inclusion Criteria:

1. Male or female patients between 50 and 85 years of age inclusive at screening, with a body weight ≥ 45 kg and BMI ≤35 kg/m2.
2. Patients with a clinical diagnosis of COPD with GOLD Stages 1, 2, 3 or 4, or GOLD-U.
3. Patient has FEV1/FVC < 0.7 post-bronchodilator.
4. Patient is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).
5. Baseline fibrinogen value of >2.8 g/L (Klauss method)
6. ALT < 2xULN at screening; alkaline phosphatase and bilirubin > 1.5xULN at screening (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
7. Patients must have a QTc <450 msec on screening (V1) ECG (using average value of triplicate ECGs). For patients with complete Right bundle branch block, the QTc must be <480msec on Screening V1 ECG. Patients with other ECG findings will be excluded if warranted at the discretion of the CI/PI. QTc readings will be QTcF.
8. Patients who fulfil local imaging centre requirements will be enrolled.

Exclusion Criteria:

The presence of any of the following will preclude patient inclusion:

1. Inability in the opinion of the PI to provide Informed Consent.
2. A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, carotid endarterectomy).
3. Patients on daunorubicin, doxorubicin, topotecan, mitoxantrone.
4. Previous lung reduction surgery.
5. Patients with known clinically significant pulmonary diagnoses in which inflammation is thought to play a role including diagnosis of bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung disease, or α1-antitrypsin deficiency.
6. A positive pre-trial Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
7. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
8. Patients with known chronic infections such as HIV or known active tuberculosis.
9. Patients with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).
10. Insulin controlled Type 1 or Type 2 diabetics.
11. Diabetics on oral hypoglycaemics/diet with HbA1c (DCCT) > 8% (OR HbA1c (IFCC) > 64 mmol/mol), at screening. [note: fasting glucose to be checked again at first FDG-PET/CT scan, and if glucose > 11mmol/L at that visit, patients will be excluded from trial]
12. Participation in a previous research trial in the last 3 years which involved exposure to significant ionising radiation (i.e. cumulative research radiation dose >5 mSv)
13. History of malignancy within the past 5 years (with the exception of localized carcinoma of the skin that has been resected for cure).
14. Previous exposure to Losmapimod.
15. Patients who have donated more than 500 mL of blood within 2 months prior to the trial medication administration, Visit 3 (Day 1).
16. Participation in a clinical trial where the patient has received a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of the drug (whichever is longer) prior to the first dose of trial medication, Visit 3 (Day 1).
17. History of alcohol/drug abuse or dependence within 6 months of the trial, Screening Visit 1 (Day -45 to -14).
18. Women of childbearing potential are excluded from this trial.
19. Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern.
20. Use of systemic corticosteroids (oral or IV) 4 weeks prior to Visit 2 (Day -14 to -1).