Losmapimod in Chronic Obstructive Pulmonary Disease Patients Stratified by Fibrinogen.

NCT01541852 | Completed Phase 2

• 2 other identifiers: A0925192011-004936-75
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Vascular Inflammation; FDG PET-CT; COPD; Atherosclerosis; p38 MAP kinase inhibitor

Outcome Measures

Primary Outcomes (3)

• Vascular inflammation on FDG PET-CT

  To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in Vascular inflammation as measured by FDG PET-CT

  Days 0 to Day 112

• Endothelial function as measured by flow mediated dilatation

  To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in endothelial function as measured by flow mediated dilatation

  Days 0 to Day 112

• Arterial structure and plaque characteristics on MRI

  To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in arterial structure and plaque characteristics as measured by MRI (MRI is an optional sub-study and analysis will be based on a sufficient number of datasets).

  Days 0 to Day 112

Secondary Outcomes (7)

• Lung inflammation on FDG PET-CT

  Days 0 to 112

• Fat inflammation on FDG PET-CT

  Days 0 to 112

• Arterial stiffness as measured by arterial tonometry

  Days 0 to 112

• Blood biomarkers of systemic inflammation (Fibrinogen and high sensitivity CRP)

  Days 0 to 112

• Indices of lung function (6 minute walk test and sniff nasal inspiratory pressure)

  Days 0 to 112

Study Arms (2)

Losmapimod

ACTIVE COMPARATOR

7.5mg tablet twice daily

Drug: Losmapimod

Placebo

PLACEBO COMPARATOR

One tablet twice daily

Drug: Placebo

Interventions

Losmapimod DRUG

One tablet of Losmapimod 7.5mg twice daily

Also known as: GW856553

Losmapimod

Placebo DRUG

One tablet twice daily

Also known as: Lactose Monohydrate

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients with a clinical diagnosis of COPD with GOLD Stages 1, 2, 3 or 4, or GOLD-U.
• Patient has FEV1/FVC \< 0.7 post-bronchodilator.
• 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).
• Baseline fibrinogen value of \>2.8 g/L (Klauss method)
• 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%).
• 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.
• Patients who fulfil local imaging centre requirements will be enrolled.

You may not qualify if:

• Inability in the opinion of the PI to provide Informed Consent.
• A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, carotid endarterectomy).
• Patients on daunorubicin, doxorubicin, topotecan, mitoxantrone.
• Previous lung reduction surgery.
• 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.
• A positive pre-trial Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Patients with known chronic infections such as HIV or known active tuberculosis.
• Patients with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).
• Insulin controlled Type 1 or Type 2 diabetics.
• Diabetics on oral hypoglycaemics/diet with HbA1c (DCCT) \> 8% (OR HbA1c (IFCC) \> 64 mmol/mol), at screening. \[note: fasting glucose to be checked again at first FDG-PET/CT scan, and if glucose \> 11mmol/L at that visit, patients will be excluded from trial\]
• 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)
• History of malignancy within the past 5 years (with the exception of localized carcinoma of the skin that has been resected for cure).
• Previous exposure to Losmapimod.
• Patients who have donated more than 500 mL of blood within 2 months prior to the trial medication administration, Visit 3 (Day 1).

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• Technology Strategy Board, United Kingdom: collaborator
• GlaxoSmithKline: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator
• University of Cambridge: collaborator

Study Sites (2)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust

London, London, SW3 6NP, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Atherosclerosis

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; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Joseph Cheriyan, MD

  Cambridge University Hospitals

  PRINCIPAL INVESTIGATOR

• Michael Polkey, MD

  Royal Brompton & Harefield Foundation NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Reader & Hon. Consultant Physician, Clinical Pharmacology/GIM

Study Record Dates

• First Submitted: February 20, 2012
• First Posted: March 1, 2012
• Study Start: June 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: March 17, 2015

Record last verified: 2015-03

Locations

GB (2)