A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging

NCT00633022 | Completed Phase 2 Results

• 1 other identifier: PM1111138
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 4

Brief Summary

This study is being conducted to assess the potential anti-inflammatory effects of a 3-month treatment with GW856553, on the inflammatory activity within the aorta and carotid plaques, as assessed by FDG-PET/CT.

Conditions

Atherosclerosis

Keywords

FDG-PET/CT, atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline of Mean of Maximum Tissue to Background Ratio (TBR) in the Qualifying Artery, Following 12 Weeks of Treatment in the Setting of Chronic Statin Therapy

  Qualifying artery was defined as the artery (left or right carotid or ascending aorta) with the highest segmental mean of maximum (max) TBR at Baseline. The TBR of the qualifying segment was to be ≥ 1.6. If more than one artery qualified, the hottest (greatest mean of max TBR) artery was the qualifying artery. Baseline was defined as the value between Days -14 to -1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.

  Baseline (Days -14 to -1) and up to Week 12

Secondary Outcomes (9)

• Change From Baseline of the 'Most Diseased Segment (MSD)' Average Maximum TBR in the Qualifying Artery Following 12 Weeks of Treatment With GW856553 or Placebo in the Setting of Chronic Statin Therapy

  Baseline (Days -14 to -1) and up to Week 12

• Change From Baseline in Blood Concentration of High Sensitivity C-reactive Protein (Hs-CRP)

  Baseline (Day 1) and Days 7, 14, 21, 28, 42, 56, 70, 84

• Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points

  Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

• Mean Heart Rate at Indicated Time Points

  Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

• Number of Participants With 12-lead Electrocardiogram (ECG) Findings

  Days 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

Study Arms (3)

LOSMAPIMOD 7.5 MG TWICE DAILY

EXPERIMENTAL

Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks

Drug: LOSMAPIMOD 7.5 MG

Placebo

PLACEBO COMPARATOR

Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.

Drug: Placebo

LOSMAPIMOD 7.5 MG ONCE DAILY

EXPERIMENTAL

Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.

Drug: LOSMAPIMOD 7.5 MG

Interventions

LOSMAPIMOD 7.5 MG DRUG

GW856553 tablets (wet granulation formulation) are available as white, film coated, round, convex tablets manufactured using micronised GW856553X active substance. Tablets are available containing 7.5 mg of GW856553X and are packed into high-density polyethylene (HDPE) bottles.

LOSMAPIMOD 7.5 MG ONCE DAILY; LOSMAPIMOD 7.5 MG TWICE DAILY

Placebo DRUG

Placebo tablets (wet granulation formulation) are available as white, film coated, round, convex tablets manufactured using micronised substance to visually match the active GW856553 tablets are also available. Tablets are packed into high-density polyethylene (HDPE) bottles.

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male and female subjects, between 50 and 80 years of age, inclusive, with a body weight \> 50 kg and body mass index (BMI) between 19 and 35 kg/m2
• Subjects who have:
• experienced a CV event (acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, TIA, carotid endarterectomy), but have been clinically stable for at least 6 months since that event,
• or, have peripheral vascular disease (PVD), as indicated by
• symptoms of claudication and either a positive imaging/treadmill test, or
• reduced ankle branchial pressure index,
• or, have a diagnosis of CAD corroborated by stress testing (exercise or pharmacological) or any other confirmed diagnosis of atherosclerotic arterial disease
• Individuals who have experienced a CV event or have PVD will be given preference for enrolment in the study, if they also have one of the following:
• metabolic syndrome, as defined by NCEP ATP III
• Framingham score \> 20
• Current smokers (at least 1pack/day)
• Well-controlled diabetes, defined for the purposes of this study as HbA1c \<= 8%, or fasting blood glucose \<= 126mg/dL (7mmol/L)
• Subjects must be on a stable dose of statin for at least 3 months prior to first dose of study medication. Subjects must be capable of continuing statin therapy from screening until the final follow up visit.
• Either carotid or aortic TBR ³ 1.6, as measured on FDG-PET/CT, signifying active inflammation.
• AST and 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%).

You may not qualify if:

• History of heart failure defined as NYHA class II - IV or those with known severe LV systolic dysfunction (EF\<30%) regardless of symptomatic status
• Subjects with atrial fibrillation (AF) at screening will be excluded.
• Insulin controlled Type 1 or Type 2 diabetics
• Diabetics with fasting glucose \> 126mg/dL (7mmol/L) or HbAc1 levels \> 8%, at screening. \[note: fasting glucose to be checked again at first FDG-PET scan, and if glucose \> 11mmol/L at that visit, subject will be excluded from study\]
• Positive pre-study hepatitis B surface antigen or positive hepatitis C antibody results 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).
• Renal impairment with creatinine clearance of \<40 ml/min at screening, or history of kidney transplant or history of contrast nephropathy.
• Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).
• Subjects with chronic infections such as HIV, gingivitis, periodonitis, prostatitis, gastritis, and urinary tract infections, or any active diseases, including active tuberculosis or a history of active tuberculosis.
• Subjects with any acute infection, symptoms suggestive of sinusitis, or significant trauma (burns, fractures)
• History of malignancy within the past 5 years, other than non-melanoma skin cancer.
• History of skeletal muscle myopathy or rhabdomyolysis
• Previous exposure to GW856553.
• Current use of steroids (inhaled or oral)
• Subjects who have donated more than 500 mL of blood within 56 days prior to the study medication administration.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

GSK Investigational Site

London, E1 1B3, United Kingdom

Location

GSK Investigational Site

London, Se1 7EH, United Kingdom

Location

Related Publications (1)

• Elkhawad M, Rudd JH, Sarov-Blat L, Cai G, Wells R, Davies LC, Collier DJ, Marber MS, Choudhury RP, Fayad ZA, Tawakol A, Gleeson FV, Lepore JJ, Davis B, Willette RN, Wilkinson IB, Sprecher DL, Cheriyan J. Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients with atherosclerosis. JACC Cardiovasc Imaging. 2012 Sep;5(9):911-22. doi: 10.1016/j.jcmg.2012.02.016.

  PMID: 22974804 BACKGROUND

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

Atherosclerosis

Interventions

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

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2008
• First Posted: March 11, 2008
• Study Start: June 2, 2008
• Primary Completion: December 3, 2009
• Study Completion: December 3, 2009
• Last Updated: October 17, 2018
• Results First Posted: October 17, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (4)