Subjects with myocardial infarction without ST-segment elevation MedDRA version: 13.1 Level: LLT Classification code 10064347 Term: Non ST segment elevation myocardial infarction System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: GW856553
Product Code: GW856553
Pharmaceutical Form: Tablet
INN or Proposed INN: Losmapimod
Current Sponsor code: GW856553
Concentration unit: mg milligram(s)
Concentration type: equal
C
Sponsors
GlaxoSmithKline R&D Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with a NSTEMI, defined as: • symptoms (e.g. chest pain, dyspnea) consistent with acute coronary syndrome, lasting at least 10 minutes, with most recent symptoms occurring within the 24 hours prior to presentation, • without persistent ST-segment elevation on admission 12-lead ECG, and • with Troponin (T or I) > 2x the upper limit of normal (ULN) for the local institution within 18 hours of presentation. 2. Subject able to be randomized within 18 hours of presentation. 3. Subjects to be managed with an early invasive strategy, with PCI likely to occur at least 2 hours after the start of dosing [subjects who do not undergo PCI will not be withdrawn from study]. 4. Male or female subject who is 45 years of age or older. 5. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction [ejection fraction (EF) < 30%] regardless of symptomatic status. 2. Suspected aortic dissection. 3. Severe aortic stenosis or other severe valvular disease. 4. Current known life-threatening condition other than vascular disease (e.g. severe chronic airways disease) that may prevent a subject from completing the study. 5. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic or acute inflammation (e.g. inflammatory bowel disease, osteomyelitis, pneumonia, sepsis etc.). Intermittent conditions treated with short-term oral antibiotics (e.g. typical URI), or conditions that are not currently exacerbated (e.g. gout with no current flair) may be included. 6. History of myopathy or rhabdomyolysis. 7. Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 8. Known to be Hepatitis B or Hepatitis C positive. 9. Current or anticipated use of steroids (oral or IV). Inhaled, intranasal and topical steroids are allowed. A single prophylactic dose of systemic steroid is allowed at time of PCI for subjects with contrast allergy. 10. Current or anticipated use of BCRP substrates with a narrow therapeutic index (e.g. daunorubicin, doxorubicin, topotecan, mitoxantrone); see Section 9.2 of the protocol 11. Previously diagnosed cancer that has not been in complete remission for at least 5 years. Localised carcinomas of the skin and carcinoma in situ of the cervix that have been resected or ablated for cure are not exclusionary. 12. Known alcohol or drug abuse within the past 6 months. 13. Previous exposure to GW856553. 14. Use of another investigational product within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of IP in the current study. 15. Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication noncompliance). 16. Unwillingness or inability to follow the procedures outlined in the protocol. 17. Previous MI or coronary artery bypass graft (CABG) surgery. 18. History of kidney transplant or a history of contrast nephropathy. 19. Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to: • Intracranial aneurysm clips (except Sugita) or other metallic objects, • History of intra- orbital metal fragments that have not been removed by an MD, • Pacemakers and non-MR compatible heart valves, • Inner ear implants, • History of claustrophobia in MR. 20. Allergy to MRI contrast enhancement agent (gadolinium). 21. Estimated creatinine clearance by Cockroft-Gault formula < 30 mL/min.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the safety of GW856553 in subjects with NSTEMI. 2. To assess the effects of GW856553 on biomarkers of inflammation in subjects with NSTEMI over the 12 weeks of treatment. 3. To assess the effects of GW856553 on infarct size and cardiac function during the peri-infarct period and during the ensuing 12 weeks of treatment. ;Secondary Objective: Various exploratory endpoints, including coronary pressure/flow, PK/PD and quality of life will be evaluated. ;Primary end point(s): Safety Endpoints • A safety evaluation will be made by assessment of all adverse events, major adverse cardiovascular events (MACE) as defined in Section 11.3, safety laboratory tests (including liver function values), vital signs and 12-lead ECG parameter Inflammatory Endpoints •hsCRP at Week 12 Myocardial Infarct Sizeand Cardiac Function Endpoints •cTnI AUC over 72 hours post-randomization or until hospital discharge (whichever comes first). | — |
Countries
Germany, Netherlands, Spain, United Kingdom
Outcome results
None listed