None listed
Conditions
Brief summary
E5555 is a small molecule that inhibits activation of protease-activated receptor 1 (PAR-1), the main thrombin receptor on platelets, preventing platelet aggregation (which is essential to clot formation); preventing platelet activation and release of inflammatory substances locally and into the bloodstream; reducing generation of more thrombin. These actions suggest that it may be a useful adjunct to current therapy for Acute Coronary Syndrome (ACS) and not a replacement for any currently established forms of treatment for Acute Coronary Syndrome (ACS). This study will look at the safety and efficacy of E5555 in patients admitted to hospital with symptoms, and objective evidence, of acute coronary syndrome, for a period of 12 weeks. There will also be a further visit 4 weeks after the last intake of study drug. The entire study participation will be 16 weeks. The patients would be seen initially on a daily basis during the hospitalisaiton period, and once discharged, asked to attend clinic for a total of 5 visits over the outpatient phase of the study. Visits will be between 2 and 4 weeks apart. The type of assessments at each visit are what would be typically undergone by cardiac patients - physical examinations; blood pressure, pulse, temperature, electrocardiongrams (up to 11 in total); blood draws (8 in total) and regular intake of study medication (three tables taken once a day with breakfast). Continuous electrocardiogram (ECG) monitoring (Holter monitoring) will also be done for the first 48 hours following randomisation. Any adverse events will be recorded, as will details of concurrent medication. There is a sub-study being undertaken by selected sites, and participation in this will be optional for the patients. This sub-study would entail additional blood samples being taken for pharmacokinetics (PK) and platelet aggregation purposes
Interventions
After a single, orally administered, loading dose of E5555 400 mg on day 1 (four 100 mg active tablets) or placebo 400 mg (four 100 mg placebo tablets), E5555 will be administered orally (po), once daily from day 2 to day 84 (week 12). E5555 50 mg (one 50 mg active and two 100 mg placebo tablets), E5555 100 mg (one 50 mg placebo, one 100 mg active and one 100 mg placebo tablet) and E5555 200 mg (one 50 mg placebo and two 100 mg active tablets). Control arm: Placebo (one 50 mg placebo and two 100
After a single, orally administered, loading dose of E5555 400 mg on day 1 (four 100 mg active tablets) or placebo 400 mg (four 100 mg placebo tablets), E5555 will be administered orally (po), once daily from day 2 to day 84 (week 12). E5555 50 mg (one 50 mg active and two 100 mg placebo tablets), E5555 100 mg (one 50 mg placebo, one 100 mg active and one 100 mg placebo tablet) and E5555 200 mg (one 50 mg placebo and two 100 mg active tablets). Control arm: Placebo (one 50 mg placebo and two 100 mg placebo tablets).
Sponsors
Eisai Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
The study will include men and women, aged between 45 and 80 years, inclusive, who have been admitted to hospital with a diagnosis of non-ST segment elevation Acute Coronary Syndrome (ACS). There must be symptoms typical of unstable angina, and able to be randomised and treated within 24 hours of the onset of the pain resulting in this admission. In addition to this, cardiac enzymes must be elevated or electrocardiogram (ECG) changes compatible with ischemia must be present
Exclusion criteria
Inability or unwillingness to provide fully informed consent to study participation; pregnancy; any history of a bleeding type condition or disorder; severe heart failure or heart rhythm problems; any cardiac surgery within the 12 weeks before admission or any cardiac event, such as heart attack or unstable angina, within the 30 days prior to admission; unstable diabetes requiring frequent alterations to prescribed anti-diabetic medication; any history of liver or kidney problems which causes significant abnormal blood results; the use of any medications shown to have potential adverse interactions with the study medication; recent significant infection or history of chronic infections requiring continuous antibiotic treatment; history of cancer unless adequate treated with no evdence of disease for at least 2 years and participation in any other clinical trial within the 30 days prior to admission
Outcome results
None listed