Acute coronary syndrome MedDRA version: 20.0 Level: PT Classification code 10051592 Term: Acute coronary syndrome System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Brilique 90 mg
Product Name: Brilique 90 mg
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: Ticagrelor
CAS N
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To participate in this trial, subjects must meet all of the following criteria: 1.Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post-menopausal) 2.Age between 18 and 65 years inclusive 3.Non-smokers 4.Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg 5.In good health as determined by a medical history, physical examination, vital signs and clinical laboratory test results, including renal and liver function, and full blood count 6.Provision of informed consent before any trial-related activity Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from participation in the study: 1. Any history of cancer, diabetes or, in the opinion of the investigator, clinically-significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders 2. Any history of either significant multiple drug allergies or known allergy to the study drugs or any medicine chemically related to the study drugs 3. A clinically-significant illness within 4 weeks of randomisation 4. Any clinically-significant abnormal laboratory test results at screening, in the opinion of the investigator 5. A supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg 6. A supine heart rate at screening, after resting for 5 minutes, outside the range of 50-100 beats/min 7. Receipt of any prescribed or over-the-counter systemic or topical medication within 48 hours prior to the start of dosing 8. Planned or expected requirement, during the next 3 months (at randomisation, or 3 weeks at the start of period 2), for any systemic or topical prescribed drug, or for systemic or topical over-the-counter NSAID, corticosteroid, antihistamine or any other drug that could affect inflammation, thrombosis or haemostasis in the opinion of the investigator. 9. Receipt of an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three months preceding the start of dosing. When reconfirming eligibility at the start of period 2, receipt of aspirin (aspirin lysine), ticagrelor or endotoxin during period 1 of this study will not be counted for this purpose. 10. Any donation of blood or plasma in the month preceding the start of dosing. 11. A history of alcohol or drug abuse 12. Mental incapacity or language barriers that preclude adequate understanding 13. Any other factor that, in the opinion of the investigator, would affect the participant’s ability to safely and reliably complete the study, or would affect the scientific validity of the results obtained.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint will be plasma tumour necrosis factor alpha TNF-a (assessed at 2 hours post-endotoxin injection) compared between participants receiving no drug, aspirin (aspirin lysine) 20 mg BD, aspirin (aspirin lysine) 75 mg OD and aspirin (aspirin lysine) 300 mg OD.;Timepoint(s) of evaluation of this end point: Serial measurements from 0 to 6 hours after intravenous endotoxin administration, 10 days after commencing study medication.;Main Objective: The principal objective of this study is to assess the effects of different aspirin dosing regimens (no aspirin, aspirin 20 milligrams twice-daily, aspirin 75 milligrams once-daily or aspirin 300 mg once-daily) on the levels of the inflammatory protein tumour necrosis factor alpha, during the stimulation of the immune system by intravenous injection of a pro-inflammatory substance, endotoxin.;Secondary Objective: The secondary objectives of this study are to assess the effects of different aspirin dosing regimens (no aspirin, aspirin 20 milligrams twice-daily, aspirin 75 milligrams once-daily or aspirin 300 mg once-daily; each given with or without a second drug, ticagrelor) on the levels of a range of inflammatory factors, platelet function and clotting mechanisms, during the stimulation of the immune system by intravenous injection of a pro-inflammatory substance, endotoxin. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Plasma interleukin-6 from 0 to 6 hours after endotoxin administration 2. Area under the curve (AUC) of the graph, from 0 to 6 hours after endotoxin administration, of serum C-reactive protein 3. Leukocyte count, from 0 to 6 hours after endotoxin administration 4. Serum thromboxane B2, from 0 to 6 hours after endotoxin administration 5. Serum prostaglandin E2, from 0 to 6 hours after endotoxin administration 6. AUC of the graph, from 0 to 6 hours after endotoxin administration, of urine prostacyclin metabolite 7. AUC of the graph, from 0 to 3 hours after endotoxin administration, of bleeding time 8. Mean maximum platelet aggregation responses to arachidonic acid (AA), collagen and adenosine diphosphate (ADP), from 0 to 6 hours after endotoxin administration. Secondary endpoints will be compared between: 1. Participants receiving no drug, aspirin (aspirin lysine) 20 mg twice-daily (BD), aspirin (aspirin lysine) 75 mg once-daily (OD) and aspirin (aspirin lysine) 300 mg OD. 2. Participants receiving ticagrelor 90 mg BD, aspirin (aspirin lysine) 20 mg BD plus ticagrelor 90 mg BD, aspirin (aspirin lysine) 75 mg OD plus ticagrelor 90 mg BD, and aspirin (aspirin lysine) 300 mg OD plus ticagrelor 90 mg BD. 3. Participants receiving no drug and ticagrelor 90 mg BD. 4. Participants receiving aspirin (aspirin lysine) 20 mg BD, and aspirin (aspirin lysine) 20 mg BD plus ticagrelor 90 mg BD. 5. Participants receiving aspirin (aspirin lysine) 75 mg OD, and aspirin (aspirin lysine) 75 mg OD plus ticagrelor 90 mg BD. 6. Participants receiving aspirin (aspirin lysine) 300 mg OD, and aspirin (aspirin lysine) 300 mg OD plus ticagrelor 90 mg BD. 7. Participants receiving no drug, aspirin (aspirin lysine) 20 mg | — |
Countries
United Kingdom
Contacts
Public ContactSam Walmsley (CRIO)
Sheffield Teaching Hospitals NHS Foundation Trust
Outcome results
None listed