E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune response to endotoxin influenced by anti-platelet medications. |
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E.1.1.1 | Medical condition in easily understood language |
Immune response to endotoxin influenced by anti-platelet medications. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011968 |
E.1.2 | Term | Decreased immune responsiveness |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Do the anti-clotting medications, ticagrelor and clopidogrel, also have an effect on the immune response? |
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E.2.2 | Secondary objectives of the trial |
If ticagrelor and/or clopidogrel do affect immune response, by what mechanism does this occur? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post menopausal). Age between 18 and 65 years inclusive. Non smokers. Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg. Subjects are to be 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. Subjects have given their informed consent before any trial-related activity. |
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E.4 | Principal exclusion criteria |
In the opinion of the investigator, subjects with a history of cancer, diabetes or clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric, or other major disorders. Subjects with a history of significant multiple drug allergies or with a known allergy to the study drugs or a medicine chemically related to the study drugs Subjects who have had a clinically significant illness within 4 weeks of dosing Subjects taking regular medicines including NSAIDs, antibiotics, aspirin or anticoagulant therapy. Any clinically significant abnormal laboratory test results at screening. Subjects who have a supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg. Subjects who have a supine heart rate at screening, after resting for 5 minutes, outside the range of 50-100 beats/min. Subjects who have received any prescribed systemic or topical medication within two weeks prior to the start of dosing. Limited use of paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) prior to the initiation of the study will not necessarily require exclusion unless there is an ongoing requirement for these medications. Subjects who have received 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. Subjects who have donated any blood or plasma in the month preceding the start of dosing. Subjects who have a history of alcohol or drug abuse. Subjects with mental incapacity or language barriers which preclude adequate understanding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Area under the curve of graph of CRP over time. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 24 hours following administration of endotoxin |
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E.5.2 | Secondary end point(s) |
White blood cell count, levels of cytokines (IL-1ra, IL-6, IL-8, IL-10 and TNF-alpha) markers of leucocyte phenotype and function (leucocyte expressed CCR2, CXCR1, CXCR2, CXCR3, CD11b, CD14, CD16, L-selectin and TLR-4), markers of leucocyte degranulation (neutrophil elastase and myeloperoxidase), markers of platelet activity (P2Y12 receptor reactivity, platelet P-selectin expression, formation of platelet leucocyte aggregates and levels of thrombopoietin) and measurements of coagulation (fibrinogen, D-dimer and prothrombin fragment). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No antiplatelet medication |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |