Study to See if Platelet Transfusion Stop or Lessen the Effect of the Drug on Platelets

Study Overview
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Brief Summary
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Study to see if platelet transfusion stop or lessen the effect of the drug on platelets

Detailed Description
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A open label, randomized, crossover and potential parallel, single dose study of ticagrelor 180 mg and acetylsalicylic acid (ASA) in healthy volunteers followed by autologous in vivo platelet transfusion to determine the effects of platelet supplementation on the reversibility of platelet inhibition

Official Title
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A Open Label, Randomized, Crossover and Potential Parallel, Single Dose Study of Ticagrelor 180 mg and Acetylsalicylic Acid (ASA) in Healthy Volunteers Followed by Autologous in Vivo Platelet Transfusion to Determine the Effects of Platelet Supplementation on the Reversibility of Platelet Inhibition

Conditions
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Inhibition on Platelet Aggregation

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel
* Drug: ASA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study specific procedures Healthy male and/or female volunteers aged 18 to 50 years, inclusive, with suitable veins for cannulation or repeated venipuncture. (Healthy as determined by medical history and physical examination, laboratory parameters, electrocardiogram (ECG) perform Have a body mass index (BMI) between 18 and 35 kg/m2 (inclusive) and weigh at least 50 kg and no more than 120 kg Exclusion Criteria: ADP induced platelet aggregation <60% prior to platelet apheresis History of peptic ulcer disease Healthy volunteers with a propensity to bleed (eg, due to recent trauma, recent surgery, active or recent gastrointestinal bleeding or moderate hepatic impairment) Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the investigational product Current smokers, those who have smoked or used nicotine products within the previous 3 months and those who tested positive for cotinine at screening or at admission to the study center

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Ticagrelor with Platelet transfusion | Drug: Ticagrelor<br>* Oral single loading dose 180ng<br>Drug: ASA<br>* 81mg once daily from day -2 up to platelet transfusion<br>|
| Experimental: 2<br>Ticagrelor without Platelet transfusion | Drug: Ticagrelor<br>* Oral single loading dose 180ng<br>Drug: ASA<br>* 81mg once daily from day -2 up to platelet transfusion<br>|
| Active Comparator: 3<br>Clopidogrel with Platelet transfusion | Drug: Clopidogrel<br>* Oral single loading dose 600mg<br>Drug: ASA<br>* 81mg once daily from day -2 up to platelet transfusion<br>|
| Active Comparator: 4<br>Clopidogrel without Platelet transfusion | Drug: Clopidogrel<br>* Oral single loading dose 600mg<br>Drug: ASA<br>* 81mg once daily from day -2 up to platelet transfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics in terms of percent of inhibition of adenosine phosphatase (ADP)-induced platelet aggregation assessed by light transmission aggregometry (LTA) after loading dose of Ticagrelor |  | Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics in terms of platelet reactivity as measured by P2Y12 Reaction Units (PRU) using VerifyNow™ after loading dose of Ticagrelor |  | Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h | 
| Pharmacodynamics in terms of platelet reactivity as measured by P2Y12 Reaction Units (PRU) using VerifyNow™ after loading dose of Clopidogrel |  | Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h | 
| Pharmacodynamics in terms of percent of inhibition of adenosine phosphatase (ADP)-induced platelet aggregation assessed by light transmission aggregometry (LTA) after loading dose of Clopidogrel |  | Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h | 
| Safety profile in terms of adverse events, blood pressure, pulse, temperature, ECG (Electrocardiogram), physical examination, and safety laboratory variables |  | up to 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1 Safety ,, pharmacodynamic,, Ticagrelor,, Clopidogrel,, Platelets