The Effect of Ticagrelor With or Without Atorvastatin on Endothelial Function in Healthy Males

Study Overview
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Brief Summary
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To test the effect of atorvastatin or placebo in combination with ticagrelor on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by forearm blood flow (FBF) measurement before and 10 min after a 20 min forearm ischemia. The area under the dose-effect curve (AUC) of different ACh doses will be calculated and compared between treatment groups (atorvastatin + ticagrelor vs. placebo + ticagrelor) and different time points (pre-ischemia vs. post-ischemia).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Effect of Atorvastatin Treatment for 14 Days in Combination With an Acute Dose of Ticagrelor on Ischemia Reperfusion Induced Endothelial Dysfunction of the Forearm Vasculature in Healthy Male Subjects

Conditions
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Ischemia

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects; 18 - 40 years of age Body mass index between 18 and 27 kg/m2 Written informed consent Normal findings in medical & bleeding history Non-smoking Exclusion Criteria: Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease) Known disorders with increased bleeding risk (e.g. peridontosis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer) Known sensitivity to common causes of bleeding (e.g. nasal) History of thromboembolism History of occlusive vascular diseases History of vascular anomalies History of hypercholesterolemia History of myopathy Impaired liver function (AST, ALT, gGT, bilirubin > 3 x ULN) Impaired renal function (serum creatinine > 1.3 mg/dl) Elevated creatinine-kinase or serum-myoglobin (> 3 x ULN) Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis HIV-1/2-Ab, HbsAg or HCV-Ab positive serology Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg Known allergy against any test agent under study Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol Participation in another clinical trial during the preceding 3 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>80 mg atorvastatin for 14 days with a loading dose of 180 mg ticagrelor on day 15 | Drug: Atorvastatin<br>* Subjects will receive 80 mg atorvastatin once daily for 14 days (until study day 15). On study day 15, 80 mg atorvastatin in combination with a loading dose of 180 mg ticagrelor will be administered.<br>Drug: Ticagrelor<br> <br> |
| Placebo Comparator: Placebo<br>Placebo for 14 days with a loading dose of 180 mg ticagrelor on day 15 | Drug: Placebo<br>* Subjects will receive placebo once daily for 14 days (until study day 15). On study day 15, placebo in combination with a loading dose of 180 mg ticagrelor will be administered.<br>Drug: Ticagrelor<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholine (ACh) induced vasodilatation | To test the effect of atorvastatin or placebo in combination with ticagrelor on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia | Change of the AUC before and 10 min after forearm ischemia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceryltrinitrate (GTN) induced vasodilatation | To test the effect of atorvastatin or placebo in combination with ticagrelor on GTN-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia | Change of the AUC before and 10 min after forearm ischemia |