KF2019#1-trial: Effects of a Thrombocyte Inhibitor on a Cholesterol-lowering Drug

Study Overview
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Brief Summary
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The cholesterol-lowering drug rosuvastatin is a substrate of the breast cancer resistance protein (BCRP). BCRP is an efflux transporter expressed e.g. in the small intestine. It limits the oral bioavailability of rosuvastatin by transporting rosuvastatin from enterocytes back to the gut lumen. Inhibition of BCRP can increase rosuvastatin bioavailability and systemic concentrations. Ticagrelor is a platelet aggregation inhibitor used in treatment and prevention of atherothrombotic events. Ticagrelor may inhibit BCRP in humans. This study is aimed to investigate the possible interaction of rosuvastatin with ticagrelor. Ten healthy male or female non-smoking volunteers aged 18-40 years are taken into the study. Primary endpoint is area under the plasma concentration-time curve of rosuvastatin.

Official Title
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KF2019#1-tutkimus: Verihiutaleiden estäjän Vaikutus kolesterolilääkkeeseen

Conditions
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Pharmacokinetics

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age 18-40 Healthy Systolic blood pressure ≥100 mmHg Accepted results from laboratory tests (blood haemoglobin, basic blood count and blood platelets, alanine aminotransferase, alkaline phosphatase, glutamyl transferase, creatinine, plasma potassium and sodium). Negative pregnancy test result (serum human chorionic gonadotropin) for women. Fully vaccinated against COVID-19. Exclusion Criteria: Significant disease Abnormal result from the Helsinki University Hospital bleeding questionnaire Smoking Using oral contraception pills or other regular medication Pregnancy (current or planned) or nursing Participation in any other studies involving investigational or marketed drug products within three months prior to the entry into this study Donation of blood within three months prior to the entry into this study Significant overweight / small or hard-to-find veins Weight < 45 kg BMI < 18.5 kg/m2 Insufficient Finnish language skills

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The subjects will be given orally placebo twice a day for 2 days, and a single 10 mg dose of rosuvastatin. | Drug: Placebo<br>* one tablet of placebo twice daily for two days<br>Drug: Rosuvastatin<br>* 10 mg tablet, single dose<br>|
| Active Comparator: Ticagrelor<br>The subjects will be given orally 90 mg ticagrelor twice a day for 2 days, and a single 10 mg dose of rosuvastatin. | Drug: Ticagrelor<br>* Intervention Description: 90 mg tablet twice daily for two days<br>Drug: Rosuvastatin<br>* 10 mg tablet, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration - time curve of rosuvastatin |  | Prior to and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 23, and 47 hours after administration of rosuvastatin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration, half-life, time to peak plasma concentration, amount excreted, and renal clearance of rosuvastatin |  | Prior to and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 23, and 47 hours after administration of rosuvastatin |