Study of Prasugrel in Korean Healthy Male Volunteers

Single and Multiple Dose Pharmacokinetics and Pharmacodynamics of Prasugrel (LY640315) in Korean Healthy Male Subjects

The purpose of this study is to investigate how the body processes prasugrel and how prasugrel affects blood clotting in healthy Korean men. Three different dosing regimens of prasugrel will be given. Information on side effects will also be collected.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Prasugrel

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Are overtly healthy males, as determined by medical history and physical examination.
• Are between the ages of 20 and 45 years, inclusive.
• Have a body mass index (BMI) of 19 kg/m^2 to 27 kg/m^2, inclusive, at screening.

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 60 days from a clinical trial involving an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have known allergies to prasugrel or related compounds.
• Are persons who have previously completed or withdrawn from this study or any other study investigating prasugrel.
• Self-reported history of significant bleeding from trauma (for example, prolonged bleeding after tooth extraction).
• History of major surgery within 3 months of screening or planned surgery within 14 days after the last day of dosing.
• Have a platelet count of <100,000/(cubic millimeters) mm^3 at the time of screening.
• Have tested positive for fecal occult blood at screening.
• Have significant prolongation of prothrombin time (PT) or activated partial thromboplastin time (APTT) at screening.
• Have a clinically significant abnormality following the investigator's review of the physical examination, electrocardiogram (ECG)and clinical (safety) laboratory tests at screening.
• Personal or first-degree family history of coagulation or bleeding disorders (that is, hematemesis, melena, severe or recurrent epistaxis, hemoptysis, gastrointestinal ulcers, hemorrhage, clinically overt hematuria or intracranial hemorrhage) or reasonable suspicion of vascular malformations, for example, cerebral hemorrhage, aneurysm or premature stroke (cerebrovascular accident [CVA] <65 years of age).
• Have significant active hematological disease and/or whole blood donation of more than 400 mL within the last 2 months and component blood donation within the last month.
• Volunteers who have an average weekly alcohol intake that exceeds 21 units per week or volunteers unwilling to adhere to study alcohol restrictions during the study (1 unit = 360 mL of beer; 150 mL of wine; 45 mL of distilled spirits).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel - 60 mg/10 mg; Prasugrel 60 mg loading dose given once orally, followed by 10 mg once a day orally for 10 days	Drug: Prasugrel; Tablets orally; Other Names: Effient; LY640315; Efient; Prasita
Experimental: Prasugrel - 30 mg/7.5 mg; Prasugrel 30 mg loading dose given once orally, followed by 7.5 mg once a day orally for 10 days	Drug: Prasugrel; Tablets orally; Other Names: Effient; LY640315; Efient; Prasita
Experimental: Prasugrel - 30 mg/5 mg; Prasugrel 30 mg loading dose given once orally followed by 5 mg once a day orally for 10 days	Drug: Prasugrel; Tablets orally; Other Names: Effient; LY640315; Efient; Prasita

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Prasugrel's Active Metabolite R-138727 During Loading Dose	AUC from time zero to the last quantifiable plasma concentration (tlast)	Day 1 predose up to 24 hours post dose
Pharmacokinetics (PK): Maximum Concentration (Cmax) for Prasugrel's Active Metabolite R-138727 During Loading Dose		Day 1 predose up to 24 hours post dose
Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of Prasugrel's Active Metabolite R-138727 During Loading Dose		Day 1 predose up to 24 hours post dose
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Prasugrel's Active Metabolite R-138727 During Maintenance Dose	AUC from time zero to the last quantifiable plasma concentration (tlast)	Day 11 predose to 24 hours post dose
Pharmacokinetics (PK): Maximum Concentration (Cmax) for Prasugrel's Active Metabolite R-138727 During Maintenance Dose		Day 11 predose to 24 hours post dose
Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of Prasugrel's Active Metabolite R-138727 During Maintenance Dose		Day 11 predose to 24 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-mediated Platelet Aggregation	ADP-induced PRU represents the rate and extent of ADP-stimulated platelet aggregation and serves as a biomarker of clinical efficacy, with lower values indicating greater P2Y12 platelet inhibition	Predose up to 24 hours post dose on Day 12
Percent Inhibition of Verify Now (VN)-P2Y12 Reaction Units (PRU)	PRU device reported VerifyNow percent inhibition is reported by Accumetrics VerifyNow™ P2Y12 (VN-P2Y12) assay, a point-of-care device that measures platelet aggregation with single-use, disposable cartridges	Predose up to 24 hours post dose on Day 12

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Yu KS, Park KW, Kelly RP, Gu N, Payne C, Small DS, Choi HC, Kawakatsu E, Pinton P. Pharmacokinetic and pharmacodynamic effects of prasugrel in healthy Korean males. J Cardiovasc Pharmacol. 2013 Jul;62(1):72-7. doi: 10.1097/FJC.0b013e318290d9e1.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: May 2, 2012
• First Submitted That Met QC Criteria: May 2, 2012
• First Posted (Estimate): May 4, 2012

Study Record Updates

• Last Update Posted (Estimate): October 4, 2012
• Last Update Submitted That Met QC Criteria: September 4, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Platelet Aggregation Inhibitors; Prasugrel Hydrochloride
• Other Study ID Numbers: 11990; H7T-FW-TACQ (Other Identifier: Eli Lilly and Company)