PKPD Study of Ticagrelor and Prasugrel in Healthy Korean Males

A Single Dose, Open-label, One Sequence, 2-period, Crossover Study to Characterize the Pharmacokinetics and Pharmacodynamics of Ticagrelor and Prasugrel in Healthy Male Adult Subjects

This study is to characterize the pharmacokinetic and pharmacodynamics of ticagrelor and prasugrel in healthy Korean male subjects.

The study is open label, one sequence, crossover design. In period 1, a single oral dose of 180 mg ticagrelor will be administrated. After at least 7 days washout period, in period 2, a single oral dose of 60 mg prasugrel will be administrated.

After dosing each period, blood sampling for PK and PD assessment will be conducted.

1. Blood Sampling Times

   1. PK :predose,10 min,15 min,25 min, 0.5,1,1.5,2,2.5,4,6,8,12 and 24h post-dose
   2. PD :predose,15 min,0.5,1,2,4,6,8,12 and 24h post-dose

2. Bioanalysis

   1. plasma Ticagrelor
   2. plasma AR-C124910XX (active metabolite of ticagrelor)
   3. plasma R-95913 (inactive metabolite of prasugrel)
   4. plasma R-13727 (active metabolite of prasugrel)
3. Platelet Aggregation Test using turbidometric Method Maximal Platelet Aggregation(MPA)
4. PK-PD Modeling analysis

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ticagrelor/prasugrel

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. male aged 19 - 45 years at screening visit
2. body weight at least 60 kg at screening visit
3. body mass index 18 - 30 kg/m2
4. SBP 90 - 149 mmHg and DBP 60 - 99 mmHg and pulse rate(beat per minute) 45 - 100 at screening visit

Exclusion Criteria:

1. any history of or having any clinically significant abnormalities
2. any gastrointestinal disorder having impact on absorption of study drug
3. any history of hypersensitivity of ticagrelor or prasugrel or compounds related study drugs
4. any history of taking original medicines within 30 days before dosing or history of taking prescribed drug within 14 days before dosing or history of taking OTC drug within 7 days before dosing
5. any history of taking other study drug within 60 days before dosing
6. any history of whole blood transfusion within 60 days before dosing or history of blood elements transfusion or history of heaving been transfused within 30 days before 30 days
7. any history of taking metabolic inducer or inhibitor
8. overuse (caffeine: > 5 units/day , alcohol: > 21 units /week, smoking: > 10 cigarettes/day)
9. positive serology testy(Hbs antigen, HIV, Hepatitis C virus, Syphilis)
10. any abnormality in clinical laboratory tests result or any ECG finding considered to be inadequate by investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ticagrelor-prasugrel; in period 1, 180 mg of ticagrelor will be administrated at a single oral dose. in period 2, 60 mg of prasugrel will be administrated at a single oral dose.	Drug: ticagrelor/prasugrel; Other Names: ticagrelor :2 tablets of Brilinta® 90 mg; prasugrel : 6 tablets of Effient® 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma ticagrelor parent,AR-C124910XX,R-95913 and R-13727	4 mL of blood will be drawn per each collection	0,10 min,15 min,25 min,0.5h,1h,1.5h,2h,2.5h,4h,6h,8h,12h and 24h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Platelet Aggregation(MPA)	platelet aggregation will be tested using light transmission aggregometry	0,15 min,0.5 min, 1h,2h,4h,8h and 24h

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event monitoring	all adverse event will be collected	up to 1 week

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Hyeong-Seok Lim, Professor, Asan Medical Center

Publications and helpful links

General Publications

• Jeon HS, Kim MJ, Choi HY, Kim YH, Kim EH, Kim AR, Park HJ, Bae KS, Lim HS. Pharmacokinetics and pharmacodynamics of ticagrelor and prasugrel in healthy male Korean volunteers. Clin Ther. 2015 Mar 1;37(3):563-73. doi: 10.1016/j.clinthera.2015.01.010. Epub 2015 Feb 16. Erratum In: Clin Ther. 2015 Sep 1;37(9):2149.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: June 10, 2013
• First Submitted That Met QC Criteria: June 11, 2013
• First Posted (Estimate): June 13, 2013

Study Record Updates

• Last Update Posted (Estimate): March 3, 2014
• Last Update Submitted That Met QC Criteria: February 27, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: Hyeong-Seok Lim