The purpose of this study is to measure how much of the study drugs (clopidogrel and LY2216684) reach the blood stream and how long it takes the body to dispose of them and to determine how clopidogrel and LY2216684 might affect each other in the body. Information about any side effects that may occur will also be collected.
Clopidogrel is rapidly converted to R-130964 by the enzyme cytochrome P450 2C19 (CYP2C19). Enrollment in the study was limited to participants with specific genotypes of the CYP2C19 gene, including the \*1/\*1 genotype (CYP2C19 extensive metabolizers) and the \*1/\*17 or \*17/\*17 genotypes (CYP2C19 ultra-rapid metabolizers). All primary and secondary objectives were limited to participants with the CYP2C19\*1/\*1 genotype.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
47
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.
Dallas, Texas, United States
Pharmacokinetics of R-130964, Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684.
Time frame: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose
Pharmacokinetics of R-130964, Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-tlast)
R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684. Log-transformed AUC0-tlast was analyzed using a linear mixed effects model with sequence, period, and treatment as fixed effects and participant as a random effect.
Time frame: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose
Pharmacokinetics of R-130964, Maximum Observed Drug Concentrations (Cmax)
R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684. Log-transformed Cmax was analyzed using a linear mixed effects model with sequence, period, and treatment as fixed effects and participant as a random effect.
Time frame: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose
Pharmacokinetics of R-130964, Time to Maximum Observed Drug Concentrations (Tmax)
R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684.
Time frame: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose
Percentage Inhibition of Platelet Aggregation
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Blood samples for the measurement of platelet aggregation using a point-of-care device, Accumetrics VerifyNow™ P2Y12 (VN-P2Y12), were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684. Device-reported percent inhibition of VN-P2Y12 (IPRU) is presented.
Time frame: predose and 2, 4, and 24 hours postdose