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| ID | Type | Description | Link |
|---|---|---|---|
| H9P-EW-LNBY | Other Identifier | Eli Lilly and Company |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clopidogrel First, Then LY2216684 + Clopidogrel | Experimental | Period 1: a single 300-milligram (mg) dose of clopidogrel administered orally on Day 1 (Treatment 1). Period 2: an 18-mg dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2. |
|
| LY2216684 + Clopidogrel First, Then Clopidogrel | Experimental | Period 1: an 18-milligram (mg) dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). Period 2: a single 300-mg dose of clopidogrel administered orally on Day 1 (Treatment 1). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug |
| ||
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Inhibition of Platelet Aggregation | 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. | predose and 2, 4, and 24 hours postdose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Clopidogrel First, Then LY2216684 + Clopidogrel | Period 1: a single 300-milligram (mg) dose of clopidogrel administered orally on Day 1 (Treatment 1). Period 2: an 18-mg dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2. |
| FG001 | LY2216684 + Clopidogrel First, Then Clopidogrel | Period 1: an 18-milligram (mg) dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). Period 2: a single 300-mg dose of clopidogrel administered orally on Day 1 (Treatment 1). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Washout |
| |||||||||||||
| Period 2 |
|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Clopidogrel First, Then LY2216684 + Clopidogrel | Period 1: a single 300-milligram (mg) dose of clopidogrel administered orally on Day 1 (Treatment 1). Period 2: an 18-mg dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Participants with the CYP2C19*1/*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data, including sufficient data in the terminal elimination phase for R-130964. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanograms/milliliters (h*ng/mL) | predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Clopidogrel | Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1 Time Frame: Treatment 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| C568831 | alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
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| LY2216684 |
| Drug |
|
| United States |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
|
| BG001 | LY2216684 + Clopidogrel First, Then Clopidogrel | Period 1: an 18-milligram (mg) dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). Period 2: a single 300-mg dose of clopidogrel administered orally on Day 1 (Treatment 1). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 |
| LY2216684 + Clopidogrel |
LY2216684: 18-milligram (mg) dose, administered orally, once daily (QD) on Days 1 through 3 of Treatment 2 Clopidogrel: a single 300-mg dose, administered orally on Day 3 of Treatment 2 |
|
|
| Primary | 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. | Participants with the CYP2C19*1/*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanograms/milliliters (h*ng/mL) | predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose |
|
|
|
|
| Primary | 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. | Participants with the CYP2C19*1/*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms/milliliter (ng/mL) | predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose |
|
|
|
|
| Secondary | Percentage Inhibition of Platelet Aggregation | 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. | Participants with the CYP2C19*1/*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable IPRU data. | Posted | Mean | Standard Deviation | IPRU | predose and 2, 4, and 24 hours postdose |
|
|
|
| Primary | 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. | Participants with the CYP2C19*1/*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data. | Posted | Median | Full Range | hours | predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose |
|
|
|
|
| 0 |
| 47 |
| 12 |
| 47 |
| EG001 | LY2216684 | LY2216684: 18-milligram (mg) dose, administered orally, once daily (QD) on Days 1 through 3 Time Frame: Treatment 2; prior to clopidogrel dose on Day 3 | 0 | 46 | 19 | 46 |
| EG002 | LY2216684 + Clopidogrel | LY2216684: 18-milligram (mg) dose, administered orally, once daily (QD) on Days 1 through 3 Clopidogrel: a single 300-mg dose, administered orally on Day 3 Time Frame: Treatment 2; after the clopidogrel dose on Day 3 | 0 | 45 | 11 | 45 |
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
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| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| 4 Hours Postdose |
|
| 24 Hours Postdose |
|