Trial Outcomes & Findings for A Pharmacokinetic Study on the Effect of LY2216684 on the Active Metabolite of Clopidogrel (NCT NCT01263093)
NCT ID: NCT01263093
Last Updated: 2018-10-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
47 participants
Primary outcome timeframe
predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose
Results posted on
2018-10-22
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1
STARTED
|
24
|
23
|
|
Period 1
COMPLETED
|
24
|
23
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Washout
STARTED
|
24
|
23
|
|
Washout
COMPLETED
|
23
|
23
|
|
Washout
NOT COMPLETED
|
1
|
0
|
|
Period 2
STARTED
|
23
|
23
|
|
Period 2
COMPLETED
|
22
|
23
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Washout
Physician Decision
|
1
|
0
|
|
Period 2
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Pharmacokinetic Study on the Effect of LY2216684 on the Active Metabolite of Clopidogrel
Baseline characteristics by cohort
| Measure |
Clopidogrel First, Then LY2216684 + Clopidogrel
n=24 Participants
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
n=23 Participants
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.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.7 years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
44.5 years
STANDARD_DEVIATION 11.5 • n=7 Participants
|
42.5 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdosePopulation: 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.
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.
Outcome measures
| Measure |
Clopidogrel
n=31 Participants
Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1 of Treatment 1
|
LY2216684 + Clopidogrel
n=15 Participants
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
|
|---|---|---|
|
Pharmacokinetics of R-130964, Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
|
61.8 hours*nanograms/milliliters (h*ng/mL)
Geometric Coefficient of Variation 50
|
55.3 hours*nanograms/milliliters (h*ng/mL)
Geometric Coefficient of Variation 44
|
PRIMARY outcome
Timeframe: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdosePopulation: Participants with the CYP2C19\*1/\*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data.
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.
Outcome measures
| Measure |
Clopidogrel
n=38 Participants
Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1 of Treatment 1
|
LY2216684 + Clopidogrel
n=36 Participants
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
|
|---|---|---|
|
Pharmacokinetics of R-130964, Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-tlast)
|
60.5 hours*nanograms/milliliters (h*ng/mL)
Geometric Coefficient of Variation 45
|
46.9 hours*nanograms/milliliters (h*ng/mL)
Geometric Coefficient of Variation 41
|
PRIMARY outcome
Timeframe: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdosePopulation: Participants with the CYP2C19\*1/\*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data.
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.
Outcome measures
| Measure |
Clopidogrel
n=38 Participants
Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1 of Treatment 1
|
LY2216684 + Clopidogrel
n=36 Participants
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
|
|---|---|---|
|
Pharmacokinetics of R-130964, Maximum Observed Drug Concentrations (Cmax)
|
37.6 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 56
|
22.7 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 53
|
PRIMARY outcome
Timeframe: predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdosePopulation: Participants with the CYP2C19\*1/\*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable R-130964 plasma concentration data.
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.
Outcome measures
| Measure |
Clopidogrel
n=36 Participants
Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1 of Treatment 1
|
LY2216684 + Clopidogrel
n=36 Participants
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
|
|---|---|---|
|
Pharmacokinetics of R-130964, Time to Maximum Observed Drug Concentrations (Tmax)
|
1.50 hours
Interval 1.0 to 2.07
|
1.50 hours
Interval 0.5 to 4.0
|
SECONDARY outcome
Timeframe: predose and 2, 4, and 24 hours postdosePopulation: Participants with the CYP2C19\*1/\*1 genotype, who received at least 1 dose of clopidogrel, and had evaluable IPRU data.
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.
Outcome measures
| Measure |
Clopidogrel
n=38 Participants
Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1 of Treatment 1
|
LY2216684 + Clopidogrel
n=37 Participants
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
|
|---|---|---|
|
Percentage Inhibition of Platelet Aggregation
24 Hours Postdose
|
25.1 IPRU
Standard Deviation 21.1
|
14.3 IPRU
Standard Deviation 17.5
|
|
Percentage Inhibition of Platelet Aggregation
Predose
|
1.7 IPRU
Standard Deviation 3.2
|
1.4 IPRU
Standard Deviation 3.2
|
|
Percentage Inhibition of Platelet Aggregation
2 Hours Postdose
|
16.0 IPRU
Standard Deviation 20.3
|
7.6 IPRU
Standard Deviation 12.3
|
|
Percentage Inhibition of Platelet Aggregation
4 Hours Postdose
|
30.4 IPRU
Standard Deviation 21.8
|
14.0 IPRU
Standard Deviation 16.6
|
Adverse Events
Clopidogrel
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
LY2216684
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
LY2216684 + Clopidogrel
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Clopidogrel
n=47 participants at risk
Clopidogrel: a single 300-milligram (mg) dose, administered orally on Day 1
Time Frame: Treatment 1
|
LY2216684
n=46 participants at risk
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
|
LY2216684 + Clopidogrel
n=45 participants at risk
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
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/47
|
6.5%
3/46 • Number of events 4
|
0.00%
0/45
|
|
Gastrointestinal disorders
Nausea
|
2.1%
1/47 • Number of events 1
|
15.2%
7/46 • Number of events 8
|
4.4%
2/45 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/47
|
6.5%
3/46 • Number of events 3
|
0.00%
0/45
|
|
General disorders
Chills
|
4.3%
2/47 • Number of events 2
|
2.2%
1/46 • Number of events 1
|
4.4%
2/45 • Number of events 2
|
|
General disorders
Pain
|
4.3%
2/47 • Number of events 2
|
0.00%
0/46
|
2.2%
1/45 • Number of events 1
|
|
General disorders
Pyrexia
|
2.1%
1/47 • Number of events 1
|
0.00%
0/46
|
4.4%
2/45 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/47
|
4.3%
2/46 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Headache
|
12.8%
6/47 • Number of events 6
|
2.2%
1/46 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/47
|
4.3%
2/46 • Number of events 2
|
2.2%
1/45 • Number of events 3
|
|
Nervous system disorders
Somnolence
|
0.00%
0/47
|
15.2%
7/46 • Number of events 7
|
0.00%
0/45
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/47
|
6.5%
3/46 • Number of events 3
|
6.7%
3/45 • Number of events 3
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/47
|
4.3%
2/46 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Renal and urinary disorders
Urinary hesitation
|
0.00%
0/47
|
8.7%
4/46 • Number of events 6
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.4%
3/47 • Number of events 3
|
0.00%
0/46
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/47
|
4.3%
2/46 • Number of events 3
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/47
|
2.2%
1/46 • Number of events 2
|
6.7%
3/45 • Number of events 4
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60