Trial Outcomes & Findings for Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease (NCT NCT01107925)
NCT ID: NCT01107925
Last Updated: 2012-08-30
Results Overview
MPA to 20 micromolar (μM) ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
72 participants
Primary outcome timeframe
Baseline, Day 12
Results posted on
2012-08-30
Participant Flow
Participant milestones
| Measure |
5 mg Prasugrel (LBW)
During Study Period 1, participants received the 5-milligram (mg) prasugrel dose for 12 days without intervening or terminal washout periods. Participants in the low body weight (LBW; \<60 kilograms \[kg\]) treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2.
|
10 mg Prasugrel (LBW)
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
75 mg Clopidogrel (LBW)
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Period 1-Randomization up Through Day 12
STARTED
|
34
|
0
|
0
|
0
|
38
|
0
|
|
Period 1-Randomization up Through Day 12
Took at Least 1 Dose of Study Drug
|
34
|
0
|
0
|
0
|
38
|
0
|
|
Period 1-Randomization up Through Day 12
COMPLETED
|
33
|
0
|
0
|
0
|
37
|
0
|
|
Period 1-Randomization up Through Day 12
NOT COMPLETED
|
1
|
0
|
0
|
0
|
1
|
0
|
|
Period 2
STARTED
|
0
|
16
|
17
|
20
|
0
|
17
|
|
Period 2
Took at Least 1 Dose of Study Drug
|
0
|
16
|
17
|
20
|
0
|
17
|
|
Period 2
COMPLETED
|
0
|
15
|
17
|
20
|
0
|
16
|
|
Period 2
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
1
|
|
Period 3
STARTED
|
0
|
17
|
15
|
16
|
0
|
20
|
|
Period 3
Took at Least 1 Dose of Study Drug
|
0
|
17
|
15
|
16
|
0
|
20
|
|
Period 3
COMPLETED
|
0
|
17
|
15
|
16
|
0
|
20
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
5 mg Prasugrel (LBW)
During Study Period 1, participants received the 5-milligram (mg) prasugrel dose for 12 days without intervening or terminal washout periods. Participants in the low body weight (LBW; \<60 kilograms \[kg\]) treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2.
|
10 mg Prasugrel (LBW)
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
75 mg Clopidogrel (LBW)
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Period 1-Randomization up Through Day 12
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
1
|
0
|
|
Period 2
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease
Baseline characteristics by cohort
| Measure |
Dose Sequence: Pras 5mg, Pras 10mg, Clop 75mg (LBW)
n=17 Participants
Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received 5 milligrams (mg) of Prasugrel (Pras) during Study Period 1, followed by 10 mg Pras in Study Period 2, followed by 75 mg clopidogrel (Clop) in Study Period 3.
|
Dose Sequence: Pras 5mg, Clop 75 mg, Pras 10mg (LBW)
n=17 Participants
Participants in the LBW group received 5 mg Pras during Study Period 1, followed by 75 mg Clop in Study Period 2, and 10 mg Pras in Study Period 3.
|
Dose Sequence: Pras 10mg, Pras 5mg, Clop 75 mg (HBW)
n=21 Participants
Participants in the higher body weight (HBW; ≥60 kg) group received 10 mg Pras during Study Period 1, followed by 5 mg Pras in Study Period 2, followed by 75 mg Clop in Study Period 3.
|
Dose Sequence: Pras 10mg, Clop 75 mg, Pras 5mg (HBW)
n=17 Participants
Participants in the HBW group received 10 mg Pras during Study Period 1, followed by 5 mg Pras in Study Period 2, followed by 75 mg Clop in Study Period 3.
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
61.3 years
STANDARD_DEVIATION 8.07 • n=5 Participants
|
63.2 years
STANDARD_DEVIATION 7.65 • n=7 Participants
|
61.4 years
STANDARD_DEVIATION 9.57 • n=5 Participants
|
64.6 years
STANDARD_DEVIATION 6.91 • n=4 Participants
|
62.6 years
STANDARD_DEVIATION 8.15 • n=21 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
41 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
37 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
35 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
67 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
4 participants
n=21 Participants
|
|
Region of Enrollment
Ireland
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
8 participants
n=5 Participants
|
6 participants
n=4 Participants
|
18 participants
n=21 Participants
|
|
Region of Enrollment
Netherlands
|
9 participants
n=5 Participants
|
8 participants
n=7 Participants
|
5 participants
n=5 Participants
|
5 participants
n=4 Participants
|
27 participants
n=21 Participants
|
|
Region of Enrollment
Sweden
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
6 participants
n=5 Participants
|
4 participants
n=4 Participants
|
23 participants
n=21 Participants
|
|
Weight
|
56.06 kilograms (kg)
STANDARD_DEVIATION 4.575 • n=5 Participants
|
56.78 kilograms (kg)
STANDARD_DEVIATION 2.619 • n=7 Participants
|
83.60 kilograms (kg)
STANDARD_DEVIATION 17.146 • n=5 Participants
|
85.96 kilograms (kg)
STANDARD_DEVIATION 11.898 • n=4 Participants
|
71.33 kilograms (kg)
STANDARD_DEVIATION 17.980 • n=21 Participants
|
|
Tobacco Use Status
Tobacco Use Yes
|
7 participants
n=5 Participants
|
8 participants
n=7 Participants
|
5 participants
n=5 Participants
|
4 participants
n=4 Participants
|
24 participants
n=21 Participants
|
|
Tobacco Use Status
Tobacco Use No
|
10 participants
n=5 Participants
|
9 participants
n=7 Participants
|
16 participants
n=5 Participants
|
13 participants
n=4 Participants
|
48 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 12Population: Primary intent-to-treat (ITT) pharmacodynamic (PD) population: all randomized participants who continued in the study through Day 12, and had at least 1 evaluable PD assessment at Day 12. Participants were analyzed based on the treatment group they were randomized to irrespective to the treatment they received.
MPA to 20 micromolar (μM) ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.
Outcome measures
| Measure |
Prasugrel 5 mg (LBW)
n=33 Participants
Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received the 5-milligram (mg) prasugrel dose in Study Period 1.
|
Prasugrel 10 mg (HBW)
n=37 Participants
Participants in the higher body weight (HBW; ≥60 kg) group received the 10-mg prasugrel dose in Study Period 1.
|
75 mg Clopidogrel (LBW)
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 75-mg clopidogrel or 5-mg prasugrel dose either during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1)
Baseline
|
75.00 percent aggregation
Interval 70.0 to 80.0
|
76.40 percent aggregation
Interval 71.0 to 84.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1)
Day 12 (n=32, 37)
|
47.00 percent aggregation
Interval 37.7 to 56.45
|
47.00 percent aggregation
Interval 39.0 to 57.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 12Population: As-treated pharmacodynamic (PD) population: all randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable PD measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.
VASP phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition and were used to compare prasugrel versus clopidogrel, in low body weight (LBW) participants compared to higher body weight (HBW) participants. PRI was calculated by VASP. The PRI indicates the level of P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12 receptor thus stronger platelet inhibition, whereas a higher PRI reflects weaker inhibition of P2Y12 receptor and weaker platelet inhibition.
Outcome measures
| Measure |
Prasugrel 5 mg (LBW)
n=33 Participants
Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received the 5-milligram (mg) prasugrel dose in Study Period 1.
|
Prasugrel 10 mg (HBW)
n=32 Participants
Participants in the higher body weight (HBW; ≥60 kg) group received the 10-mg prasugrel dose in Study Period 1.
|
75 mg Clopidogrel (LBW)
n=32 Participants
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
n=36 Participants
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
n=37 Participants
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
n=36 Participants
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 75-mg clopidogrel or 5-mg prasugrel dose either during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy
Baseline
|
86.57 percentage PRI
Standard Deviation 4.44
|
86.44 percentage PRI
Standard Deviation 4.45
|
86.44 percentage PRI
Standard Deviation 4.45
|
86.77 percentage PRI
Standard Deviation 3.42
|
86.76 percentage PRI
Standard Deviation 3.37
|
86.77 percentage PRI
Standard Deviation 3.42
|
|
Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy
Day 12 (n=32,31,30,32,36,34)
|
33.54 percentage PRI
Standard Deviation 15.77
|
15.09 percentage PRI
Standard Deviation 11.71
|
39.01 percentage PRI
Standard Deviation 17.49
|
56.87 percentage PRI
Standard Deviation 15.47
|
27.79 percentage PRI
Standard Deviation 18.13
|
56.35 percentage PRI
Standard Deviation 18.33
|
SECONDARY outcome
Timeframe: Baseline, Day 12Population: As-treated pharmacodynamic (PD) population: all randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable PD measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.
The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in PRU. PRU indicates the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of rate and extent of platelet aggregation in an adenosine phosphate (ADP)-containing channel of the device. A lower PRU reflects stronger inhibition of platelet aggregation, whereas a higher PRU reflects weaker inhibition of platelet aggregation.
Outcome measures
| Measure |
Prasugrel 5 mg (LBW)
n=33 Participants
Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received the 5-milligram (mg) prasugrel dose in Study Period 1.
|
Prasugrel 10 mg (HBW)
n=32 Participants
Participants in the higher body weight (HBW; ≥60 kg) group received the 10-mg prasugrel dose in Study Period 1.
|
75 mg Clopidogrel (LBW)
n=32 Participants
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
n=36 Participants
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
n=37 Participants
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
n=36 Participants
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 75-mg clopidogrel or 5-mg prasugrel dose either during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy
Baseline
|
317.9 P2Y12 reaction units (PRU)
Standard Deviation 46.10
|
315.3 P2Y12 reaction units (PRU)
Standard Deviation 44.26
|
315.3 P2Y12 reaction units (PRU)
Standard Deviation 44.26
|
312.8 P2Y12 reaction units (PRU)
Standard Deviation 43.01
|
311.0 P2Y12 reaction units (PRU)
Standard Deviation 43.76
|
312.8 P2Y12 reaction units (PRU)
Standard Deviation 43.01
|
|
Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy
Day 12 (n=32,31,32,35,34,34)
|
129.5 P2Y12 reaction units (PRU)
Standard Deviation 62.14
|
55.9 P2Y12 reaction units (PRU)
Standard Deviation 38.08
|
151.7 P2Y12 reaction units (PRU)
Standard Deviation 57.46
|
193.9 P2Y12 reaction units (PRU)
Standard Deviation 74.09
|
102.1 P2Y12 reaction units (PRU)
Standard Deviation 69.49
|
207.0 P2Y12 reaction units (PRU)
Standard Deviation 67.62
|
SECONDARY outcome
Timeframe: baseline (pre-dose) up to 4 hours post-dosePopulation: All available PK sample data from all treated participants who contributed complete PK profiles.
A pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing MPA (LTA) and AUC was conducted as originally intended, however the graphic output is not possible here. Therefore, the PK portion is presented here as AUC and the PD portion is presented in Secondary Outcome Measure #5. AUC was calculated through the last scheduled sampling time of 4 hours \[AUC (0-4)\] or through the sampling time of the last quantifiable concentration prior to 4 hours. AUC values were denoted AUC(0-tlast) in both instances.
Outcome measures
| Measure |
Prasugrel 5 mg (LBW)
n=34 Participant Profiles
Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received the 5-milligram (mg) prasugrel dose in Study Period 1.
|
Prasugrel 10 mg (HBW)
n=50 Participant Profiles
Participants in the higher body weight (HBW; ≥60 kg) group received the 10-mg prasugrel dose in Study Period 1.
|
75 mg Clopidogrel (LBW)
n=45 Participant Profiles
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
n=52 Participant Profiles
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
n=38 Participant Profiles
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
n=57 Participant Profiles
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 75-mg clopidogrel or 5-mg prasugrel dose either during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC)
|
28.9 nanogram•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 37
|
59.3 nanogram•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 40
|
18.4 nanogram•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 38
|
19.4 nanogram•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 46
|
46.7 nanogram•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 44
|
12.7 nanogram•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 60
|
SECONDARY outcome
Timeframe: Baseline , Day 12Population: As-treated pharmacodynamic (PD) population: all randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable PD measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.
MPA to 20 micromolar (μM) adenosine diphosphate (ADP) was assessed by LTA, an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.
Outcome measures
| Measure |
Prasugrel 5 mg (LBW)
n=33 Participants
Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received the 5-milligram (mg) prasugrel dose in Study Period 1.
|
Prasugrel 10 mg (HBW)
n=32 Participants
Participants in the higher body weight (HBW; ≥60 kg) group received the 10-mg prasugrel dose in Study Period 1.
|
75 mg Clopidogrel (LBW)
n=32 Participants
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
n=36 Participants
Participants in the higher body weight (HBW; ≥ 60 kg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
n=37 Participants
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
n=36 Participants
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 75-mg clopidogrel or 5-mg prasugrel dose either during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy
Baseline
|
76.27 percent aggregation
Standard Deviation 9.49
|
76.20 percent aggregation
Standard Deviation 9.63
|
76.20 percent aggregation
Standard Deviation 9.63
|
77.63 percent aggregation
Standard Deviation 12.29
|
77.93 percent aggregation
Standard Deviation 12.27
|
77.63 percent aggregation
Standard Deviation 12.29
|
|
Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy
Day 12 ( n= 32,32,31,35,37,35)
|
48.10 percent aggregation
Standard Deviation 13.89
|
38.11 percent aggregation
Standard Deviation 14.17
|
51.41 percent aggregation
Standard Deviation 13.56
|
61.90 percent aggregation
Standard Deviation 18.93
|
47.92 percent aggregation
Standard Deviation 15.18
|
65.28 percent aggregation
Standard Deviation 17.83
|
Adverse Events
5 mg Prasugrel (LBW)
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
10 mg Prasugrel (LBW)
Serious events: 1 serious events
Other events: 21 other events
Deaths: 0 deaths
75 mg Clopidogrel (LBW)
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
5 mg Prasugrel (HBW)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
10 mg Prasugrel (HBW)
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
75 mg Clopidogrel (HBW)
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
5 mg Prasugrel (LBW)
n=34 participants at risk
During Study Period 1, participants received 5 milligrams (mg) prasugrel for 12 days without intervening or terminal washout periods. Participants in the low body weight (LBW; \<60 kilograms \[kg\]) treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2.
|
10 mg Prasugrel (LBW)
n=33 participants at risk
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
75 mg Clopidogrel (LBW)
n=32 participants at risk
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
n=36 participants at risk
Participants in the higher body weight (HBW; ≥ 60 mg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
n=38 participants at risk
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
n=37 participants at risk
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
Other adverse events
| Measure |
5 mg Prasugrel (LBW)
n=34 participants at risk
During Study Period 1, participants received 5 milligrams (mg) prasugrel for 12 days without intervening or terminal washout periods. Participants in the low body weight (LBW; \<60 kilograms \[kg\]) treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2.
|
10 mg Prasugrel (LBW)
n=33 participants at risk
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 10-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
75 mg Clopidogrel (LBW)
n=32 participants at risk
Participants in the LBW treatment sequence in Study Period 1 (5 mg prasugrel) were switched to either the 75-mg clopidogrel or 10-mg prasugrel dose during Study Period 2 or Study Period 3.
|
5 mg Prasugrel (HBW)
n=36 participants at risk
Participants in the higher body weight (HBW; ≥ 60 mg) treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
10 mg Prasugrel (HBW)
n=38 participants at risk
During Study Period 1, participants in the HBW treatment sequence received the 10-mg prasugrel dose for 12 days without intervening or terminal washout periods.
|
75 mg Clopidogrel (HBW)
n=37 participants at risk
Participants in the HBW treatment sequence in Study Period 1 (10 mg prasugrel) were switched to either the 5-mg prasugrel or 75-mg clopidogrel dose during Study Period 2 or Study Period 3.
|
|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
2/34 • Number of events 2
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Blood and lymphatic system disorders
Anaemia
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
0.00%
0/37
|
|
Blood and lymphatic system disorders
Macrocytosis
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Blood and lymphatic system disorders
Spontaneous haematoma
|
0.00%
0/34
|
3.0%
1/33 • Number of events 2
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
2.9%
1/34 • Number of events 2
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Gastrointestinal disorders
Haematochezia
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Gastrointestinal disorders
Nausea
|
5.9%
2/34 • Number of events 2
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
5.3%
2/38 • Number of events 3
|
5.4%
2/37 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
General disorders
Chest pain
|
2.9%
1/34 • Number of events 1
|
3.0%
1/33 • Number of events 1
|
3.1%
1/32 • Number of events 3
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
0.00%
0/37
|
|
General disorders
Fatigue
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
General disorders
Feeling abnormal
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
General disorders
Influenza like illness
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
0.00%
0/37
|
|
General disorders
Obstruction
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
General disorders
Pyrexia
|
5.9%
2/34 • Number of events 2
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Infections and infestations
Nasopharyngitis
|
8.8%
3/34 • Number of events 3
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Infections and infestations
Rhinitis
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Infections and infestations
Sinusitis
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Injury, poisoning and procedural complications
Contusion
|
17.6%
6/34 • Number of events 6
|
27.3%
9/33 • Number of events 9
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
7.9%
3/38 • Number of events 3
|
5.4%
2/37 • Number of events 2
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Injury, poisoning and procedural complications
Periorbital haematoma
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 1
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
2.9%
1/34 • Number of events 1
|
3.0%
1/33 • Number of events 1
|
6.2%
2/32 • Number of events 3
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
2.8%
1/36 • Number of events 2
|
0.00%
0/38
|
0.00%
0/37
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
0.00%
0/37
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Nervous system disorders
Dizziness
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 1
|
|
Nervous system disorders
Formication
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Nervous system disorders
Headache
|
0.00%
0/34
|
0.00%
0/33
|
3.1%
1/32 • Number of events 2
|
2.8%
1/36 • Number of events 1
|
5.3%
2/38 • Number of events 2
|
2.7%
1/37 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Nervous system disorders
Presyncope
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Respiratory, thoracic and mediastinal disorders
Chronic respiratory disease
|
2.9%
1/34 • Number of events 1
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.9%
1/34 • Number of events 2
|
6.1%
2/33 • Number of events 3
|
3.1%
1/32 • Number of events 1
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
5.4%
2/37 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
3.1%
1/32 • Number of events 1
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
|
Vascular disorders
Haematoma
|
8.8%
3/34 • Number of events 3
|
15.2%
5/33 • Number of events 7
|
9.4%
3/32 • Number of events 7
|
13.9%
5/36 • Number of events 7
|
7.9%
3/38 • Number of events 4
|
2.7%
1/37 • Number of events 3
|
|
Vascular disorders
Hypotension
|
0.00%
0/34
|
0.00%
0/33
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
2.7%
1/37 • Number of events 1
|
|
Vascular disorders
Intermittent claudication
|
0.00%
0/34
|
3.0%
1/33 • Number of events 1
|
0.00%
0/32
|
0.00%
0/36
|
0.00%
0/38
|
0.00%
0/37
|
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