Trial Outcomes & Findings for A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease (NCT NCT01476696)
NCT ID: NCT01476696
Last Updated: 2014-02-13
Results Overview
AUC of Pras-AM from time 0 up to the last sampling time of 4 hours postdose \[AUC(0-tlast)\] is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and is reported for doses administered on site (0.06, 0.08, and 0.12 mg/kg) during Part B (once-daily repeated dosing phase) of the study. Four participants received the same dose at multiple visits where pharmacokinetic samples were collected.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose
Results posted on
2014-02-13
Participant Flow
The study was conducted in 2 parts: Part A (single-dose range finding phase) then Part B (once-daily repeated dosing phase). Participants completing Part A could, but were not required to, participate in Part B. There were 2 dosing periods during Part B of the study.
Participant milestones
| Measure |
Part A: Prasugrel Single Dose
Participants who only enrolled in Part A of the study.
Part A: 0.03 milligrams per kilogram (mg/kg) up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally \[oral-disintegrating tablet (ODT)\] up to 3 times, at different mg/kg doses, with up to 18 days between doses.
|
Part B: Prasugrel Once-Daily Dose
Participants who only enrolled in Part B of the study.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel, administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.
|
Part A Then Part B: Prasugrel Single Dose Then Once-Daily Dose
Participants who enrolled in Part A and B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition.
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
9
|
9
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
15
|
9
|
9
|
|
Overall Study
COMPLETED
|
12
|
8
|
9
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
0
|
Reasons for withdrawal
| Measure |
Part A: Prasugrel Single Dose
Participants who only enrolled in Part A of the study.
Part A: 0.03 milligrams per kilogram (mg/kg) up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally \[oral-disintegrating tablet (ODT)\] up to 3 times, at different mg/kg doses, with up to 18 days between doses.
|
Part B: Prasugrel Once-Daily Dose
Participants who only enrolled in Part B of the study.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel, administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.
|
Part A Then Part B: Prasugrel Single Dose Then Once-Daily Dose
Participants who enrolled in Part A and B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition.
|
|---|---|---|---|
|
Overall Study
Sponsor decision
|
2
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=33 Participants
Participants enrolled in Part A, Part A and B, or only Part B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, so that the second dose would be unlikely to exceed 50% platelet inhibition.
|
|---|---|
|
Age, Customized
≥2 and ≤5 years
|
7 participants
n=99 Participants
|
|
Age, Customized
≥6 and ≤11 years
|
14 participants
n=99 Participants
|
|
Age, Customized
≥12 and ≤17 years
|
12 participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
32 participants
n=99 Participants
|
|
Region of Enrollment
United States
|
33 participants
n=99 Participants
|
|
Height
|
139.21 centimeters (cm)
STANDARD_DEVIATION 22.663 • n=99 Participants
|
|
Weight
|
38.55 kilograms (kg)
STANDARD_DEVIATION 18.785 • n=99 Participants
|
|
Body Mass Index
|
18.64 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.091 • n=99 Participants
|
|
Genotype
HbSS
|
30 participants
n=99 Participants
|
|
Genotype
HbS Beta^0 Thalassemia
|
3 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdosePopulation: Participants who received at least 1 dose of prasugrel.
AUC of Pras-AM from time 0 up to the last sampling time of 4 hours postdose \[AUC(0-tlast)\] is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and is reported for doses administered on site (0.06, 0.08, and 0.12 mg/kg) during Part B (once-daily repeated dosing phase) of the study. Four participants received the same dose at multiple visits where pharmacokinetic samples were collected.
Outcome measures
| Measure |
Entire Study Population
n=33 Participants
Participants enrolled in Part A, Part A and B, or only Part B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, so that the second dose would be unlikely to exceed 50% platelet inhibition.
|
Part B: Prasugrel Once-Daily Dose (0.06 mg/kg)
Participants who received 0.06 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.08 mg/kg)
Participants who received 0.08 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.12 mg/kg)
Participants who received 0.12 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.03 mg/kg (n=2)
|
8.68 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 36
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.05 mg/kg (n=2)
|
14.5 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 44
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.07 mg/kg (n=2)
|
20.8 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 31
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.09 mg/kg (n=2)
|
31.3 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 25
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.11 mg/kg (n=1)
|
22.2 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation NA
The geometric coefficient of variation could not be determined because data for only 1 profile were analyzed.
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.13 mg/kg (n=2)
|
50.3 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 20
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.15 mg/kg (n=2)
|
35.2 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 86
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.2 mg/kg (n=2)
|
43.7 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 48
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.25 mg/kg (n=3)
|
60.7 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 88
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.3 mg/kg (n=6)
|
87.9 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 52
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.35 mg/kg (n=11)
|
111 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 59
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.4 mg/kg (n=14)
|
108 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 55
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.45 mg/kg (n=8)
|
136 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 53
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.5 mg/kg (n=7)
|
186 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 36
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.55 mg/kg (n=1)
|
87.0 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation NA
The geometric coefficient of variation could not be determined because data for only 1 profile were analyzed.
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part A: 0.6 mg/kg (n=3)
|
299 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 4
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part B: 0.06 mg/kg (n=7)
|
16.3 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 50
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part B: 0.08 mg/kg (n=17)
|
27.1 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 20
|
—
|
—
|
—
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Part B: 0.12 mg/kg (n=8)
|
38.5 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 15
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage)Population: Participants who received at least 1 dose of prasugrel.
Accumetrics VN assay: A point-of-care device that measures platelet aggregation. Percentage of platelet inhibition is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and also during the once-daily repeated dosing phase in Part B, at steady state, 14 ± 4 days after each new dose (0.06, 0.08, and 0.12 mg/kg) is administered. One participant received the same dose at multiple visits (Part A) and one participant received the same daily dose during both dosing periods in Part B.
Outcome measures
| Measure |
Entire Study Population
n=33 Participants
Participants enrolled in Part A, Part A and B, or only Part B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, so that the second dose would be unlikely to exceed 50% platelet inhibition.
|
Part B: Prasugrel Once-Daily Dose (0.06 mg/kg)
Participants who received 0.06 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.08 mg/kg)
Participants who received 0.08 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.12 mg/kg)
Participants who received 0.12 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
|---|---|---|---|---|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.03 mg/kg (n=2)
|
2.0 percentage of platelet inhibition
Standard Deviation 2.83
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.05 mg/kg (n=2)
|
0.0 percentage of platelet inhibition
Standard Deviation 0.00
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.07 mg/kg (n=2)
|
0.0 percentage of platelet inhibition
Standard Deviation 0.00
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.08 mg/kg (n=18)
|
7.7 percentage of platelet inhibition
Standard Deviation 9.35
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.09 mg/kg (n=2)
|
2.5 percentage of platelet inhibition
Standard Deviation 3.54
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.11 mg/kg (n=1)
|
0.0 percentage of platelet inhibition
Standard Deviation NA
Could not be determined because data for only 1 participant were analyzed.
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.13 mg/kg (n=2)
|
9.5 percentage of platelet inhibition
Standard Deviation 13.44
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.15 mg/kg (n=2)
|
4.0 percentage of platelet inhibition
Standard Deviation 0.00
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.2 mg/kg (n=2)
|
0.0 percentage of platelet inhibition
Standard Deviation 0.00
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.25 mg/kg (n=3)
|
18.0 percentage of platelet inhibition
Standard Deviation 18.52
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.3 mg/kg (n=6)
|
42.3 percentage of platelet inhibition
Standard Deviation 27.21
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.35 mg/kg (n=11)
|
38.0 percentage of platelet inhibition
Standard Deviation 28.46
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.4 mg/kg (n=14)
|
39.1 percentage of platelet inhibition
Standard Deviation 26.77
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.45 mg/kg (n=8)
|
35.3 percentage of platelet inhibition
Standard Deviation 27.16
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.5 mg/kg (n=7)
|
55.9 percentage of platelet inhibition
Standard Deviation 27.85
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.55 mg/kg (n=1)
|
31.0 percentage of platelet inhibition
Standard Deviation NA
Could not be determined because data for only 1 participant were analyzed.
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part A: 0.6 mg/kg (n=3)
|
70.3 percentage of platelet inhibition
Standard Deviation 19.22
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part B: 0.06 mg/kg (n=8)
|
38.6 percentage of platelet inhibition
Standard Deviation 21.07
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part B: 0.08 mg/kg (n=18)
|
37.8 percentage of platelet inhibition
Standard Deviation 25.86
|
—
|
—
|
—
|
|
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Part B: 0.12 mg/kg (n=8)
|
48.1 percentage of platelet inhibition
Standard Deviation 11.29
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Part A: 0.5, 1, 1.5, 2, 4 hours postdosePopulation: No participants were analyzed.
AUC of prasugrel inactive metabolite(s) from time 0 up to the last sampling time of 4 hours postdose \[AUC(0-tlast)\]. Improvements in bioanalytical methodology enabled direct measurement of Pras-AM from plasma, obviating the need to estimate its concentration from inactive downstream metabolite(s). Thus, the AUC of prasugrel inactive metabolite(s) was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Part B: Baseline and Day14 ± 4 days postdose in each dosing periodPopulation: Participants who responded to Question 1 of the SCD Questionnaire. A participant could be counted more than once because there were 2 dosing periods during Part B of the study.
The number of participants who answered "yes" to the first question in the Sickle Cell Disease Pain (SCD) Questionnaire is reported. Question 1: In the past 2 weeks, did you experience any sickle cell pain?
Outcome measures
| Measure |
Entire Study Population
n=18 Participants
Participants enrolled in Part A, Part A and B, or only Part B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, so that the second dose would be unlikely to exceed 50% platelet inhibition.
|
Part B: Prasugrel Once-Daily Dose (0.06 mg/kg)
n=9 Participants
Participants who received 0.06 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.08 mg/kg)
n=17 Participants
Participants who received 0.08 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.12 mg/kg)
n=8 Participants
Participants who received 0.12 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
|---|---|---|---|---|
|
Number of Participants With Pain
|
6 participants
|
4 participants
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Part B: Baseline up to Day 36Population: Participants who received at least 1 dose of prasugrel.
Hemorrhagic events were determined by the study investigator. Medical intervention was defined as any medical attention resulting in therapy or further investigation, as determined by a trained medical professional.
Outcome measures
| Measure |
Entire Study Population
n=18 Participants
Participants enrolled in Part A, Part A and B, or only Part B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, so that the second dose would be unlikely to exceed 50% platelet inhibition.
|
Part B: Prasugrel Once-Daily Dose (0.06 mg/kg)
Participants who received 0.06 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.08 mg/kg)
Participants who received 0.08 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
Part B: Prasugrel Once-Daily Dose (0.12 mg/kg)
Participants who received 0.12 mg/kg Prasugrel administered orally, ODT, once daily, anytime (first or second dosing period) during Part B of the study, for a total of up to 36 days.
|
|---|---|---|---|---|
|
Number of Participants With Hemorrhagic Events Requiring Medical Intervention
|
0 participants
|
—
|
—
|
—
|
Adverse Events
Part A: Prasugrel Single Dose
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Part B: Prasugrel Once-Daily Dose
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Part A and Part B Participants: During Part A
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Part A and Part B Participants: During Part B
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A: Prasugrel Single Dose
n=15 participants at risk
Participants who only enrolled in Part A of the study.
Part A: 0.03 milligrams per kilogram (mg/kg) up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally \[oral-disintegrating tablet (ODT)\] up to 3 times, at different mg/kg doses, with up to 18 days between doses.
|
Part B: Prasugrel Once-Daily Dose
n=9 participants at risk
Participants who only enrolled in Part B of the study.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.
|
Part A and Part B Participants: During Part A
n=9 participants at risk
Events reported during Part A for those participants who enrolled in Part A and Part B of study.
Part A: 0.03 mg/kg up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
|
Part A and Part B Participants: During Part B
n=9 participants at risk
Events reported during Part B for those participants who enrolled in Part A and Part B of study.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Hypersplenism
|
0.00%
0/15
|
11.1%
1/9 • Number of events 2
|
0.00%
0/9
|
0.00%
0/9
|
|
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
|
13.3%
2/15 • Number of events 2
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
Other adverse events
| Measure |
Part A: Prasugrel Single Dose
n=15 participants at risk
Participants who only enrolled in Part A of the study.
Part A: 0.03 milligrams per kilogram (mg/kg) up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally \[oral-disintegrating tablet (ODT)\] up to 3 times, at different mg/kg doses, with up to 18 days between doses.
|
Part B: Prasugrel Once-Daily Dose
n=9 participants at risk
Participants who only enrolled in Part B of the study.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.
|
Part A and Part B Participants: During Part A
n=9 participants at risk
Events reported during Part A for those participants who enrolled in Part A and Part B of study.
Part A: 0.03 mg/kg up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.
|
Part A and Part B Participants: During Part B
n=9 participants at risk
Events reported during Part B for those participants who enrolled in Part A and Part B of study.
Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
22.2%
2/9 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/15
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin swelling
|
0.00%
0/15
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Muscle strain
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
|
Reproductive system and breast disorders
Penis disorder
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/15
|
0.00%
0/9
|
22.2%
2/9 • Number of events 2
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
2/15 • Number of events 2
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Congenital, familial and genetic disorders
Sickle cell anaemia
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
22.2%
2/9 • Number of events 2
|
33.3%
3/9 • Number of events 4
|
|
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
|
13.3%
2/15 • Number of events 3
|
11.1%
1/9 • Number of events 1
|
22.2%
2/9 • Number of events 2
|
11.1%
1/9 • Number of events 1
|
|
Ear and labyrinth disorders
Middle ear effusion
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Eye disorders
Eyelid bleeding
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Gastrointestinal disorders
Tooth loss
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
General disorders
Chest pain
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/15
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Hordeolum
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Infections and infestations
Otitis media
|
6.7%
1/15 • Number of events 1
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Viral infection
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.00%
0/15
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/15
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
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