Crescent: A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01476696
• Collaborator: Daiichi Sankyo, Inc. (Industry)
• Enrollment: 33
• Locations: 9
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the correct prasugrel dosage to be given to children with sickle cell disease (SCD).

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Prasugrel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Dose-Ranging Study of Prasugrel in Pediatric Patients With Sickle Cell Disease
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Prasugrel Single Dose Prasugrel 0.03 milligrams per kilogram (mg/kg) to 0.60 mg/kg dosage to be titrated up or down based on desired platelet inhibition, administered orally [oral-disintegrating tablet (ODT)], single dose given up to 3 occasions, at different strengths, with up to 18 days between doses.	Drug: Prasugrel; Administered orally; Other Names: Effient Efient LY640315 CS-747
Experimental: Part B: Prasugrel Once-Daily Dose Daily prasugrel dose (mg/kg) that is expected to achieve mean platelet activation inhibition of 30% administered orally, once daily for 10-18 days and then followed by prasugrel dose (mg/kg) that is expected to achieve mean platelet activation inhibition of 50% administered orally, once daily for 10-18 days, for a total of 20-36 days.	Drug: Prasugrel; Administered orally; Other Names: Effient Efient LY640315 CS-747

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM) [Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose]

   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.

2. Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN) [Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage)]

   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.

Secondary Outcome Measures

1. Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite [Part A: 0.5, 1, 1.5, 2, 4 hours postdose]

   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.

2. Number of Participants With Pain [Part B: Baseline and Day14 ± 4 days postdose in each dosing period]

   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?

3. Number of Participants With Hemorrhagic Events Requiring Medical Intervention [Part B: Baseline up to Day 36]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are male or female with SCD [(homozygous sickle cell (HbSS) and hemoglobin S beta ^{0 thalassemia (HbS β}0 thalassemia)]

• Have a body weight ≥12 kilograms (kg) and are ≥2 to <18 years of age at the time of screening

• If participants are ≥2 and ≤16 years of age, have had a transcranial Doppler within the last year

• Participants on hydroxyurea must be on a stable dose for the 60 days prior to enrollment without signs of hematologic toxicity at screening

• Have a legal representative that is in competent mental condition to provide written informed consent on behalf of the study participant before entering the study. The child may be required to give documented assent, if required by local regulations.

• If sexually active, has a negative pregnancy test at screening (if female) and agrees to use a reliable method of birth control during the study (for both males and females)

Exclusion Criteria:

• Known to have hemoglobin C sickle cell (HbSC) or hemoglobin S beta ^{plus thalassemia (HbS β}+ thalassemia) genotypes

• Vaso-occlusive crisis (VOC) requiring medical attention within 15 days prior to screening

• Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator is associated with reduced survival

• Hepatic dysfunction characterized by alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN)

• Renal dysfunction requiring chronic dialysis or creatinine ≥ 1.5 milligrams per deciliter (mg/dL)

• Contraindication for antiplatelet therapy

• History of intolerance or allergy to approved thienopyridines (clopidogrel, ticlopidine, or prasugrel)

• Participants with a hematocrit <18%

• History of abnormal or conditional transcranial Doppler [velocity in middle cerebral or carotid artery ≥170 centimeters per second (cm/sec)] within the last year

• Any history of bleeding diathesis

• Any history of renal papillary necrosis

• Active internal bleeding

• History of spontaneous gastrointestinal bleeding

• Gross hematuria or > 300 red blood cells (RBC)/high-powered field (HPF) on urinalysis at the time of screening

• Any history of vitreous hemorrhage

• Prior history of hemorrhagic or ischemic stroke, a transient ischemic attack (TIA), or other intracranial hemorrhage

• Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding

• Platelet count <100,000 per microliter (μl) of blood

• Have had recent surgery (within 30 days prior to screening) or are scheduled to undergo surgery within the next 60 days

• History of dysfunctional uteral bleeding, in the judgment of the investigator

• Treatment with packed RBC or whole blood transfusion therapy within 30 days prior to dosing

• Any nonsteroidal anti-inflammatory drug (NSAID) use within 5 days prior to screening

• Any aspirin, warfarin, thienopyridine, or other antiplatelet medication use within 10 days prior to dosing

• Anticipated use of aspirin, warfarin, thienopyridine, or other antiplatelet medication during the study period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oakland	California	United States	94609
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Washington	District of Columbia	United States	20060
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chicago	Illinois	United States	60614
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New Orleans	Louisiana	United States	70112
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boston	Massachusetts	United States	02115
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	St Louis	Missouri	United States	63104
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chapel Hill	North Carolina	United States	27599
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45229
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pittsburgh	Pennsylvania	United States	15224

Sponsors and Collaborators

• Eli Lilly and Company
• Daiichi Sankyo, Inc.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC-GMT-5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01476696
• Other Study ID Numbers: 12324; H7T-MC-TACX
• First Posted: Nov 22, 2011
• Last Update Posted: Feb 13, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Eli Lilly and Company: Sickle cell disease; pediatrics; SCD; children; child; kids; pain crisis; sickle cell anemia; sickle cell pain
• Additional relevant MeSH terms: Anemia, Sickle Cell; Prasugrel Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Part A: Prasugrel Single Dose	Part B: Prasugrel Once-Daily Dose	Part A Then Part B: Prasugrel Single Dose Then Once-Daily Dose
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	15	9	9
Received at Least 1 Dose of Study Drug	15	9	9
COMPLETED	12	8	9
NOT COMPLETED	3	1	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	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.
Overall Participants	33
Age, Customized (participants) [Number]
≥2 and ≤5 years	7 21.2%
≥6 and ≤11 years	14 42.4%
≥12 and ≤17 years	12 36.4%
Sex: Female, Male (Count of Participants)
Female	19 57.6%
Male	14 42.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3%
Not Hispanic or Latino	32 97%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (participants) [Number]
Native Hawaiian or Other Pacific Islander	1 3%
Black or African American	32 97%
Region of Enrollment (participants) [Number]
United States	33 100%
Height (centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters (cm)]	139.21 (22.663)
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	38.55 (18.785)
Body Mass Index (kilograms per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per square meter (kg/m^2)]	18.64 (4.091)
Genotype (participants) [Number]
HbSS	30 90.9%
HbS Beta^0 Thalassemia	3 9.1%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
Description	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.
Time Frame	Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of prasugrel.

Arm/Group Title	Entire Study Population
Arm/Group Description	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.
Measure Participants	33
Part A: 0.03 mg/kg (n=2)	8.68 (36)
Part A: 0.05 mg/kg (n=2)	14.5 (44)
Part A: 0.07 mg/kg (n=2)	20.8 (31)
Part A: 0.09 mg/kg (n=2)	31.3 (25)
Part A: 0.11 mg/kg (n=1)	22.2 (NA)
Part A: 0.13 mg/kg (n=2)	50.3 (20)
Part A: 0.15 mg/kg (n=2)	35.2 (86)
Part A: 0.2 mg/kg (n=2)	43.7 (48)
Part A: 0.25 mg/kg (n=3)	60.7 (88)
Part A: 0.3 mg/kg (n=6)	87.9 (52)
Part A: 0.35 mg/kg (n=11)	111 (59)
Part A: 0.4 mg/kg (n=14)	108 (55)
Part A: 0.45 mg/kg (n=8)	136 (53)
Part A: 0.5 mg/kg (n=7)	186 (36)
Part A: 0.55 mg/kg (n=1)	87.0 (NA)
Part A: 0.6 mg/kg (n=3)	299 (4)
Part B: 0.06 mg/kg (n=7)	16.3 (50)
Part B: 0.08 mg/kg (n=17)	27.1 (20)
Part B: 0.12 mg/kg (n=8)	38.5 (15)

2. Primary Outcome

Title	Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
Description	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.
Time Frame	Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of prasugrel.

Arm/Group Title	Entire Study Population
Arm/Group Description	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.
Measure Participants	33
Part A: 0.03 mg/kg (n=2)	2.0 (2.83)
Part A: 0.05 mg/kg (n=2)	0.0 (0.00)
Part A: 0.07 mg/kg (n=2)	0.0 (0.00)
Part A: 0.08 mg/kg (n=18)	7.7 (9.35)
Part A: 0.09 mg/kg (n=2)	2.5 (3.54)
Part A: 0.11 mg/kg (n=1)	0.0 (NA)
Part A: 0.13 mg/kg (n=2)	9.5 (13.44)
Part A: 0.15 mg/kg (n=2)	4.0 (0.00)
Part A: 0.2 mg/kg (n=2)	0.0 (0.00)
Part A: 0.25 mg/kg (n=3)	18.0 (18.52)
Part A: 0.3 mg/kg (n=6)	42.3 (27.21)
Part A: 0.35 mg/kg (n=11)	38.0 (28.46)
Part A: 0.4 mg/kg (n=14)	39.1 (26.77)
Part A: 0.45 mg/kg (n=8)	35.3 (27.16)
Part A: 0.5 mg/kg (n=7)	55.9 (27.85)
Part A: 0.55 mg/kg (n=1)	31.0 (NA)
Part A: 0.6 mg/kg (n=3)	70.3 (19.22)
Part B: 0.06 mg/kg (n=8)	38.6 (21.07)
Part B: 0.08 mg/kg (n=18)	37.8 (25.86)
Part B: 0.12 mg/kg (n=8)	48.1 (11.29)

3. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite
Description	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.
Time Frame	Part A: 0.5, 1, 1.5, 2, 4 hours postdose

Outcome Measure Data

Analysis Population Description

No participants were analyzed.

Arm/Group Title	Part A: Prasugrel Single Dose
Arm/Group Description	Part A of the study: 0.03 up to 0.60 milligrams per kilogram (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.
Measure Participants	0

4. Secondary Outcome

Title	Number of Participants With Pain
Description	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?
Time Frame	Part B: Baseline and Day14 ± 4 days postdose in each dosing period

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Baseline	Part B: Prasugrel Once-Daily Dose (0.06 mg/kg)	Part B: Prasugrel Once-Daily Dose (0.08 mg/kg)	Part B: Prasugrel Once-Daily Dose (0.12 mg/kg)
Arm/Group Description	Participants in Part B of the study, prior to receiving treatment (Prasugrel once-daily doses).	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.	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.	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.
Measure Participants	18	9	17	8
Number [participants]	6 18.2%	4 NaN	1 NaN	2 NaN

5. Secondary Outcome

Title	Number of Participants With Hemorrhagic Events Requiring Medical Intervention
Description	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.
Time Frame	Part B: Baseline up to Day 36

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of prasugrel.

Arm/Group Title	Part B: Prasugrel Once-Daily Dose
Arm/Group Description	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.
Measure Participants	18
Number [participants]	0 0%

Adverse Events

Arm/Group Title	Part A: Prasugrel Single Dose		Part B: Prasugrel Once-Daily Dose		Part A and Part B Participants: During Part A		Part A and Part B Participants: During Part B
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Part A: Prasugrel Single Dose		Part B: Prasugrel Once-Daily Dose		Part A and Part B Participants: During Part A		Part A and Part B Participants: During Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Prasugrel Single Dose		Part B: Prasugrel Once-Daily Dose		Part A and Part B Participants: During Part A		Part A and Part B Participants: During Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		2/9 (22.2%)		0/9 (0%)		0/9 (0%)
Blood and lymphatic system disorders
Hypersplenism	0/15 (0%)	0	1/9 (11.1%)	2	0/9 (0%)	0	0/9 (0%)	0
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis	2/15 (13.3%)	2	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome	1/15 (6.7%)	1	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Part A: Prasugrel Single Dose		Part B: Prasugrel Once-Daily Dose		Part A and Part B Participants: During Part A		Part A and Part B Participants: During Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)		4/9 (44.4%)		6/9 (66.7%)		6/9 (66.7%)
Congenital, familial and genetic disorders
Sickle cell anaemia	1/15 (6.7%)	1	0/9 (0%)	0	2/9 (22.2%)	2	3/9 (33.3%)	4
Sickle cell anaemia with crisis	2/15 (13.3%)	3	1/9 (11.1%)	1	2/9 (22.2%)	2	1/9 (11.1%)	1
Ear and labyrinth disorders
Middle ear effusion	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Eye disorders
Eyelid bleeding	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Gastrointestinal disorders
Constipation	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Tooth loss	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
General disorders
Chest pain	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Pyrexia	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	1/9 (11.1%)	1
Vessel puncture site pain	0/15 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Infections and infestations
Hordeolum	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Otitis media	1/15 (6.7%)	1	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Viral infection	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Injury, poisoning and procedural complications
Animal bite	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Contusion	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Excoriation	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	1/9 (11.1%)	1
Fall	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Muscle strain	1/15 (6.7%)	1	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Wound haemorrhage	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Back pain	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Pain in extremity	1/15 (6.7%)	1	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	0/6 (0%)	0	1/4 (25%)	1	0/4 (0%)	0	0/4 (0%)	0
Penis disorder	0/6 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/15 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2	0/9 (0%)	0
Cough	2/15 (13.3%)	2	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Epistaxis	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Nasal congestion	0/15 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	1/9 (11.1%)	1
Oropharyngeal pain	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Rhinorrhoea	1/15 (6.7%)	1	0/9 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2
Wheezing	1/15 (6.7%)	1	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/15 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Rash papular	0/15 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Skin swelling	0/15 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0

Limitations/Caveats

Data for the Primary Outcome Measures 1 and 2 were collected for presentation of results in a scatter plot and were not intended to be summarized due to the limited number of participants per treatment.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.