Intervention: Prasugrel
Trial phase: Phase 2
ATC code: B01AC22
SMILES: CC(=O)Oc1cc2c(s1)CCN(C(C(=O)C1CC1)c1ccccc1F)C2
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 9
Group description: 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.
Eligibility criteria:
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