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

Lilly

Status and phase: Completed; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: Prasugrel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01476696

12324

H7T-MC-TACX (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 33 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Part A: Prasugrel Single Dose

Experimental group

Description:

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.

Treatment:

Drug: Prasugrel

Part B: Prasugrel Once-Daily Dose

Experimental group

Description:

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.

Treatment:

Drug: Prasugrel