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

An Open-Label, Dose-Ranging Study of Prasugrel in Pediatric Patients With Sickle Cell Disease

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

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Prasugrel

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94609
      • 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.
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • 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.
  • Illinois
    • Chicago, Illinois, United States, 60614
      • 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.
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • 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.
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • 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.
  • Missouri
    • St Louis, Missouri, United States, 63104
      • 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.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • 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.
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • 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.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; LY640315; CS-747; Efient
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; LY640315; CS-747; Efient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)	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.	Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)	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.	Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite	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.	Part A: 0.5, 1, 1.5, 2, 4 hours postdose
Number of Participants With Pain	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?	Part B: Baseline and Day14 ± 4 days postdose in each dosing period
Number of Participants With Hemorrhagic Events Requiring Medical Intervention	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.	Part B: Baseline up to Day 36

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: 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 record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: November 17, 2011
• First Submitted That Met QC Criteria: November 17, 2011
• First Posted (Estimate): November 22, 2011

Study Record Updates

• Last Update Posted (Estimate): February 13, 2014
• Last Update Submitted That Met QC Criteria: January 17, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: pediatrics; children; child; SCD; Sickle cell disease; sickle cell anemia; pain crisis; sickle cell pain; kids
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride
• Other Study ID Numbers: 12324; H7T-MC-TACX (Other Identifier: Eli Lilly and Company)