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

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01476696
First received: November 17, 2011
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Sickle Cell Disease
Drug: Prasugrel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Ranging Study of Prasugrel in Pediatric Patients With Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM) [ Time Frame: Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN) [ Time Frame: Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage) ] [ Designated as safety issue: No ]
    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:
  • Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite [ Time Frame: Part A: 0.5, 1, 1.5, 2, 4 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Pain [ Time Frame: Part B: Baseline and Day14 ± 4 days postdose in each dosing period ] [ Designated as safety issue: No ]
    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?

  • Number of Participants With Hemorrhagic Events Requiring Medical Intervention [ Time Frame: Part B: Baseline up to Day 36 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 33
Study Start Date: November 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01476696

Locations
United States, California
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
United States, District of Columbia
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
United States, Illinois
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
United States, Louisiana
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
United States, Massachusetts
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
United States, Missouri
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
United States, North Carolina
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
United States, Ohio
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
United States, Pennsylvania
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01476696     History of Changes
Other Study ID Numbers: 12324, H7T-MC-TACX
Study First Received: November 17, 2011
Results First Received: October 18, 2013
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration

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
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Prasugrel
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014