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

November 17, 2011
January 17, 2014
November 2011
November 2012   (final data collection date for primary outcome measure)
  • 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.
  • Pharmacokinetics: area under the concentration-time curve (AUC) of prasugrel active metabolite (Pras-AM) [ Time Frame: Part A: 0.5 hr post-dose up to 4 hrs post single dose ] [ Designated as safety issue: No ]
  • Percentage of platelet inhibition as measured by VerifyNow™P2Y12 (VN) [ Time Frame: Part A: 4 hrs post dose after each single dose ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01476696 on ClinicalTrials.gov Archive Site
  • 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.
  • Pharmacokinetics: area under the concentration-time curve (AUC) of prasugrel inactive metabolite (Pras-AM) [ Time Frame: Part A: 0.5 hour up to 4 hrs post single dose ] [ Designated as safety issue: No ]
  • Number of Participants with Pain [ Time Frame: Part B: Baseline and First Dose Day 1 through Day 10-18 and Second Dose Day 1 through Day 10-18 ] [ Designated as safety issue: No ]
  • Number of Participants with Hemorrhagic Events Requiring Medical Intervention [ Time Frame: Part B: Baseline and First Dose Day 1 through Day 10-18 and Second Dose Day 1 through Day 10-18 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease
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).

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Sickle Cell Disease
Drug: Prasugrel
Administered orally
Other Names:
  • Effient
  • Efient
  • LY640315
  • CS-747
  • 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.
    Intervention: Drug: Prasugrel
  • 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.
    Intervention: Drug: Prasugrel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
33
November 2012
November 2012   (final data collection date for primary outcome measure)

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
Both
2 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01476696
12324, H7T-MC-TACX
No
Eli Lilly and Company
Eli Lilly and Company
Daiichi Sankyo Inc.
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
Eli Lilly and Company
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP