A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— Crescent  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01476696
• Other study ID #: 12324
• Secondary ID: H7T-MC-TACX
• Status: Completed
• Phase: Phase 2
• First received: November 17, 2011
• Last updated: January 17, 2014
• Start date: November 2011
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• Are male or female with SCD [(homozygous sickle cell (HbSS) and hemoglobin S beta ^0 thalassemia (HbS ß^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 ß^+ 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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Prasugrel
Administered orally

Locations

Country	Name	City	State
United States	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	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	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	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	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	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	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	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	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

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Daiichi Sankyo Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes