A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease

NCT01476696 | Completed Phase 2 Results

• 2 other identifiers: 12324H7T-MC-TACX
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Sickle Cell Disease

Keywords

Sickle cell disease; pediatrics; SCD; children; child; kids; pain crisis; sickle cell anemia; sickle cell pain

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite

  Part A: 0.5, 1, 1.5, 2, 4 hours postdose

• Number of Participants With Pain

  Part B: Baseline and Day14 ± 4 days postdose in each dosing period

• Number of Participants With Hemorrhagic Events Requiring Medical Intervention

  Part B: Baseline up to Day 36

Study Arms (2)

Part A: Prasugrel Single Dose

EXPERIMENTAL

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

Part B: Prasugrel Once-Daily Dose

EXPERIMENTAL

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

Interventions

Prasugrel DRUG

Administered orally

Also known as: Effient, Efient, LY640315, CS-747

Part A: Prasugrel Single Dose; Part B: Prasugrel Once-Daily Dose

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Daiichi Sankyo: collaborator

Study Sites (9)

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, 94609, United States

Location

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 D.C., District of Columbia, 20060, United States

Location

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, 60614, United States

Location

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, 70112, United States

Location

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, 02115, United States

Location

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, 63104, United States

Location

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, 27599, United States

Location

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, 45229, United States

Location

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, 15224, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Data for the Primary Outcome Measures 1 and 2 were collected for presentation of results in a scatter plot and were not intended to be summarized due to the limited number of participants per treatment.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 22, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 13, 2014
• Results First Posted: December 11, 2013

Record last verified: 2014-01

Locations

US (9)