Status:

COMPLETED

Pharmacokinetics (PK) of Liquid Hydroxyurea in Pediatric Patients With Sickle Cell Anemia

Lead Sponsor:

Children's Mercy Hospital Kansas City

Collaborating Sponsors:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Conditions:

Sickle Cell Anemia

Eligibility:

All Genders

2-17 years

Phase:

PHASE1

Brief Summary

Hydroxyurea (HU) is approved by the United States Food and Drug Administration (FDA) to treat adults with sickle cell anemia. Hydroxyurea has also been tested and used with children with sickle cell a...

Eligibility Criteria

Inclusion

  • For Both Arms:
  • Pharmacokinetics and Relative Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell
  • The study participant will be a pediatric (male or female) participant with sickle cell anemia with laboratory (i.e. electrophoretic, chromatographic or DNA) confirmation of the diagnosis of Hemoglobin SS or Sβ0thalassemia.
  • Weight ≥ 10 kg.
  • Participants may or may not be currently receiving hydroxyurea. If participants are taking hydroxyurea, the last dose must be no less than 24 hours prior to the start of the study.
  • Participant is in the "well" state (i.e. at least 2 weeks since the last vaso-occlusive crisis, acute chest syndrome episode, or splenic sequestration episode).
  • Clinical evidence of normal gastrointestinal function and structure.
  • No clinical evidence of hepatic compromise including transaminases no more than 3 times the upper limit of normal.
  • A glomerular filtration rate (GFR--estimated from serum creatinine using age-appropriate, validated equations such as the Schwartz equation) \> 70 ml/min/1.73m2 and no known renal impairment (creatinine no more than 1.5 times the upper limit of normal for age in the screening laboratory).
  • Body mass index (BMI) ≥5th and ≤ 95th percentile as per CDC growth charts.
  • The parent or guardian is willing and able to provide a signed and dated written informed consent form prior to any study related procedures. When appropriate, the participant has signed an assent to participate according to local IRB guidelines.
  • The participants and/or participant's parents are able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions such that the participant is likely to complete the study as planned.
  • Based on the opinion of the physicians providing patient care and those conducting the study, there are no apparent contraindications for inclusion as a participant in a pharmacokinetic study.
  • For the Pharmacokinetic Study (Arm 1):
  • Participant is ≥ 2 years and ≤ 5 years of age.
  • The participant is able to consume a minimum of 30 ml of water following ingestion of the study article.
  • For the Relative Bioavailability Study:
  • Participant is \> 5 years and \< 17 years of age.
  • All females of child-bearing potential must be found to have a negative serum pregnancy test prior to initial dosing and be willing to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy testing through the remainder of the study (30 days after last administration of investigational agents).
  • The participant is able to ingest both capsule and liquid study articles and consume a minimum of 30 ml of water following ingestion of medication.
  • EXCLUSION CRITERIA
  • A participant will not be eligible for inclusion in this study if any of the following criteria apply:
  • Chronic transfusion therapy, or transfused within 3 months of study participation.
  • Known renal impairment (creatinine greater than 1.5 times the upper limit of normal for age in the screening laboratory).
  • Known hepatic impairment or elevated transaminases (greater than 3 times normal).
  • Known presence of malignancy.
  • The participant is unwilling and/or unable to abstain from use of tobacco- or nicotine-containing products for 24 hours prior to screening and for 24 hours prior to dosing until collection of the final PK sample during each treatment period.
  • Diagnoses other than sickle cell anemia or sickle beta-zero thalassemia (i.e., other sickle cell variants or sickle hereditary persistence of fetal hemoglobin).
  • Blood count parameters as follows: Hemoglobin less than 6.0 gm/dL, absolute reticulocyte count less than 80,000 mm-3, neutrophil count less than 1200 mm-3, platelet count less than 150,000 mm-3.
  • The participant has used opiates, H2 blockers, proton pump inhibitors, antacids, other GI motility agents or any other medication that, in the opinion of the investigator and/or sponsor, will interfere with the study procedures or affect the interpretation of the results of the study for 3 days prior to the first dose of study.
  • Use of over the counter non-steroidal anti-inflammatory agent or narcotic analgesic within 3 days.
  • Participant has received an investigational drug within the past 30 days.
  • Use of any illicit or illegal substances.
  • The parent or guardian is unwilling or unable to provide a signed and dated written informed consent form prior to any study related procedures, or, when appropriate, the participant has refused to sign an assent to participate according to local IRB guidelines.
  • Any other condition or chronic illness, which in the opinion of the Principal Investigator makes participation unadvised or unsafe.
  • The caregiver is unwilling or unable to provide a completed study diary for a participant in the steady-state subset.

Exclusion

    Key Trial Info

    Start Date :

    December 1 2011

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    January 1 2014

    Estimated Enrollment :

    39 Patients enrolled

    Trial Details

    Trial ID

    NCT01506544

    Start Date

    December 1 2011

    End Date

    January 1 2014

    Last Update

    December 12 2014

    Active Locations (6)

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    Page 1 of 2 (6 locations)

    1

    Children's Hospital of Alabama

    Birmingham, Alabama, United States, 35233

    2

    Children's Memorial Hospital (Northwestern University)

    Chicago, Illinois, United States, 60614-3363

    3

    Columbia University Medical Center

    New York, New York, United States, 10032

    4

    Duke University Medical Center

    Durham, North Carolina, United States, 27710