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

NCT ID: NCT01506544

Last Updated: 2014-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2014-01-31

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 anemia. However, there are not many studies describing the disposition of drug in children less than 5 years old. The FDA has requested this study to better understand how children ages 2 to 17 years with sickle anemia absorb and eliminate the drug (this is called pharmacokinetics). The investigators will measure how much Hydroxyurea (HU) gets into the bloodstream at different time points after taking this medication.

Conditions

Sickle Cell Anemia

Keywords

HU; Hydroxyurea; Sickle cell; Pediatric

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Arm 1 Pharmacokinetic study

This will be a single dose study where participants will receive 20mg/kg or the participant's usual dose as a liquid containing hydroxyurea 100mg/mL. For a subset of participants (n= at least 6), a multiple-dose, steady state (i.e. at least 4 consecutive days of dosing) study will be performed.

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

20mg/kg of Hydroxyurea or the patient's standard daily dose

Arm 2: Relative bioavailability study

This will be a single dose study. Participants will receive each of the two following treatments of HU in a randomized, crossover fashion: Either approximately 20 mg/kg/day (rounded to the nearest 200mg and no greater than 30 mg/kg) or the participant's usual daily dose as: 1) a liquid containing 100 mg/mL of hydroxyurea, or 2) Droxia® 200 mg capsules administered orally.

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

20mg/kg of Hydroxyurea or the patient's standard daily dose

Interventions

Hydroxyurea

20mg/kg of Hydroxyurea or the patient's standard daily dose

Intervention Type: DRUG

Other Intervention Names

Droxia Capsules; Hydrea

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Kathleen A Neville

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kathleen Neville, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hosptials and Clinics

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Children's Memorial Hospital (Northwestern University)

Chicago, Illinois, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

UT Southwestern University Hospital

Dallas, Texas, United States

Children's Hospital of Wisconsin

Wauwatosa, Wisconsin, United States

Countries

United States

References

Estepp JH, Wiczling P, Moen J, Kang G, Mack JM, Liem R, Panepinto JA, Garg U, Kearns G, Neville KA. Hydroxycarbamide in children with sickle cell anaemia after first-dose vs. chronic therapy: pharmacokinetics and predictive models for drug exposure. Br J Clin Pharmacol. 2018 Jul;84(7):1478-1485. doi: 10.1111/bcp.13426. Epub 2017 Nov 28.

Reference Type: DERIVED

PMID: 28884840 (View on PubMed)

Other Identifiers

HHSN275201000003I

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Hydroxyurea Pharmacokenetic

Identifier Type: -

Identifier Source: org_study_id