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

December 10, 2014 updated by: Kathleen A Neville, Children's Mercy Hospital Kansas City

Pharmacokinetics and Relative Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients With Sickle Cell Anemia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Illinois
      • Chicago, Illinois, United States, 60614-3363
        • Children's Memorial Hospital (Northwestern University)
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • UT Southwestern University Hospital
    • Wisconsin
      • Wauwatosa, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: NON_RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 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.
Drug: Hydroxyurea
20mg/kg of Hydroxyurea or the patient's standard daily dose
Other Names:
  • Hydrea
  • Droxia Capsules
ACTIVE_COMPARATOR: 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.
Drug: Hydroxyurea
20mg/kg of Hydroxyurea or the patient's standard daily dose
Other Names:
  • Hydrea
  • Droxia Capsules

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite of Pharmacokinetics
Time Frame: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose
Cmax, Area Under Curve, Tmax. Also, the following pharmacokinetic parameters will be derived for each participant using standard techniques: Apparent absorption rate constant, Apparent terminal elimination rate constant, Apparent steady state volume of distribution, Apparent plasma clearance. A compartment, model-based, classical fitting paradigm of the plasma concentration vs. time data will be applied to each subjects' data. Standard goodness of fit criteria will be employed. Subjects aged greater than or equal to 2 and less than or equal to 17 years.
predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose
Pharmacokinetics of HU
Time Frame: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose
To evaluate the relative bioavailability of a liquid HU formulation (100mg/mL0 in participants ages greater that 5 and less than or equal to 17 years of age compared to standard therapy utilizing Droxia 200mg capsules
predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bioavailability of HU
Time Frame: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8 hours post-dose
Relative bioavailability of liquid HU formulation in comparison to Droxia® capsules will be assessed according to published FDA Bioequivalence Guidance Subjects aged greater than 5 and less than or equal to 17 years Derived steady-state PK parameters after multiple doses of liquid HU (AUC(0-12), AUC(0-∞), Cmax, Tmax, and t½) Steady-state plasma(PK)parameters for liquid formulation of HU will be evaluated Subjects ages greater than or equal to 2 and less than or equal to 5 years will receive doses of 20mg/kg/day for at least 4 consecutive days before evaluation of the steady-state parameters
predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Mercy Hospital Kansas City

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kathleen Neville, MD, MS, Children's Mercy Hosptials and Clinics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2013

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 30, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 10, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 12, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Hydroxyurea Pharmacokenetic
  • HHSN275201000003I (Other Identifier: National Institute of Child Health & Human Development)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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