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Sickle Cell AnemiaPhase 1HUNCT01506544

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

A Phase 1 study testing Hydroxyurea in people with Sickle Cell Anemia, run by Children's Mercy Hospital Kansas City at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 17 years
Conditions the study is for
Sickle Cell Anemia
What is being tested?
Hydroxyurea
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
6 sitesUnited States
Study dates
Dec 2011to Jan 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

None listed.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Children's Memorial Hospital (Northwestern University)

    Chicago, Illinois, 60614-3363

  • UT Southwestern University Hospital

    Dallas, Texas, 75390-9063

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Wisconsin

    Wauwatosa, Wisconsin, 53226

Other trials in United States

About this study

Official title: 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.

Being tested
Hydroxyurea
Keywords
HU, Hydroxyurea, Sickle cell, Pediatric
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxyureaDrug

    Also called Droxia Capsules, Hydrea

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

Study groups in NCT01506544
Study groupRoleWhat they receive
Arm 1 Pharmacokinetic studyExperimentalThis 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.
Receives: Drug: Hydroxyurea
Arm 2: Relative bioavailability studyActive comparatorThis 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.
Receives: Drug: Hydroxyurea

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of Pharmacokinetics

    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.

    Measured: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose

  2. Pharmacokinetics of HU

    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

    Measured: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose

Secondary outcomes (1)

  1. Bioavailability of HU

    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

    Measured: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2012 (estimated)
  2. Study startDec 2011
  3. Primary completionDec 2013
  4. Study completionJan 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01506544
Sponsor's protocol ID
Hydroxyurea Pharmacokenetic
Other IDs
HHSN275201000003I
Acronym
HU
Status last verified
Dec 2014
First submitted
30 Sep 2011
Last updated
12 Dec 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28884840

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hydroxyurea in people with Sickle Cell Anemia, run by Children's Mercy Hospital Kansas City at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01506544, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2014.

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