Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere
Condition: Sickle Cell Disease; Thalassemia
MeSH terms: Anemia, Sickle Cell; Thalassemia
Intervention: Hydroxyurea; Hydroxyurea Oral Capsule
Intervention description: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.; Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Intervention MeSH terms: Hydroxyurea
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 9 Months
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective

        1. Define the pharmacokinetics of liquid-formulated HU in infants (9 months to <2 years)

        2. Assess the relative bioavailability of HU "sprinkles" compared to capsules in children
           and adolescents (≥2 to 18 years).

      Secondary Objective:

      Compare PK parameters in infants versus older children on this study and those from our
      previous "Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in
      Pediatric Patients with Sickle Cell Anemia" (NCT01506544) trial.

      Exploratory Objectives:

      Capture information regarding the taste of HU sprinkles using palatability questionnaire.

      This trial is an open label, single center assessment of the pharmacokinetics of two
      formulations of hydroxyurea (HU) designed to (1) determine the pharmacokinetic profile of a
      liquid formulation in infants and to (2) determine the bioavailability of "sprinkles", a
      novel method of administration for older children. The study aims to generate data to
      facilitate FDA approval for HU in children and potentially validate a new mode of
      administration ("sprinkles") that will optimize access and adherence for children in the US
      and globally.
    

Eligibility criteria:

        Inclusion Criteria:

        Participants will be eligible for this study if only if all of the following inclusion
        criteria apply:

          -  Laboratory (i.e. electrophoretic, chromatographic or DNA) confirmation of HbSS or
             HbSβ0thalassemia.

          -  Participants may or may not be currently receiving HU. If participants are taking HU,
             then their most recent dose must be ≥24 hours prior to the start of the study.

          -  Participant is in the "well" state (defined by ≥ 2 weeks since the last SCD-related
             complication).

          -  Clinical evidence of normal gastrointestinal function and structure.

          -  No clinical evidence of hepatic compromise, including transaminases < 3 times the
             upper limit of normal.

          -  Estimated glomerular filtration rate (Schwartz equation) > 70 ml/min/1.73m2.

          -  Body mass index (BMI) ≥5th and ≤95th percentile as per CDC growth charts.

        In addition:

        For the Pharmacokinetic Study (Arm 1):

          -  Age ≥ 9 months and < 2 years.

          -  Able to consume a minimum of 30 ml of water following ingestion of the study article.

        For the Bioavailability Study (Arm 2):

          -  Age ≥ 2 years and ≤ 18 years.

          -  Weight of ≥ 10 kg

          -  Females of child-bearing potential must have a negative pregnancy test prior to 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).

          -  Males of child-bearing potential must be willing to practice appropriate contraceptive
             measures, including abstinence, during study participation (30 days after last
             administration of investigational agents).

          -  Able to ingest both sprinkles and capsule study articles and consume a minimum of 30
             ml of water following ingestion of each agent.

        Exclusion Criteria:

          -  Chronic transfusion therapy, or transfused within 3 months of study participation.

          -  Known renal impairment (creatinine >1.5x the upper limit of normal for age).

          -  Known hepatic impairment or Grade 2 or higher transaminases and bilirubin levels.

          -  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 <6.0 gm/dL, absolute reticulocyte count
             <80,000/mm3, absolute neutrophil count <1000/mm3, or platelet count <80,000/mm3.

          -  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,
             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.

          -  Participants taking antiretroviral drugs (including didanosine and stavudine) due to
             increased risk of toxicity with concomitant use.

          -  Participation in another clinical intervention trial utilizing an IND/IDE agent, but
             can participate in HUGKISS since same drug agent.