<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03825341</url>
  </required_header>
  <id_info>
    <org_study_id>HOPE18</org_study_id>
    <nct_id>NCT03825341</nct_id>
  </id_info>
  <brief_title>Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere</brief_title>
  <official_title>Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Jude Children's Research Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective&#xD;
&#xD;
        1. Define the pharmacokinetics of liquid-formulated HU in infants (9 months to &lt;2 years)&#xD;
&#xD;
        2. Assess the relative bioavailability of HU &quot;sprinkles&quot; compared to capsules in children&#xD;
           and adolescents (≥2 to 18 years).&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      Compare PK parameters in infants versus older children on this study and those from our&#xD;
      previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in&#xD;
      Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial.&#xD;
&#xD;
      Exploratory Objectives:&#xD;
&#xD;
      Capture information regarding the taste of HU sprinkles using palatability questionnaire.&#xD;
&#xD;
      This trial is an open label, single center assessment of the pharmacokinetics of two&#xD;
      formulations of hydroxyurea (HU) designed to (1) determine the pharmacokinetic profile of a&#xD;
      liquid formulation in infants and to (2) determine the bioavailability of &quot;sprinkles&quot;, a&#xD;
      novel method of administration for older children. The study aims to generate data to&#xD;
      facilitate FDA approval for HU in children and potentially validate a new mode of&#xD;
      administration (&quot;sprinkles&quot;) that will optimize access and adherence for children in the US&#xD;
      and globally.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HOPE18 will be an open label, 2-arm study of HU disposition in 48 children with SCD. In Arm&#xD;
      1, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid&#xD;
      formulation of HU on a single occasion followed by PK sampling. The dose administered will be&#xD;
      ~20 mg/kg/day or the infant's usual daily dose. In Arm 2, n=30 children who range in age from&#xD;
      2 to 18 years will be administered HU, both a sprinkle formulation and capsules (Droxia® 200&#xD;
      mg), on two separate occasions separated by at least 1 day but no more than 30 days in a&#xD;
      randomized, crossover fashion. The doses of HU on each occasion will be rounded to the&#xD;
      nearest 200 mg and will not exceed 35 mg/kg or 2000 mg. We hypothesize that the PK profile of&#xD;
      the sprinkle formulation will not differ significantly from the PK profile of Droxia®&#xD;
      capsules in children and adolescents ages ≥2 - 18 years of age. Participants in both arms&#xD;
      will be followed up to 30 days from receiving last HU dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study terminated early due to challenges with recruitment during the COVID pandemic.&#xD;
  </why_stopped>
  <start_date type="Actual">June 10, 2019</start_date>
  <completion_date type="Actual">January 20, 2022</completion_date>
  <primary_completion_date type="Actual">January 20, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUClast for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCinfinity for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Slope for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</measure>
    <time_frame>1 day</time_frame>
    <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Maximum Concentration Observed After Dosing (Cmax) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinfinity for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance Calculated From Dose/ AUCINF for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance Normalized for Body Weight (BW) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination Slope for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</measure>
    <time_frame>2 days</time_frame>
    <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinfinity for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination Slope for In Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children</measure>
    <time_frame>2 days</time_frame>
    <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Sickle Cell Disease</condition>
  <condition>Thalassemia</condition>
  <arm_group>
    <arm_group_label>Arm 1 Liquid Hydroxyurea</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 Hydroxyurea Oral Capsule</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxyurea</intervention_name>
    <description>Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
    <arm_group_label>Arm 1 Liquid Hydroxyurea</arm_group_label>
    <other_name>HU</other_name>
    <other_name>Liquid Hydroxyurea</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxyurea Oral Capsule</intervention_name>
    <description>Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
    <arm_group_label>Arm 2 Hydroxyurea Oral Capsule</arm_group_label>
    <other_name>HU Sprinkle</other_name>
    <other_name>Doxroxia</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants will be eligible for this study if only if all of the following inclusion&#xD;
        criteria apply:&#xD;
&#xD;
          -  Laboratory (i.e. electrophoretic, chromatographic or DNA) confirmation of HbSS or&#xD;
             HbSβ0thalassemia.&#xD;
&#xD;
          -  Participants may or may not be currently receiving HU. If participants are taking HU,&#xD;
             then their most recent dose must be ≥24 hours prior to the start of the study.&#xD;
&#xD;
          -  Participant is in the &quot;well&quot; state (defined by ≥ 2 weeks since the last SCD-related&#xD;
             complication).&#xD;
&#xD;
          -  Clinical evidence of normal gastrointestinal function and structure.&#xD;
&#xD;
          -  No clinical evidence of hepatic compromise, including transaminases &lt; 3 times the&#xD;
             upper limit of normal.&#xD;
&#xD;
          -  Estimated glomerular filtration rate (Schwartz equation) &gt; 70 ml/min/1.73m2.&#xD;
&#xD;
          -  Body mass index (BMI) ≥5th and ≤95th percentile as per CDC growth charts.&#xD;
&#xD;
        In addition:&#xD;
&#xD;
        For the Pharmacokinetic Study (Arm 1):&#xD;
&#xD;
          -  Age ≥ 9 months and &lt; 2 years.&#xD;
&#xD;
          -  Able to consume a minimum of 30 ml of water following ingestion of the study article.&#xD;
&#xD;
        For the Bioavailability Study (Arm 2):&#xD;
&#xD;
          -  Age ≥ 2 years and ≤ 18 years.&#xD;
&#xD;
          -  Weight of ≥ 10 kg&#xD;
&#xD;
          -  Females of child-bearing potential must have a negative pregnancy test prior to dosing&#xD;
             and be willing to practice appropriate contraceptive measures, including abstinence,&#xD;
             from the time of the initial pregnancy testing through the remainder of the study (30&#xD;
             days after last administration of investigational agents).&#xD;
&#xD;
          -  Males of child-bearing potential must be willing to practice appropriate contraceptive&#xD;
             measures, including abstinence, during study participation (30 days after last&#xD;
             administration of investigational agents).&#xD;
&#xD;
          -  Able to ingest both sprinkles and capsule study articles and consume a minimum of 30&#xD;
             ml of water following ingestion of each agent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic transfusion therapy, or transfused within 3 months of study participation.&#xD;
&#xD;
          -  Known renal impairment (creatinine &gt;1.5x the upper limit of normal for age).&#xD;
&#xD;
          -  Known hepatic impairment or Grade 2 or higher transaminases and bilirubin levels.&#xD;
&#xD;
          -  Diagnoses other than sickle cell anemia or sickle beta-zero thalassemia (i.e., other&#xD;
             sickle cell variants or sickle/ hereditary persistence of fetal hemoglobin).&#xD;
&#xD;
          -  Blood count parameters as follows: hemoglobin &lt;6.0 gm/dL, absolute reticulocyte count&#xD;
             &lt;80,000/mm3, absolute neutrophil count &lt;1000/mm3, or platelet count &lt;80,000/mm3.&#xD;
&#xD;
          -  The participant has used opiates, H2 blockers, proton pump inhibitors, antacids, other&#xD;
             GI motility agents or any other medication that, in the opinion of the investigator,&#xD;
             will interfere with the study procedures or affect the interpretation of the results&#xD;
             of the study for 3 days prior to the first dose of study.&#xD;
&#xD;
          -  Participants taking antiretroviral drugs (including didanosine and stavudine) due to&#xD;
             increased risk of toxicity with concomitant use.&#xD;
&#xD;
          -  Participation in another clinical intervention trial utilizing an IND/IDE agent, but&#xD;
             can participate in HUGKISS since same drug agent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>9 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeremie Estepp, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <results_first_submitted>February 18, 2022</results_first_submitted>
  <results_first_submitted_qc>February 18, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 18, 2022</results_first_posted>
  <last_update_submitted>February 18, 2022</last_update_submitted>
  <last_update_submitted_qc>February 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxyurea</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data will be made available at the time of article publication.</ipd_time_frame>
    <ipd_access_criteria>Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT03825341/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT03825341/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>1 participant was recruited between March 2019 and Jan. 2022. The participant was randomized but did not receive treatment.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm 1 Liquid Hydroxyurea</title>
          <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
        </group>
        <group group_id="P2">
          <title>Arm 2 Hydroxyurea Oral Capsule</title>
          <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>No enrollments on Arm 1.</population>
      <group_list>
        <group group_id="B1">
          <title>Arm 1 Liquid Hydroxyurea</title>
          <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
        </group>
        <group group_id="B2">
          <title>Arm 2 Hydroxyurea Oral Capsule</title>
          <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Baseline data not entered for the 1 enrollment due to confidentiality concerns.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Baseline data not entered for the 1 enrollment due to confidentiality concerns.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>Baseline data not entered for the 1 enrollment due to confidentiality concerns.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Baseline data not entered for the 1 enrollment due to confidentiality concerns.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUClast for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUCinfinity for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCinfinity for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Elimination Slope for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Elimination Slope for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
        <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
        <time_frame>1 day</time_frame>
        <population>No participants were enrolled on Arm 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to &lt;2 Years)</title>
          <description>Summary statistics including mean, standard deviation (SD) will be reported.</description>
          <population>No participants were enrolled on Arm 1.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Maximum Concentration Observed After Dosing (Cmax) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>The Maximum Concentration Observed After Dosing (Cmax) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUCinfinity for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCinfinity for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance Calculated From Dose/ AUCINF for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Calculated From Dose/ AUCINF for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance Normalized for Body Weight (BW) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Normalized for Body Weight (BW) for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Elimination Slope for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Elimination Slope for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
        <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants treated on Arm 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU &quot;Sprinkles&quot; Compared to Capsules in Children and Adolescents (≥2 to 18 Years)</title>
          <description>Summary statistics including mean and SD will be reported for &quot;sprinkles&quot; and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants treated on Arm 2.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children</title>
        <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children</title>
          <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children</title>
        <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children</title>
          <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast for Infants Versus Older Children</title>
        <description>The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast for Infants Versus Older Children</title>
          <description>The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUCinfinity for Infants Versus Older Children</title>
        <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCinfinity for Infants Versus Older Children</title>
          <description>The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children</title>
        <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children</title>
          <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children</title>
        <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children</title>
          <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children</title>
        <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children</title>
          <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Elimination Slope for In Infants Versus Older Children</title>
        <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Elimination Slope for In Infants Versus Older Children</title>
          <description>The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children</title>
        <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
        <time_frame>2 days</time_frame>
        <population>No participants were treated on this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 Liquid Hydroxyurea</title>
            <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2 Hydroxyurea Oral Capsule</title>
            <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children</title>
          <description>The older children will include children on arm 2 on this study and those from our previous &quot;Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia&quot; (NCT01506544) trial. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.</description>
          <population>No participants were treated on this study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>No participants were treated on this study.</time_frame>
      <desc>No participants were treated on this study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm 1 Liquid Hydroxyurea</title>
          <description>In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.&#xD;
Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.</description>
        </group>
        <group group_id="E2">
          <title>Arm 2 Hydroxyurea Oral Capsule</title>
          <description>In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg&#xD;
Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>No participants were treated on this study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jeremie Estepp, MD</name_or_title>
      <organization>St. Jude Children's Research Hospital</organization>
      <phone>(901) 595-5703</phone>
      <email>jeremie.estepp@stjude.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03825341
org study id: HOPE18
nct id: NCT03825341
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
HOPE18 will be an open label, 2-arm study of HU disposition in 48 children with SCD. In Arm
      1, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid
      formulation of HU on a single occasion followed by PK sampling. The dose administered will be
      ~20 mg/kg/day or the infant's usual daily dose. In Arm 2, n=30 children who range in age from
      2 to 18 years will be administered HU, both a sprinkle formulation and capsules (Droxia® 200
      mg), on two separate occasions separated by at least 1 day but no more than 30 days in a
      randomized, crossover fashion. The doses of HU on each occasion will be rounded to the
      nearest 200 mg and will not exceed 35 mg/kg or 2000 mg. We hypothesize that the PK profile of
      the sprinkle formulation will not differ significantly from the PK profile of Droxia®
      capsules in children and adolescents ages ≥2 - 18 years of age. Participants in both arms
      will be followed up to 30 days from receiving last HU dose.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: Summary statistics including mean, standard deviation (SD) will be reported.
measure: The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: Summary statistics including mean, standard deviation (SD) will be reported.
measure: AUClast for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). Summary statistics including mean, standard deviation (SD) will be reported.
measure: AUCinfinity for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean, standard deviation (SD) will be reported.
measure: Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: Summary statistics including mean, standard deviation (SD) will be reported.
measure: Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: Summary statistics including mean, standard deviation (SD) will be reported.
measure: Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: Summary statistics including mean, standard deviation (SD) will be reported.
measure: Elimination Slope for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean, standard deviation (SD) will be reported.
measure: Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to <2 Years)
time frame: 1 day
description: Summary statistics including mean, standard deviation (SD) will be reported.
measure: The Maximum Concentration Observed After Dosing (Cmax) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: AUClast for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: AUCinfinity for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: Apparent Clearance Calculated From Dose/ AUCINF for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: Apparent Clearance Normalized for Body Weight (BW) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: Elimination Slope for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
time frame: 2 days
description: Summary statistics including mean and SD will be reported for "sprinkles" and capsules and will be compared using two-sample t-test or Wilcoxon rank sum test depending on the normality of the data at a significance level of 0.05 per study design above. Logarithmic transformation will be applied if data do not follow normal.
measure: The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children
time frame: 2 days
description: The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children
time frame: 2 days
description: The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: AUClast for Infants Versus Older Children
time frame: 2 days
description: The area under the concentration-time curve from time of dosing of the drug to the time of the last measurable concentration or when concentrations were Below the Limit of Quantitation (BLQ) were calculated using either the linear (concentration before Cmax) or log trapezoidal rule (concentrations after Cmax). The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: AUCinfinity for Infants Versus Older Children
time frame: 2 days
description: The AUC extrapolated from the last measured concentration (Clast) to time infinity using the formula AUClast + Clast / λz. The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children
time frame: 2 days
description: The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children
time frame: 2 days
description: The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children
time frame: 2 days
description: The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: Elimination Slope for In Infants Versus Older Children
time frame: 2 days
description: The first-order linear slope associated with the terminal (log-linear) portion of the curve and estimated via linear regression of log concentrations vs. time. The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
measure: Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children
time frame: 2 days
description: The older children will include children on arm 2 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. Summary statistics will be reported for the infants and older children and will be compared using two sample t-test or Wilcoxon rank sum test depending on the normality of the data. Logarithmic transformation will be applied if data do not follow normal.
arm group label: Arm 1 Liquid Hydroxyurea
arm group type: Active Comparator
description: In Arm 1 of this study, n=18 infants ages 9 months to 2 years will be administered an extemporaneous oral liquid formulation of HU on a single occasion followed by PK sampling. The dose administered will be ~20 mg/kg/day or the infant's usual daily dose.
arm group label: Arm 2 Hydroxyurea Oral Capsule
arm group type: Active Comparator
description: In Arm 2, n=30 children who range in age from 2 to 18 years will be administered oral capsule HU, both a sprinkle formulation and capsules (Droxia® 200 mg), on two separate occasions separated by at least 1 but no more than 30 days in a randomized, crossover fashion. The doses of HU on each occasion will be rounded to the nearest 200 mg and will not exceed 35 mg/kg or 2000 mg
intervention type: Drug
intervention name: Hydroxyurea
description: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
arm group label: Arm 1 Liquid Hydroxyurea
other name: HU
other name: Liquid Hydroxyurea
intervention type: Drug
intervention name: Hydroxyurea Oral Capsule
description: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
arm group label: Arm 2 Hydroxyurea Oral Capsule
other name: HU Sprinkle
other name: Doxroxia
criteria: 
gender: All
minimum age: 9 Months
maximum age: 18 Years
healthy volunteers: No
last name: Jeremie Estepp, MD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
country: United States
url: http://www.stjude.org
description: St. Jude children's Research Hospital
url: http://www.stjude.org
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Thalassemia
mesh term: Hydroxyurea
sharing ipd: Yes
ipd description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data will be made available at the time of article publication.
ipd access criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: No participants were treated on this study.
point of contact: 