Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03825341
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary Objective

1. Define the pharmacokinetics of liquid-formulated HU in infants (9 months to <2 years)

2. Assess the relative bioavailability of HU "sprinkles" compared to capsules in children and adolescents (≥2 to 18 years).

Secondary Objective:

Compare PK parameters in infants versus older children on this study and those from our previous "Pharmacokinetics and Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia" (NCT01506544) trial.

Exploratory Objectives:

Capture information regarding the taste of HU sprinkles using palatability questionnaire.

This trial is an open label, single center assessment of the pharmacokinetics of two formulations of hydroxyurea (HU) designed to (1) determine the pharmacokinetic profile of a liquid formulation in infants and to (2) determine the bioavailability of "sprinkles", a novel method of administration for older children. The study aims to generate data to facilitate FDA approval for HU in children and potentially validate a new mode of administration ("sprinkles") that will optimize access and adherence for children in the US and globally.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease; Thalassemia	Drug: Hydroxyurea; Drug: Hydroxyurea Oral Capsule	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere
• Actual Study Start Date: Jun 10, 2019
• Actual Primary Completion Date: Jan 20, 2022
• Actual Study Completion Date: Jan 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 Liquid Hydroxyurea 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.	Drug: Hydroxyurea; Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.; Other Names: HU Liquid Hydroxyurea
Active Comparator: Arm 2 Hydroxyurea Oral Capsule 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	Drug: Hydroxyurea Oral Capsule; Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.; Other Names: HU Sprinkle Doxroxia

Outcome Measures

Primary Outcome Measures

1. The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   Summary statistics including mean, standard deviation (SD) will be reported.

2. The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   Summary statistics including mean, standard deviation (SD) will be reported.

3. AUClast for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   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.

4. AUCinfinity for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   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.

5. Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   Summary statistics including mean, standard deviation (SD) will be reported.

6. Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   Summary statistics including mean, standard deviation (SD) will be reported.

7. Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   Summary statistics including mean, standard deviation (SD) will be reported.

8. Elimination Slope for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   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.

9. Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to <2 Years) [1 day]

   Summary statistics including mean, standard deviation (SD) will be reported.

Secondary Outcome Measures

1. The Maximum Concentration Observed After Dosing (Cmax) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

2. 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) [2 days]

   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.

3. AUClast for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

4. AUCinfinity for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

5. Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

6. Apparent Clearance Calculated From Dose/ AUCINF for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

7. Apparent Clearance Normalized for Body Weight (BW) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

8. Elimination Slope for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

9. Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years) [2 days]

   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.

10. The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children [2 days]

    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.

11. The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children [2 days]

    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.

12. AUClast for Infants Versus Older Children [2 days]

    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.

13. AUCinfinity for Infants Versus Older Children [2 days]

    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.

14. Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children [2 days]

    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.

15. Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children [2 days]

    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.

16. Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children [2 days]

    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.

17. Elimination Slope for In Infants Versus Older Children [2 days]

    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.

18. Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children [2 days]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Months to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Participants will be eligible for this study if only if all of the following inclusion criteria apply:

• Laboratory (i.e. electrophoretic, chromatographic or DNA) confirmation of HbSS or HbSβ0thalassemia.

• Participants may or may not be currently receiving HU. If participants are taking HU, then their most recent dose must be ≥24 hours prior to the start of the study.

• Participant is in the "well" state (defined by ≥ 2 weeks since the last SCD-related complication).

• Clinical evidence of normal gastrointestinal function and structure.

• No clinical evidence of hepatic compromise, including transaminases < 3 times the upper limit of normal.

• Estimated glomerular filtration rate (Schwartz equation) > 70 ml/min/1.73m2.

• Body mass index (BMI) ≥5th and ≤95th percentile as per CDC growth charts.

In addition:

For the Pharmacokinetic Study (Arm 1):

• Age ≥ 9 months and < 2 years.

• Able to consume a minimum of 30 ml of water following ingestion of the study article.

For the Bioavailability Study (Arm 2):

• Age ≥ 2 years and ≤ 18 years.

• Weight of ≥ 10 kg

• Females of child-bearing potential must have a negative pregnancy test prior to dosing and be willing to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy testing through the remainder of the study (30 days after last administration of investigational agents).

• Males of child-bearing potential must be willing to practice appropriate contraceptive measures, including abstinence, during study participation (30 days after last administration of investigational agents).

• Able to ingest both sprinkles and capsule study articles and consume a minimum of 30 ml of water following ingestion of each agent.

Exclusion Criteria:

• Chronic transfusion therapy, or transfused within 3 months of study participation.

• Known renal impairment (creatinine >1.5x the upper limit of normal for age).

• Known hepatic impairment or Grade 2 or higher transaminases and bilirubin levels.

• Diagnoses other than sickle cell anemia or sickle beta-zero thalassemia (i.e., other sickle cell variants or sickle/ hereditary persistence of fetal hemoglobin).

• Blood count parameters as follows: hemoglobin <6.0 gm/dL, absolute reticulocyte count <80,000/mm3, absolute neutrophil count <1000/mm3, or platelet count <80,000/mm3.

• The participant has used opiates, H2 blockers, proton pump inhibitors, antacids, other GI motility agents or any other medication that, in the opinion of the investigator, will interfere with the study procedures or affect the interpretation of the results of the study for 3 days prior to the first dose of study.

• Participants taking antiretroviral drugs (including didanosine and stavudine) due to increased risk of toxicity with concomitant use.

• Participation in another clinical intervention trial utilizing an IND/IDE agent, but can participate in HUGKISS since same drug agent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Jeremie Estepp, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 26, 2019
• Informed Consent Form - Dec 21, 2018

More Information

Additional Information:

• St. Jude children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT03825341
• Other Study ID Numbers: HOPE18
• First Posted: Jan 31, 2019
• Last Update Posted: Mar 18, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Anemia, Sickle Cell; Thalassemia; Hydroxyurea

Study Results

Participant Flow

Recruitment Details	1 participant was recruited between March 2019 and Jan. 2022. The participant was randomized but did not receive treatment.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Period Title: Overall Study
STARTED	0	1
COMPLETED	0	0
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule	Total
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.	Total of all reporting groups
Overall Participants	0	1	1
Age (Count of Participants)
<=18 years	0 NaN
Between 18 and 65 years	0 NaN
>=65 years	0 NaN
Sex: Female, Male (Count of Participants)
Female	0 NaN
Male	0 NaN
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 NaN
Not Hispanic or Latino	0 NaN
Unknown or Not Reported	0 NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN
Asian	0 NaN
Native Hawaiian or Other Pacific Islander	0 NaN
Black or African American	0 NaN
White	0 NaN
More than one race	0 NaN
Unknown or Not Reported	0 NaN

Outcome Measures

1. Primary Outcome

Title	The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Description	Summary statistics including mean, standard deviation (SD) will be reported.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

2. Primary Outcome

Title	The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to <2 Years)
Description	Summary statistics including mean, standard deviation (SD) will be reported.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

3. Primary Outcome

Title	AUClast for HU Liquid Formulation in Infants (9 Months to <2 Years)
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.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

4. Primary Outcome

Title	AUCinfinity for HU Liquid Formulation in Infants (9 Months to <2 Years)
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.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

5. Primary Outcome

Title	Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Description	Summary statistics including mean, standard deviation (SD) will be reported.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

6. Primary Outcome

Title	Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to <2 Years)
Description	Summary statistics including mean, standard deviation (SD) will be reported.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

7. Primary Outcome

Title	Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Description	Summary statistics including mean, standard deviation (SD) will be reported.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

8. Primary Outcome

Title	Elimination Slope for HU Liquid Formulation in Infants (9 Months to <2 Years)
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.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

9. Primary Outcome

Title	Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to <2 Years)
Description	Summary statistics including mean, standard deviation (SD) will be reported.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

No participants were enrolled on Arm 1.

Arm/Group Title	Arm 1 Liquid Hydroxyurea
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Measure Participants	0

10. Secondary Outcome

Title	The Maximum Concentration Observed After Dosing (Cmax) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

11. Secondary Outcome

Title	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)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

12. Secondary Outcome

Title	AUClast for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

13. Secondary Outcome

Title	AUCinfinity for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

14. Secondary Outcome

Title	Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

15. Secondary Outcome

Title	Apparent Clearance Calculated From Dose/ AUCINF for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

16. Secondary Outcome

Title	Apparent Clearance Normalized for Body Weight (BW) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

17. Secondary Outcome

Title	Elimination Slope for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

18. Secondary Outcome

Title	Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants treated on Arm 2.

Arm/Group Title	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0

19. Secondary Outcome

Title	The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

20. Secondary Outcome

Title	The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

21. Secondary Outcome

Title	AUClast for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

22. Secondary Outcome

Title	AUCinfinity for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

23. Secondary Outcome

Title	Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

24. Secondary Outcome

Title	Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

25. Secondary Outcome

Title	Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

26. Secondary Outcome

Title	Elimination Slope for In Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

27. Secondary Outcome

Title	Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children
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.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

No participants were treated on this study.

Arm/Group Title	Arm 1 Liquid Hydroxyurea	Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
Measure Participants	0	0

Adverse Events

Time Frame	No participants were treated on this study.
Adverse Event Reporting Description	No participants were treated on this study.
Arm/Group Title	Arm 1 Liquid Hydroxyurea		Arm 2 Hydroxyurea Oral Capsule
Arm/Group 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. Hydroxyurea: Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.		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 Hydroxyurea Oral Capsule: Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.
All Cause Mortality
	Arm 1 Liquid Hydroxyurea		Arm 2 Hydroxyurea Oral Capsule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Arm 1 Liquid Hydroxyurea		Arm 2 Hydroxyurea Oral Capsule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Arm 1 Liquid Hydroxyurea		Arm 2 Hydroxyurea Oral Capsule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

No participants were treated on this study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

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.