Sickle Cell DiseasePhase 2NCT03825341

Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere

A Phase 2 study testing Hydroxyurea and Hydroxyurea Oral Capsule in people with Sickle Cell Disease and Thalassemia, run by St. Jude Children's Research Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 9 months to 18 years
Conditions the study is for: Sickle Cell Disease, Thalassemia
What is being tested?: Hydroxyurea and Hydroxyurea Oral Capsule
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 10 Jun 2019to 20 Jan 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

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

Ages 9 months to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Show all 18Show fewer

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105

Other trials in United States

About this study

Primary Objective

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

Read the 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.

Conditions: Sickle Cell Disease, Thalassemia
Being tested: Hydroxyurea, Hydroxyurea Oral Capsule
Medical subject headings: Anemia, Sickle Cell, Thalassemia

What participants receive

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

HydroxyureaDrug
Also called HU, Liquid Hydroxyurea
Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.
Hydroxyurea Oral CapsuleDrug
Also called HU Sprinkle, Doxroxia
Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.

Study groups in NCT03825341
Study group	Role	What they receive
Arm 1 Liquid Hydroxyurea	Active comparator	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. Receives: Drug: Hydroxyurea
Arm 2 Hydroxyurea Oral Capsule	Active comparator	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 Receives: Drug: Hydroxyurea Oral Capsule

What is being measured

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

The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Summary statistics including mean, standard deviation (SD) will be reported.
Measured: 1 day
The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for HU Liquid Formulation in Infants (9 Months to <2 Years)
Summary statistics including mean, standard deviation (SD) will be reported.
Measured: 1 day
AUClast for HU Liquid Formulation in Infants (9 Months to <2 Years)
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.
Measured: 1 day
AUCinfinity for HU Liquid Formulation in Infants (9 Months to <2 Years)
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.
Measured: 1 day
Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Summary statistics including mean, standard deviation (SD) will be reported.
Measured: 1 day
Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to <2 Years)
Summary statistics including mean, standard deviation (SD) will be reported.
Measured: 1 day
Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Summary statistics including mean, standard deviation (SD) will be reported.
Measured: 1 day
Elimination Slope for HU Liquid Formulation in Infants (9 Months to <2 Years)
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.
Measured: 1 day
Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU Liquid Formulation in Infants (9 Months to <2 Years)
Summary statistics including mean, standard deviation (SD) will be reported.
Measured: 1 day

Secondary outcomes (18)

The Maximum Concentration Observed After Dosing (Cmax) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
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)
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.
Measured: 2 days
AUClast for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
AUCinfinity for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
Apparent Clearance Calculated From Dose/ AUCINF for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
Apparent Clearance Normalized for Body Weight (BW) for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
Elimination Slope for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
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.
Measured: 2 days
The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children
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.
Measured: 2 days
The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children
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.
Measured: 2 days
AUClast for Infants Versus Older Children
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.
Measured: 2 days
AUCinfinity for Infants Versus Older Children
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.
Measured: 2 days
Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children
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.
Measured: 2 days
Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children
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.
Measured: 2 days
Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children
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.
Measured: 2 days
Elimination Slope for In Infants Versus Older Children
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.
Measured: 2 days
Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children
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.
Measured: 2 days

Timeline

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

10 Jun 201920 Jan 2022

First posted31 Jan 2019
Study start10 Jun 2019
Primary completion20 Jan 2022
Study completion20 Jan 2022

Why it stopped: The study terminated early due to challenges with recruitment during the COVID pandemic.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

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

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03825341
Sponsor's protocol ID: HOPE18
Status last verified: Feb 2022
First submitted: 23 Jan 2019
Last updated: 18 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
Active, not recruitingObservational study
Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
Sickle Cell Anemia, Sickle Cell Thalassemia
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
Active, not recruitingPhase 2
A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)
Sickle Cell Disease
RecruitingPhase 3
A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD)
Sickle Cell Disease

All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere
ClinicalTrials.gov ID: NCT03825341
Acronym / sponsor ID: HOPE18
Conditions: Sickle Cell Disease, Thalassemia
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study terminated early due to challenges with recruitment during the COVID pandemic.
Enrolment: 1 participants (actual)
Lead sponsor: St. Jude Children's Research HospitalUniversity, hospital or other
Study start: 10 Jun 2019 (actual)
Primary completion: 20 Jan 2022 (actual)
Study completion: 20 Jan 2022 (actual)
First posted: 31 Jan 2019 (actual)
Results: Posted 18 Mar 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary Objective

Define the pharmacokinetics of liquid-formulated HU in infants (9 months to <2 years)
Assess the relative bioavailability of HU "sprinkles" compared to capsules in children and adolescents (≥2 to 18 years).

Secondary Objective:

Exploratory Objectives:

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm 1 Liquid Hydroxyurea	Active comparator	Drug: HydroxyureaIn 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 2 Hydroxyurea Oral Capsule	Active comparator	Drug: Hydroxyurea Oral CapsuleIn 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

Who may qualify

Ages: 9 months to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (18 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
HydroxyureaAlso: HU, Liquid HydroxyureaDrug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.	Drug	Arm 1 Liquid Hydroxyurea
Hydroxyurea Oral CapsuleAlso: HU Sprinkle, DoxroxiaDrug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.	Drug	Arm 2 Hydroxyurea Oral Capsule

Primary outcome

The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 1 day
Summary statistics including mean, standard deviation (SD) will be reported.
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
Summary statistics including mean, standard deviation (SD) will be reported.
AUClast for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 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.
AUCinfinity for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 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.
Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 1 day
Summary statistics including mean, standard deviation (SD) will be reported.
Apparent Clearance Calculated From Dose/ AUCINF for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 1 day
Summary statistics including mean, standard deviation (SD) will be reported.
Apparent Clearance Normalized for Body Weight (BW) for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 1 day
Summary statistics including mean, standard deviation (SD) will be reported.
Elimination Slope for HU Liquid Formulation in Infants (9 Months to <2 Years)
Time frame: 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.
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
Summary statistics including mean, standard deviation (SD) will be reported.

18 secondary outcomes

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
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
AUClast for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
Time frame: 2 days
AUCinfinity for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
Time frame: 2 days
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
Apparent Clearance Calculated From Dose/ AUCINF for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
Time frame: 2 days
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
Elimination Slope for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)
Time frame: 2 days
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
The Maximum Concentration Observed After Dosing (Cmax) for Infants Versus Older Children
Time frame: 2 days
The Time of Maximum Observed Concentration (Cmax) Relative to Time of Dosing for Infants Versus Older Children
Time frame: 2 days
AUClast for Infants Versus Older Children
Time frame: 2 days
AUCinfinity for Infants Versus Older Children
Time frame: 2 days
Mean Residence Time as Generated by WinNonlin (AUMC/AUC) for Infants Versus Older Children
Time frame: 2 days
Apparent Clearance Calculated From Dose/ AUCINF for In Infants Versus Older Children
Time frame: 2 days
Apparent Clearance Normalized for Body Weight (BW) for Infants Versus Older Children
Time frame: 2 days
Elimination Slope for In Infants Versus Older Children
Time frame: 2 days
Terminal Elimination Half-life Obtained From: t½ = ln(2)/ λz for Infants Versus Older Children
Time frame: 2 days

Results and safety

Results posted to the registry on 18 Mar 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1 Liquid Hydroxyurea	0	0
Arm 2 Hydroxyurea Oral Capsule	1	0

Primary outcome: The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years)

Time frame: 1 day

Population analysed: No participants were enrolled on Arm 1.

Primary outcome: 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

Population analysed: No participants were enrolled on Arm 1.

Primary outcome: AUClast for HU Liquid Formulation in Infants (9 Months to <2 Years)

Time frame: 1 day

Population analysed: No participants were enrolled on Arm 1.

Primary outcome: AUCinfinity for HU Liquid Formulation in Infants (9 Months to <2 Years)

Time frame: 1 day

Population analysed: No participants were enrolled on Arm 1.

18 secondary outcomes are reported in the full results.

Adverse events

Time frame: No participants were treated on this study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1 Liquid Hydroxyurea	0 of 0	0 of 0	0
Arm 2 Hydroxyurea Oral Capsule	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): No participants were treated on this study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
St. Jude children's Research HospitalLink provided by the sponsor.
Clinical Trials Open at St. JudeLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

Related trials for Sickle Cell Disease

RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
Active, not recruitingObservational study
Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
Sickle Cell Anemia, Sickle Cell Thalassemia
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
Active, not recruitingPhase 2
A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)
Sickle Cell Disease
RecruitingPhase 3
A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD)
Sickle Cell Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jeremie Estepp, MD principal investigator

St. Jude Children's Research Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hydroxyurea and Hydroxyurea Oral Capsule in people with Sickle Cell Disease and Thalassemia, run by St. Jude Children's Research Hospital at 1 site in United States.

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

Who may be eligible to take part?

The sponsor lists 18 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

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

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

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

What does the primary outcome measure?

The Maximum Concentration Observed After Dosing (Cmax) for HU Liquid Formulation in Infants (9 Months to <2 Years) (time frame: 1 day). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03825341.

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

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

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2022.