Hydroxyurea Therapy: Optimizing Access in Pediatric Populations Everywhere

NCT03825341 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HOPE18
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective

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

Conditions

Sickle Cell Disease; Thalassemia

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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)

  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)

  2 days

• AUClast for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)

  2 days

• AUCinfinity for HU "Sprinkles" Compared to Capsules in Children and Adolescents (≥2 to 18 Years)

  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)

  2 days

Study Arms (2)

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.

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

Drug: Hydroxyurea Oral Capsule

Interventions

Hydroxyurea DRUG

Drug: Hydroxyurea oral liquid dose administered will be 20mg/kg/day or infants's usual daily dose.

Also known as: HU, Liquid Hydroxyurea

Arm 1 Liquid Hydroxyurea

Hydroxyurea Oral Capsule DRUG

Drug: Hydroxyurea both a sprinkle formulation and capsules (Droxia 200mg) administered on 2 separate occasions.

Also known as: HU Sprinkle, Doxroxia

Arm 2 Hydroxyurea Oral Capsule

Eligibility Criteria

• Age: 9 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

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

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Limitations and Caveats

No participants were treated on this study.

Results Point of Contact

• Title: Jeremie Estepp, MD
• Organization: St. Jude Children's Research Hospital

jeremie.estepp@stjude.org

(901) 595-5703

Study Officials

• Jeremie Estepp, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: January 31, 2019
• Study Start: June 10, 2019
• Primary Completion: January 20, 2022
• Study Completion: January 20, 2022
• Last Updated: March 18, 2022
• Results First Posted: March 18, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)