Pharmacokinetics (PK) of Liquid Hydroxyurea in Pediatric Patients With Sickle Cell Anemia
- Registration Number
- NCT01506544
- Lead Sponsor
- Children's Mercy Hospital Kansas City
- Brief Summary
Hydroxyurea (HU) is approved by the United States Food and Drug Administration (FDA) to treat adults with sickle cell anemia. Hydroxyurea has also been tested and used with children with sickle cell anemia. However, there are not many studies describing the disposition of drug in children less than 5 years old. The FDA has requested this study to better understand how children ages 2 to 17 years with sickle anemia absorb and eliminate the drug (this is called pharmacokinetics). The investigators will measure how much Hydroxyurea (HU) gets into the bloodstream at different time points after taking this medication.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm 2: Relative bioavailability study Hydroxyurea This will be a single dose study. Participants will receive each of the two following treatments of HU in a randomized, crossover fashion: Either approximately 20 mg/kg/day (rounded to the nearest 200mg and no greater than 30 mg/kg) or the participant's usual daily dose as: 1) a liquid containing 100 mg/mL of hydroxyurea, or 2) Droxia® 200 mg capsules administered orally. Arm 1 Pharmacokinetic study Hydroxyurea This will be a single dose study where participants will receive 20mg/kg or the participant's usual dose as a liquid containing hydroxyurea 100mg/mL. For a subset of participants (n= at least 6), a multiple-dose, steady state (i.e. at least 4 consecutive days of dosing) study will be performed.
- Primary Outcome Measures
Name Time Method Composite of Pharmacokinetics predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose Cmax, Area Under Curve, Tmax. Also, the following pharmacokinetic parameters will be derived for each participant using standard techniques: Apparent absorption rate constant, Apparent terminal elimination rate constant, Apparent steady state volume of distribution, Apparent plasma clearance. A compartment, model-based, classical fitting paradigm of the plasma concentration vs. time data will be applied to each subjects' data. Standard goodness of fit criteria will be employed. Subjects aged greater than or equal to 2 and less than or equal to 17 years.
Pharmacokinetics of HU predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose To evaluate the relative bioavailability of a liquid HU formulation (100mg/mL0 in participants ages greater that 5 and less than or equal to 17 years of age compared to standard therapy utilizing Droxia 200mg capsules
- Secondary Outcome Measures
Name Time Method Bioavailability of HU predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8 hours post-dose Relative bioavailability of liquid HU formulation in comparison to Droxia® capsules will be assessed according to published FDA Bioequivalence Guidance Subjects aged greater than 5 and less than or equal to 17 years Derived steady-state PK parameters after multiple doses of liquid HU (AUC(0-12), AUC(0-∞), Cmax, Tmax, and t½) Steady-state plasma(PK)parameters for liquid formulation of HU will be evaluated Subjects ages greater than or equal to 2 and less than or equal to 5 years will receive doses of 20mg/kg/day for at least 4 consecutive days before evaluation of the steady-state parameters
Trial Locations
- Locations (6)
Children's Memorial Hospital (Northwestern University)
🇺🇸Chicago, Illinois, United States
UT Southwestern University Hospital
🇺🇸Dallas, Texas, United States
Children's Hospital of Wisconsin
🇺🇸Wauwatosa, Wisconsin, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Columbia University Medical Center
🇺🇸New York, New York, United States