This study is examining the pharmacokinetics of liquid hydroxyurea in approximately 16 children aged 2 to <5 years and the relative bioavailability in approximately 24 children aged >5 to 17 years. Children enrolled must have a diagnosis of sickle cell anemia or sickle beta-zero thalassemia. The study period lasts a minimum of 30 days from the first dose.
Kathleen Neville, MD, of Children's Mercy Hospital Kansas City, discusses the PTN study of hydroxyurea in pediatric patients with sickle cell anemia.
Sickle cell anemia is a disease passed down through families in which red blood cells form an abnormal crescent shape (as opposed to the normal disc shape). Hemoglobin is a protein inside red blood cells that carries oxygen. Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S, which distorts the shape of red blood cells, especially when exposed to low oxygen levels. These fragile, sickle-shaped cells deliver less oxygen to the body's tissues. They can also clog more easily in small blood vessels and break into pieces that disrupt healthy blood flow. Almost all patients with sickle cell anemia have painful episodes that can last from hours to days. These episodes can affect the bones of the back, the long bones, and the chest, and they can be severe enough to require a hospital stay. Common symptoms of sickle cell anemia include attacks of abdominal pain, bone pain, delayed growth and puberty, fatigue, fever, and ulcers on the lower legs.
Hydroxyurea (HU) represents the only major medical breakthrough in sickle cell disease in the past 20 years, and it is the only drug that is approved by the U.S. Food and Drug Administration (FDA) for treatment in adults with sickle cell disease. Treatment with HU has been shown to significantly decrease the incidence of painful episodes and also reduces overall mortality in adult patients. In spite of the fact that the FDA has not approved HU for pediatric use, it is often used to treat children who exhibit signs of severe disease. Recent data suggest that use of HU in infants with sickle cell disease is feasible, well-tolerated, and efficacious; however, only limited pharmacokinetic (what the body does to the drug) and pharmacodynamic (effects of drugs on the body) studies of HU use in children exist.
This study was designed to better understand how this drug works in children. Approximately 40 children with sickle cell disease are being enrolled and given a liquid formulation of HU. Sixteen participants aged 2 to <5 years are being enrolled in the pharmacokinetic study, and up to 24 participants aged >5 to 17 years are being enrolled in the relative bioavailability study (in which the liquid formulation will be compared with Droxia®). Blood samples are obtained after HU administration to determine study drug concentrations in the body and its elimination. The study period is expected to last a minimum of 30 days from the first dose of HU.
Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.
Estepp JH, Melloni C, Thornburg CD, Wiczling P, Rogers Z, Rothman JA, Green NS, Liem R, Brandow AM, Crary SE, Howard TH, Morris MH, Lewandowski A, Garg U, Jusko WJ, Neville KA; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee.
Journal of Clinical Pharmacology • March 2016, volume 56, issue 3, pages 298-306. Epub: October 2015.
PubMed ID (PMID): 26201504.
Clinical study report submitted to FDA
Kathleen Neville, MD, MS
Mercy Children's Hospital
Kansas City, MO
Zora R. Rogers, MD
University of Texas Southwestern
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- PTN hydroxyurea trial opens enrollment to younger participants July 26, 2012 The PTN hydroxyurea trial has extended enrollment into Arm 1 of the study, which will target participants ages 2 to ≤5 years. Enrollment into this trial is proceeding in two stages: the first stage (Arm 2) is focusing on children 5 to 17 years of age. Fourteen of 24 participants have been enrolled into this arm ...
- PTN hydroxyurea trial prepares for interim analysis June 22, 2012 The PTN hydroxyurea trial enrolled its 7th and 8th patients on June 12 and 14, 2012, thanks to the collective efforts of Nancy Green, MD, of Columbia University Medical Center, Robert Liem, MD, of Children’s Memorial Hospital in Chicago, and Courtney Thornburg, MD, of Duke University Medical Center. Enrollment into this trial is proceeding in two ...
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- First patient enrolled in hydroxyurea study February 13, 2012 Breaking news announcement On January 27, 2012, the first patient was successfully enrolled into the PTN’s hydroxyurea (HU) study. Hydroxyurea is the only major drug breakthrough for the treatment of sickle cell disease within the past 20 years. It is the only drug approved by the FDA to treat adults with sickle cell anemia, and so it ...