PTN hydroxyurea trial enrolls its last patient

On October 23, 2013, the site team at St. Jude Children’s Research Hospital in Memphis, TN, enrolled the last patient into the PTN hydroxyurea study. Overall, 8 sites—Duke University Medical Center, Medical College of Wisconsin, Columbia University Medical Center, Ann & Robert H. Lurie Children’s Hospital of Chicago, Children’s of Alabama, University of Arkansas for Medical Sciences, University of Texas Southwestern, and St. Jude—worked very hard to enroll the 39 patients needed for this study.

Hydroxyurea represents the only major medical breakthrough in sickle cell disease in the past 20 years, and it is the only drug approved by the U.S. Food and Drug Administration (FDA) for use in adults with sickle cell. In spite of the fact that it is not labeled for use in children, hydroxyurea is often used to treat children who exhibit signs of severe sickle cell disease. Recent data suggest that its use in infants with sickle cell is feasible, well-tolerated, and efficacious; however, only limited pharmacokinetic and pharmacodynamic studies of hydroxyurea use in children exist.

This study was designed to better understand how this drug works in children and to confirm its safety profile. Participants were given capsules or a liquid formulation of hydroxyurea, and blood samples were obtained after administration to determine drug concentrations in the body and its elimination. Study results are expected by the first half of 2014.

Acyclovir PK study is complete

The PTN open-label study to describe the pharmacokinetics (PK) of acyclovir in premature infants has concluded, with results recently published in the Pediatric Infectious Diseases Journal.

Acyclovir is a drug used to treat herpes simplex virus (HSV) infections in infants. HSV is a very serious infection in those <6 months of age, often resulting in death or profound mental retardation. Appropriate dosing of acyclovir is known for adults and children but has not been adequately studied in full-term or premature neonates.

This study examined acyclovir levels in the blood of premature and term infants who were placed on the drug to treat a suspected HSV infection, thereby determining the appropriate dose in this vulnerable population. Investigators found that infant maturity as measured by post-menstrual age* is associated with the infant body’s ability to clear the drug; in short, they determined that less frequent dosing is needed in younger infants to achieve optimal therapeutic benefit.

The study was conducted at two sites — Duke University Medical Center in Durham, North Carolina, and Wesley Medical Center in Wichita, Kansas. Site teams headed by Robert Lenfestey (Duke) and Paula Delmore (Wesley) enrolled 32 patients over the 9-month study. Next steps will involve a retrospective analysis of data from infants who received high-dose acyclovir; this information will support proposed label changes submitted to the Food and Drug Administration for use of acyclovir in infants.

* Post-menstrual age is the time elapsed between the first day of the mother’s last menstrual period and the infant’s birth, plus the time elapsed since birth.

The PTN lisinopril study completes enrollment

In spite of the challenges posed by its complex protocol, the “Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients” study has completed enrollment, with a total of 26 patients contributing data to this study of lisinopril use for the control of high blood pressure in kids receiving kidney transplants.

This accomplishment is due to the exceptional efforts of the study teams at 8 sites: University of Alabama–Birmingham, Arkansas Children’s Hospital in Little Rock, University of Michigan at Ann Arbor, New York University Langone Medical Center, Albert Einstein University Hospital in New York, Cincinnati Children’s Hospital, Children’s Mercy Hospital in Kansas City, and Emory University & Children’s Healthcare of Atlanta.

Lisinopril is a drug used in children ages 6 and up to treat high blood pressure, a condition commonly seen among children and adolescents who receive kidney transplants. Unfortunately, the appropriate dose of lisinopril in these especially vulnerable patients is not currently known. This PTN study is evaluating the safety of lisinopril in pediatric participants who have a stable functioning kidney transplant and high blood pressure. It is also examining what young bodies do to the drug (a.k.a. the drug’s pharmacokinetics).

Preliminary results are expected later this year.

The Institute of Medicine releases report on pediatric studies conducted under BPCA and PREA

The Institute of Medicine (IOM) released a report today that finds that federal laws motivating or requiring drugmakers to conduct pediatric studies have yielded important information to guide the use of medications in children.

Titled “Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act,” the report also notes that studies involving children continue to be limited and suggests avenues to improvement, such as strengthening the design and execution of pediatric studies requested under BPCA or required by PREA, as well as expanding the research scope to include more long-term safety studies and studies in neonates.

The report’s release precedes the 2012 Congressional vote on reauthorization of both BPCA and PREA, which occurs every five years. As directed by Congress, the Food and Drug Administration (FDA) asked the IOM to convene a committee to review aspects of pediatric studies and changes in product labeling that resulted from these legislative acts. Of note, since the two policies were adopted, the FDA has approved 400 labeling changes for drugs used in children.

More information about the IOM report may be found at:

PTN study of clindamycin dosing in obese children enrolls first patients

The University of Louisville in Kentucky and Children’s Mercy Hospital of Kansas City, Missouri, have enrolled the first two patients into the PTN study of the safety and pharmacokinetics of clindamycin in obese children. Principal investigators Michael Smith, MD, (Louisville) and Jen Goldman, MD, (Children’s Mercy) both enrolled their participants on August 8, marking the start of this trial to determine optimal dosing of the drug in young people with a body mass index ≥85th percentile for age.

Clindamycin is considered a first-line therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), an infection that often occurs in obese patients. Because excess weight results in altered body composition, physiology, and resulting changes in drug distribution, dosing guidelines based on normal weight adults cannot be extrapolated to their overweight and obese counterparts, and especially not to obese children.

Rates of childhood obesity have risen over the past decade, thus making it critical that safety and efficacy studies of drugs used in kids and adolescents be conducted to ensure effective treatment. The PTN clindamycin study will help to fill this knowledge gap; initial results are anticipated in mid 2014.