Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (PTN POPS)

Determining the appropriate dosing of several understudied drugs in children using samples collected as part of regular care.

This study will characterize the pharmacokinetics of understudied drugs that are administered to children regularly by their treating physicians. Approximately 3000 children, less than 21 years of age, are participating in the study for up to 90 days (depending on how long the drug of interest is being dosed). The Pediatric Trials Network hopes to generate data to shrink the gap between pediatric and adult dosing information available to prescribing physicians for their pediatric patients. View study data for ampicillin opportunistic/PK, doxycycline opportunistic/PK, methadone opportunistic/PK, ondansetron opportunistic/PK, or trimethoprim- sulfamethoxazole (Bactrim) opportunistic/PK on NICHD's Data and Specimen Hub (DASH).

Micky Cohen-Wolkowiez, MD, PhD, of the Duke Clinical Research Institute, discusses the PTN POPS study.

Summary

Many drugs prescribed in Asia, Europe and North America lack specific dosing recommendations for children. These gaps in information about pediatric drug dosing, safety, and efficacy place children at risk for adverse events and therapeutic failure.

Earlier studies relying on standard-of-care procedures have successfully characterized the pharmacokinetics (i.e., what the body does to the drug) of drugs used in children. These studies did not actually administer drugs to children but rather collected samples from children who were already receiving the drugs as part of standard medical care.

Similarly, in this study, understudied drugs are being administered to children by their treating physicians according to local standards of care. The only study procedure involves biological sample collection during the time of drug administration. Approximately 3000 children aged <21 years who are receiving these drugs are being enrolled and will be followed for up to 90 days.

The goal of this study is to characterize the pharmacokinetics of understudied drugs for which specific dosing recommendations and safety data are lacking. The prescribing of drugs to children will not be part of this study. By taking advantage of procedures done as part of routine medical care (for example, blood draws), this study will provide better understanding of drug exposure in children. The data collected will also provide valuable pharmacokinetic and dosing information for drugs in different pediatric age groups, as well as special pediatric populations (such as obese children).

Publications

  • Systemic Timolol Exposure Following Topical Application to Infantile Hemangiomas Journal of the American Academy of Dermatology • February 2019. Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee. Off-label ophthalmic timolol has been rapidly adopted for treatment of infantile hemangioma since topical application of beta-blockers was presumed to have an improved safety profile compared to oral ...
  • A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data Journal of Pharmacokinetics and Pharmacodynamics • June 2018. Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M. Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about ...
  • Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children The Journal of Clinical Pharmacology • April 2018. Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, Ng KC, Delmore P, Harper BL, Melloni C, Lewandowski A, Gelber C, Cohen-Wolkowiez M, Lee JH; Pediatric Trial Network Steering Committee. Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in ...
  • Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates Therapeutic Drug Monitoring • February 2018. Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Blackford M, Yogev R, James LP, Melloni C, Harper B, Mitchell J, Benjamin DK Jr, Boakye-Agyeman F, Cohen-Wolkowiez M. Dried blood spot (DBS) is a practical sampling strategy for pharmacokinetic studies in neonates. The utility of DBS to determine the population ...
  • Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children Antimicrobial Agents and Chemotherapy • December 2017. Autmizguine J, Melloni C, Hornik CP, Dallefeld S, Harper B, Yogev R, Sullivan JE, Atz AM, Al-Uzri A, Mendley S, Poindexter B, Mitchell J, Lewandowski A, Delmore P, Cohen-Wolkowiez M, Gonzalez D; the Pediatric Trials Network Steering Committee. Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including ...
  • Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone The Journal of Pediatrics • April 2017. Virkud YV, Hornik CP, Benjamin DK, Laughon MM, Clark RH, Greenberg RG, Smith PB. To assess how neonatal intensive care units followed the American Academy of Pediatrics guidelines for use of dexamethasone in preterm infants by evaluating respiratory support at the time of dexamethasone administration. This is an observational study ...
  • Pharmacokinetics of Clindamycin in Obese and Nonobese Children Antimicrobial Agents and Chemotherapy • March 2017. Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee. Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for ...
  • Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates Journal of Pediatrics • August 2016. Hornik CP, Benjamin DK Jr, Smith PB, Pencina MJ, Tremoulet AH, Capparelli EV, Ericson JE, Clark RH, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act—Pediatric Trials Network. This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR ...
  • Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants Antimicrobial Agents and Chemotherapy • April 2016. Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM. Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population ...
  • Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants Journal of Pediatric Gastroenterology and Nutrition • August 2015. Ericson JE, Arnold C, Cheeseman J, Cho J, Kaneko S, Wilson E, Clark RH, Benjamin DK Jr, Chu V, Smith PB, Hornik CP; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee. Prokinetic medications are used in premature infants to promote motility and decrease time to full ...
  • Rifampin use and safety in hospitalized infants American Journal of Perinatology • May 2015. Arnold CJ, Ericson J, Kohman J, Corey KL, Oh M, Onabanjo J, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB, Chu VH; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee. This study aims to examine the use and safety of rifampin in hospitalized infants. Observational study of ...
  • Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots Bioanalysis • May 2015. Gonzalez D, Melloni C, Poindexter BB, Yogev R, Atz AM, Sullivan JE, Mendley SR, Delmore P, Delinsky A, Zimmerman K, Lewandowski A, Harper B, Lewis KC, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee. Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and ...
  • Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents Clinical Pharmacology and Therapeutics • September 2014. Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, Sullivan JE, Autmizguine J, Lewandowski A, Harper B, Watt KM, Lewis KC, Capparelli EV, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee. Clindamycin is commonly prescribed to treat children with ...
  • Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design Antimicrobial Agents and Chemotherapy • June 2014. Tremoulet A, Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Salgado A, Ian-U Chong S, Melloni C, Gao J, Benjamin DK Jr, Capparelli EV, Cohen-Wolkowiez M; Administrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network. Although ampicillin is the most commonly used drug in neonates, ...

 

OVERVIEW

Status:
Enrolling

ClinicalTrials.gov identifier:
NCT01431326

NICHD Data and Specimen Hub (DASH):

Principal Investigator:
Chiara Melloni, MD, MHS
Duke Health, Durham, NC

NEWS

  • PTN welcomes first sites in Australia The Pediatric Trials Network (PTN) welcomed its first two Australian sites in February. Sydney Children’s Hospitals Network and the Royal Children’s Hospital in Melbourne are now participating in PTN’s Pharmacokinetics of Understudied Drugs in Infants and Children (POPS) study. The sites are currently involved in the Paediatric Trials Network Australia (PTNA), a counterpart of PTN that ...
  • 15 IDeA sites welcomed into PTN POPS study Fifteen sites in states participating in the NIH Institutional Development Award (IDeA) program are being onboarded into the Pediatric Trials Network’s (PTN) POPS study of commonly used medications in children. The IDeA program aims to build research capacities in states that have historically received low levels of NIH funding by supporting research, faculty development, and infrastructure ...
  • PTN determines appropriate TMP/SMX dosing in infants and children The Pediatric Trials Network (PTN), with funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), recently completed a multicenter study of trimethoprim/sulfamethoxazole (TMP/SMX) to determine appropriate dosing for infants and children. The results of the study were published in the journal Antimicrobial Agents and Chemotherapy on Oct. 30. TMP/SMX is ...
  • POPS Paradigm Explained PTN studies managed via the POPS paradigm seek to determine the appropriate dosing of understudied drugs in children by using samples collected as part of regular care (for example, blood draws). The data collected provides valuable pharmacokinetic and dosing information for drugs in different pediatric age groups and special pediatric populations (such as obese children). Dr. ...
  • A POPS site goes above and beyond For an example of an outstanding PTN site, look no further than Ann & Robert H. Lurie Children’s Hospital of Chicago. The top enrolling site for the POPS study, Lurie Children’s has enrolled 244 patients as of September 22. To put this number into perspective, the second highest enrolling POPS site has recruited 117 patients, ...
  • The POPS study grows by leaps and bounds The POPS study is moving full steam ahead. In September 2012, the study received additional funding from the National Institute of Child Health and Human Development to effectively double in size, increasing the number of patients enrolled from 500 to ~1000 and doubling the number of participating sites from ~15 to ~30. And the new year ...