Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

NCT01431326 — Completed, 3520 participants, Daniel Benjamin
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RegistryNCT01431326, acronym PTN_POPS
StatusCompleted
Study typeObservational
Enrollment3520 (Actual)
SponsorDaniel Benjamin (Other); collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
ConditionsAdenovirus, Anesthesia, Anxiety, Anxiolysis, Autism, Autistic Disorder, Bacterial Meningitis, Bacterial Septicemia, Benzodiazepine, Bipolar Disorder, Bone and Joint Infections, Central Nervous System Infections, Convulsions, Cytomegalovirus Retinitis, Early-onset Schizophrenia Spectrum Disorders, Epilepsy, General Anesthesia, Gynecologic Infections, Herpes Simplex Virus, Infantile Hemangioma, Infection, Inflammation, Inflammatory Conditions, Intra-abdominal Infections, Lower Respiratory Tract Infections, Migraines, Pain, Pneumonia, Schizophrenia, Sedation, Seizures, Skeletal Muscle Spasms, Skin and Skin-structure Infections, Treatment-resistant Schizophrenia, Urinary Tract Infections, Withdrawal, Sepsis, Gram-negative Infection, Bradycardia, Cardiac Arrest, Cardiac Arrhythmia, Staphylococcal Infections, Nosocomial Pneumonia, Neuromuscular Blockade, Methicillin Resistant Staphylococcus Aureus, Endocarditis, Neutropenia, Headache, Fibrinolytic Bleeding, Pulmonary Arterial Hypertension, CMV Retinitis, Hypertension, Chronic Kidney Diseases, Hyperaldosteronism, Hypokalemia, Heart Failure, Hemophilia, Heavy Menstrual Bleeding, Insomnia
InterventionsThe POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care: (Drug)
Datesstart 2011-11-01, primary completion 2019-11-01, completion 2019-11-01, first posted 2011-09-09, last updated 2023-09-06
Locations52 sites in United States, Canada, Israel, Singapore, United Kingdom

Related Papers Related Patents Related Grants Related Experts
All trials for Adenovirus All trials for Anesthesia All trials of The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:

-Summary

Understudied drugs will be administered to children per standard of care as prescribed by their treating caregiver and only biological sample collection during the time of drug administration will be involved. A total of approximately 7000 children aged <21 years who are receiving these drugs for standard of care will be enrolled and will be followed for up a maximum of 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 protocol. Taking advantage of procedures done as part of routine medical care (i.e. blood draws) this study will serve as a tool to better understand drug exposure in children receiving these drugs per standard of care. The data collected through this initiative will also provide valuable pharmacokinetic and dosing information of drugs in different pediatric age groups as well as special pediatric populations (i.e. obese).

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+Detailed description

The purpose of this study is to characterize the PK ( Pharmacokinetics) of understudied drugs administered to children per standard of care as prescribed by their treating caregiver. This will be accomplished by the collection of biological samples during the time of drug administration per standard of care as prescribed by the caregiver. The prescribing of drugs to children will not be part of this protocol.

Aim #1: Evaluate the PK of understudied drugs currently being administered to children.

Hypothesis #1: The PK of understudied drugs in children will differ from adults and within children according to pediatric age groups or special population.

Aim #2: Explore the pharmacodynamics (PD) of understudied drugs currently being administered to children.

Hypothesis #2: The PD of targeted drugs in children will differ from adults.

Aim #3: Evaluate the influence of genetic factors, metabolic and protein profiles on therapeutic exposure.

Hypothesis #3: Genetic polymorphisms in drug metabolizing enzymes and metabolic and proteomic profiles will impact drug exposure in children.

+Arms and interventions

  • The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care: (Drug), also known as cidofovir, ciprofloxacin, methylprednisolone, tobramycin, alfentanil, clozapine, haloperidol, lurasidone, molindone, pentobarbital, warfarin (oral), ziprasidone, amikacin, cefepime, nafcillin, piperacillin-tazobactam, rocuronium, vecuronium, vancomycin, aminocaproic acid, bosentan, fosfomycin, labetalol, nifedipine, oxycodone, sevelamer carbonate, spironolactone, tranexamic acid, zolpidem

+Outcome measures

Primary outcomes

  • Composite of pharmacokinetic outcomes for understudied drugs in children [Data will be collected throughout the hospital or outpatient stay up to 90 days]: As appropriate for each study drug, the following additional PK parameters will be estimated: * maximum concentration (Cmax) * time to achieve maximum concentration (Tmax) * absorption rate constant (ka) * elimination rate constant (kel) * half-life (t1/2) * area under the curve (AUC) Penetration into body fluids will be determined by comparing exposure (i.e. AUC, Cmax) ratios between the body fluid and plasma or comparison of concentrations in paired samples.

Secondary outcomes

  • Composite pharmacodynamic outcomes of understudied drugs in children [Data will be collected throughout the hospital or outpatient stay up to 90 days]: When applicable, Monte Carlo simulations will be performed to evaluate therapeutic target attainment rates (pharmacodynamics) in the population of interest. The final PK model and parameters estimated in the population PK analysis will be used to perform these simulations.
  • Biomarkers associated with understudied drugs in children [Data will be collected throughout the hospital or outpatient stay up to 90 days]: The dosing, sampling, and demographic information recorded on the electronic data collection forms will be merged with the bioanalytical information to create a biomarker dataset for each study drug. Biomarkers will be identified using metabolomics/proteomics and pharmacogenomics methodologies. Samples for biomarker analysis will be stored for future use in a PTN designated biorepository. Associations between biomarkers and drug exposure will be explored by visual inspection (i.e. scatter plots) and statistical comparisons as needed.

+Eligibility

Sex: All, ages: any to 21 Years

Inclusion Criteria:

* 1\) Children (< 21 years of age) who are receiving understudied drugs of interest per standard of care as prescribed by their treating caregiver

Exclusion Criteria:

* 1\) Failure to obtain consent/assent (as indicated)
* 2\) Known pregnancy as determined via interview or testing if available.

+Locations (52)

FacilityCityCountryStatus
Alaska Native Medical CenterAnchorage, AlaskaUnited States
Arkansas Children's HospitalLittle Rock, ArkansasUnited States
University of California at San Diego Medical CenterLa Jolla, CaliforniaUnited States
Axis Clinical TrialsLos Angeles, CaliforniaUnited States
University of California, Los Angeles Medical CenterLos Angeles, CaliforniaUnited States
The Children's Hospital ColoradoAurora, ColoradoUnited States
Yale New Haven Children's HospitalNew Haven, ConnecticutUnited States
Alfred I. DuPont Hospital for ChildrenWilmington, DelawareUnited States
Children's National Medical CenterWashington D.C., District of ColumbiaUnited States
University of Florida Jacksonville Shands Medical CenterJacksonville, FloridaUnited States
Kapiolani Womens and Childrens Medical CenterHonolulu, HawaiiUnited States
Lurie Children's Hospital of ChicagoChicago, IllinoisUnited States
Riley Hospital for Children at Indiana UniversityIndianapolis, IndianaUnited States
University of Kansas Medical CenterFairway, KansasUnited States
Children's Mercy Hospital and ClinicsKansas City, KansasUnited States
Wesley Medical CenterWichita, KansasUnited States
Norton Children's HospitalLouisville, KentuckyUnited States
Tulane University Health Science CenterNew Orleans, LouisianaUnited States
Ochsner Baptist Clinical Trials UnitNew Orleans, LouisianaUnited States
University of MarylandBaltimore, MarylandUnited States
Children's Hospital of MichiganDetroit, MichiganUnited States
University of Mississippi Medical CenterJackson, MississippiUnited States
Children's Mercy Hospitals and ClinicsKansas City, MissouriUnited States
University of MontanaMissoula, MontanaUnited States
University of Nebraska Medical CenterOmaha, NebraskaUnited States
Dartmouth-Hitchcock Medical CenterLebanon, New HampshireUnited States
University of New Mexico, Health Sciences CenterAlbuquerque, New MexicoUnited States
UNC Hospital Neonatal-Perinatal MedicineChapel Hill, North CarolinaUnited States
Duke University Medical Center (PICU / NICU)Durham, North CarolinaUnited States
Cincinnati Childrens Hospital Medical CenterCincinnati, OhioUnited States
Rainbow Babies and Children's HospitalCleveland, OhioUnited States
Akron Children's HospitalCleveland, OhioUnited States
Board of Regents of the University of OklahomaOklahoma City, OklahomaUnited States
Oregon Health and Science UniversityPortland, OregonUnited States
Rhode Island HospitalProvidence, Rhode IslandUnited States
Medical University of South CarolinaCharleston, South CarolinaUnited States
University of South CarolinaColumbia, South CarolinaUnited States
University of Utah Hospitals and ClinicsSalt Lake City, UtahUnited States
University of Vermont Medical CenterBurlington, VermontUnited States
University of Virginia Children's HospitalCharlottesville, VirginiaUnited States
Seattle Children's HospitalSeattle, WashingtonUnited States
West Virginia University HospitalMorgantown, West VirginiaUnited States
Medical College of WisconsinMilwaukee, WisconsinUnited States
Manitoba Institute of Child HealthWinnipeg, ManitobaCanada
Children's Hospital of Eastern OntarioOttawa, OntarioCanada
The Hospital for Sick ChildrenToronto, OntarioCanada
Hospital Sainte-JustineMontreal, QuebecCanada
Assaf Harofeh Medical CenterZerifin, Tel AvivIsrael
Schneider Children's Medical Center of IsraelPetah TikvaIsrael
KK Women's and Children's Hospital Pte LtdSingaporeSingapore
Southampton General HospitalSouthampton, HampshireUnited Kingdom
Alder Hey Children's HospitalLiverpool, MerseysideUnited Kingdom

+Publications

  • Results publication: 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. Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother. 2014 Jun;58(6):3013-20. doi: 10.1128/AAC.02374-13. Epub 2014 Mar 10. PMID 24614374
  • Results publication: 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. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014 Oct;96(4):429-37. doi: 10.1038/clpt.2014.134. Epub 2014 Jun 20. PMID 24949994
  • Results publication: 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. Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots. Bioanalysis. 2015;7(9):1137-49. doi: 10.4155/bio.15.38. PMID 26039810
  • Results publication: 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. Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates. J Pediatr. 2016 Nov;178:125-129.e1. doi: 10.1016/j.jpeds.2016.07.011. Epub 2016 Aug 10. PMID 27522443
  • Results publication: 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 Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2888-94. doi: 10.1128/AAC.03086-15. Print 2016 May. PMID 26926644
  • Results publication: 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. Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01813-17. doi: 10.1128/AAC.01813-17. Print 2018 Jan. PMID 29084742
  • Results publication: 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. Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates. Ther Drug Monit. 2018 Feb;40(1):103-108. doi: 10.1097/FTD.0000000000000466. PMID 29271816
  • Results publication: 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. A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):419-430. doi: 10.1007/s10928-018-9576-y. Epub 2018 Feb 12. PMID 29435949
  • Results publication: 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. Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol. 2018 Aug;58(8):1092-1104. doi: 10.1002/jcph.1116. Epub 2018 Apr 20. PMID 29677389
  • Results publication: Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee (See Acknowledgments for a listing of committee members.). Systemic timolol exposure following topical application to infantile hemangiomas. J Am Acad Dermatol. 2020 Mar;82(3):733-736. doi: 10.1016/j.jaad.2019.02.029. Epub 2019 Feb 18. No abstract available. PMID 30790601
  • Results publication: Hornik CP, Yogev R, Mourani PM, Watt KM, Sullivan JE, Atz AM, Speicher D, Al-Uzri A, Adu-Darko M, Payne EH, Gelber CE, Lin S, Harper B, Melloni C, Cohen-Wolkowiez M, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents. J Clin Pharmacol. 2019 Dec;59(12):1606-1619. doi: 10.1002/jcph.1499. Epub 2019 Jul 17. PMID 31317556
  • Results publication: Maharaj AR, Gonzalez D, Cohen-Wolkowiez M, Hornik CP, Edginton AN. Improving Pediatric Protein Binding Estimates: An Evaluation of alpha1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet. 2018 May;57(5):577-589. doi: 10.1007/s40262-017-0576-7. PMID 28779462
  • Results publication: Maharaj AR, Wu H, Zimmerman KO, Speicher DG, Sullivan JE, Watt K, Al-Uzri A, Payne EH, Erinjeri J, Lin S, Harper B, Melloni C, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis. J Clin Pharmacol. 2020 May;60(5):636-647. doi: 10.1002/jcph.1562. Epub 2019 Dec 8. PMID 31814149
  • Results publication: Thompson EJ, Wu H, Melloni C, Balevic S, Sullivan JE, Laughon M, Clark KM, Kalra R, Mendley S, Payne EH, Erinjeri J, Gelber CE, Harper B, Cohen-Wolkowiez M, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Doxycycline in Children. Antimicrob Agents Chemother. 2019 Sep 9;63(12):e01508-19. doi: 10.1128/AAC.01508-19. Epub 2019 Sep 23. PMID 31548185
  • Results publication: Ge S, Mendley SR, Gerhart JG, Melloni C, Hornik CP, Sullivan JE, Atz A, Delmore P, Tremoulet A, Harper B, Payne E, Lin S, Erinjeri J, Cohen-Wolkowiez M, Gonzalez D; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents. Clin Transl Sci. 2020 Nov;13(6):1189-1198. doi: 10.1111/cts.12803. Epub 2020 May 27. PMID 32324313
  • Results publication: Maharaj AR, Wu H, Zimmerman KO, Autmizguine J, Kalra R, Al-Uzri A, Sherwin CMT, Goldstein SL, Watt K, Erinjeri J, Payne EH, Cohen-Wolkowiez M, Hornik CP. Population pharmacokinetics of olanzapine in children. Br J Clin Pharmacol. 2021 Feb;87(2):542-554. doi: 10.1111/bcp.14414. Epub 2020 Jul 5. PMID 32497307
  • Results publication: Commander SJ, Wu H, Boakye-Agyeman F, Melloni C, Hornik CD, Zimmerman K, Al-Uzri A, Mendley SR, Harper B, Cohen-Wolkowiez M, Hornik CP; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation. J Clin Pharmacol. 2021 Mar;61(3):368-377. doi: 10.1002/jcph.1739. Epub 2020 Oct 7. PMID 33029806
  • Results publication: Wu YSS, Cohen-Wolkowiez M, Hornik CP, Gerhart JG, Autmizguine J, Cobbaert M, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole. Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0214920. doi: 10.1128/AAC.02149-20. Epub 2021 Jun 17. PMID 33903114
  • Results publication: Maharaj AR, Wu H, Zimmerman KO, Muller WJ, Sullivan JE, Sherwin CMT, Autmizguine J, Rathore MH, Hornik CD, Al-Uzri A, Payne EH, Benjamin DK Jr, Hornik CP; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity. Paediatr Drugs. 2021 Sep;23(5):499-513. doi: 10.1007/s40272-021-00460-4. Epub 2021 Jul 23. PMID 34302290
  • Results publication: Gerhart JG, Carreno FO, Ford JL, Edginton AN, Perrin EM, Watt KM, Muller WJ, Atz AM, Al-Uzri A, Delmore P, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity. CPT Pharmacometrics Syst Pharmacol. 2022 Jun;11(6):778-791. doi: 10.1002/psp4.12793. Epub 2022 May 2. PMID 35491971
  • Results publication: Karatza E, Ganguly S, Hornik CD, Muller WJ, Al-Uzri A, James L, Balevic SJ, Gonzalez D. External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data. Front Pharmacol. 2022 Mar 17;13:817276. doi: 10.3389/fphar.2022.817276. eCollection 2022. PMID 35370711
  • Results publication: 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. Pharmacokinetics of Clindamycin in Obese and Nonobese Children. Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02014-16. doi: 10.1128/AAC.02014-16. Print 2017 Apr. PMID 28137820
  • Results publication: Sinha J, Zimmerman K, Balevic SJ, Hornik C, Muller WJ, Rathore M, Meyer M, Finkelstein Y, Al-Uzri A, Lakhotia A, Goldstein S, Chen JY, Anand R, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Population Pharmacokinetic Modeling of Oxcarbazepine and Its Active Metabolite 10-Monohydroxy Derivative to Inform Dosing in Children with Obesity. Clin Pharmacokinet. 2026 Feb;65(2):329-344. doi: 10.1007/s40262-025-01579-0. Epub 2025 Nov 17. PMID 41247430
  • Results publication: Hornik CP, Wu H, Edginton AN, Watt K, Cohen-Wolkowiez M, Gonzalez D. Development of a Pediatric Physiologically-Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data. Clin Pharmacokinet. 2017 Nov;56(11):1343-1353. doi: 10.1007/s40262-017-0525-5. PMID 28290120

+Investigators