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Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care (PTN_POPS)

This study is currently recruiting participants.
Verified March 2017 by Daniel Benjamin, Duke University Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT01431326
First Posted: September 9, 2011
Last Update Posted: March 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
OpAns, LLC
Information provided by (Responsible Party):
Daniel Benjamin, Duke University Medical Center
  Purpose
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 3000 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).

Condition Intervention
Adenovirus Adrenal Insufficiency Airway Swelling Anesthesia Anxiety Anxiolysis Autism Autistic Disorder Bacterial Meningitis Bacterial Septicemia Benzodiazepine Bipolar Disorder Bone and Joint Infections Brain Swelling Central Nervous System Infections Convulsions Cytomegalovirus Retinitis Early-onset Schizophrenia Spectrum Disorders Edema Epilepsy General Anesthesia Gynecologic Infections Headaches Herpes Simplex Virus Hypertension Infantile Hemangioma Infection Inflammation Inflammatory Conditions Influenza Intra-abdominal Infections Lower Respiratory Tract Infections Migraines Pain Pneumonia Prophylaxis Schizophrenia Sedation Seizures Skeletal Muscle Spasms Skin and Skin-structure Infections Stable Angina Thromboprophylaxis Thrombosis Treatment-resistant Schizophrenia Urinary Tract Infection Withdrawal Drug: The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

Resource links provided by NLM:


Further study details as provided by Daniel Benjamin, Duke University Medical Center:

Primary Outcome Measures:
  • Composite of pharmacokinetic outcomes for understudied drugs in children [ Time Frame: 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 Outcome Measures:
  • Composite pharmacodynamic outcomes of understudied drugs in children [ Time Frame: 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 [ Time Frame: Data will be collected throughout the hospital or outpatient stay up to 90 days ]
    The dosing, sampling, and demographic information recorded on the eCRF 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.


Biospecimen Retention:   Samples With DNA
whole blood

Estimated Enrollment: 10000
Study Start Date: November 2011
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:
    Other Names:
    • aripiprazole
    • ceftazidime
    • cidofovir
    • ciprofloxacin
    • dexamethasone
    • diazepam
    • levetiracetam
    • meropenem
    • methylprednisolone
    • midazolam
    • nicardipine
    • olanzapine
    • oseltamivir
    • oxycarbazepine
    • phosphenytoin
    • quetiapine
    • risperidone
    • timolol
    • topiramate
    • valproic acid
    • tobramycin
    • alfentanil
    • clozapine
    • fosphenytoin
    • haloperidol
    • heparin (low molecular weight)
    • hydromorphone
    • lurasidone
    • molindone
    • morphine
    • pentobarbital
    • propofol
    • warfarin (oral)
    • ziprasidone
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children (<21 years of age) receiving drugs per standard of care as prescribed by treating caregiver
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01431326


Contacts
Contact: Chiara Melloni, MD 919-668-8646 chiara.melloni@dm.duke.edu
Contact: Barrie L Harper, MT (ASCP) 919-668-8291 barrie.harper@duke.edu

  Show 37 Study Locations
Sponsors and Collaborators
Daniel Benjamin
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
OpAns, LLC
Investigators
Principal Investigator: Michael Cohen-Wolkowiez, MD Duke University
Study Chair: Chiara Melloni, MD Duke University
  More Information

Additional Information:
Publications:
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Shah SS, Hall M, Goodman DM, Feuer P, Sharma V, Fargason C Jr, Hyman D, Jenkins K, White ML, Levy FH, Levin JE, Bertoch D, Slonim AD. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007 Mar;161(3):282-90. Erratum in: Arch Pediatr Adolesc Med. 2007 Jul;161(7):655.
de Hoog M, Schoemaker RC, Mouton JW, van den Anker JN. Vancomycin population pharmacokinetics in neonates. Clin Pharmacol Ther. 2000 Apr;67(4):360-7.
García B, Barcia E, Pérez F, Molina IT. Population pharmacokinetics of gentamicin in premature newborns. J Antimicrob Chemother. 2006 Aug;58(2):372-9. Epub 2006 Jun 16.
Wade KC, Wu D, Kaufman DA, Ward RM, Benjamin DK Jr, Sullivan JE, Ramey N, Jayaraman B, Hoppu K, Adamson PC, Gastonguay MR, Barrett JS; National Institute of Child Health and Development Pediatric Pharmacology Research Unit Network. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother. 2008 Nov;52(11):4043-9. doi: 10.1128/AAC.00569-08. Epub 2008 Sep 22.
Capparelli E, Hochwald C, Rasmussen M, Parham A, Bradley J, Moya F. Population pharmacokinetics of cefepime in the neonate. Antimicrob Agents Chemother. 2005 Jul;49(7):2760-6.
Spooner N, Lad R, Barfield M. Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method. Anal Chem. 2009 Feb 15;81(4):1557-63. doi: 10.1021/ac8022839.
Cheung CY, van der Heijden J, Hoogtanders K, Christiaans M, Liu YL, Chan YH, Choi KS, van de Plas A, Shek CC, Chau KF, Li CS, van Hooff J, Stolk L. Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation. Transpl Int. 2008 Feb;21(2):140-5. Epub 2007 Oct 17.
Allanson AL, Cotton MM, Tettey JN, Boyter AC. Determination of rifampicin in human plasma and blood spots by high performance liquid chromatography with UV detection: a potential method for therapeutic drug monitoring. J Pharm Biomed Anal. 2007 Aug 15;44(4):963-9. Epub 2007 Apr 19.
Hibberd SG, Alveyn C, Coombes EJ, Holgate ST. Acute and chronic pharmacokinetics of asymmetrical doses of slow release choline theophyllinate in asthma. Br J Clin Pharmacol. 1986 Sep;22(3):337-41.
Meyer DM, Jessen ME. Results of extracorporeal membrane oxygenation in children with sepsis. The Extracorporeal Life Support Organization. Ann Thorac Surg. 1997 Mar;63(3):756-61.
Green TP, Timmons OD, Fackler JC, Moler FW, Thompson AE, Sweeney MF. The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Crit Care Med. 1996 Feb;24(2):323-9.
Cohen P, Collart L, Prober CG, Fischer AF, Blaschke TF. Gentamicin pharmacokinetics in neonates undergoing extracorporal membrane oxygenation. Pediatr Infect Dis J. 1990 Aug;9(8):562-6.
Amaker RD, DiPiro JT, Bhatia J. Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 1996 May;40(5):1139-42.
Dagan O, Klein J, Bohn D, Koren G. Effects of extracorporeal membrane oxygenation on morphine pharmacokinetics in infants. Crit Care Med. 1994 Jul;22(7):1099-101.
Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006 Apr 5;295(13):1549-55.
Srinivasan V, Nadkarni VM, Helfaer MA, Carey SM, Berg RA; American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators. Childhood obesity and survival after in-hospital pediatric cardiopulmonary resuscitation. Pediatrics. 2010 Mar;125(3):e481-8. doi: 10.1542/peds.2009-1324. Epub 2010 Feb 22.
Winnike JH, Li Z, Wright FA, Macdonald JM, O'Connell TM, Watkins PB. Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans. Clin Pharmacol Ther. 2010 Jul;88(1):45-51. doi: 10.1038/clpt.2009.240. Epub 2010 Feb 24.
Zheng H, Webber S, Zeevi A, Schuetz E, Zhang J, Lamba J, Bowman P, Burckart GJ. The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients. Hum Immunol. 2002 Sep;63(9):765-70.
Wilson JT. An update on the therapeutic orphan. Pediatrics. 1999 Sep;104(3 Pt 2):585-90.
Ceci A, Felisi M, Baiardi P, Bonifazi F, Catapano M, Giaquinto C, Nicolosi A, Sturkenboom M, Neubert A, Wong I. Medicines for children licensed by the European Medicines Agency (EMEA): the balance after 10 years. Eur J Clin Pharmacol. 2006 Nov;62(11):947-52. Epub 2006 Oct 5.
Benjamin DK Jr, Smith PB, Murphy MD, Roberts R, Mathis L, Avant D, Califf RM, Li JS. Peer-reviewed publication of clinical trials completed for pediatric exclusivity. JAMA. 2006 Sep 13;296(10):1266-73.
't Jong GW, Vulto AG, de Hoog M, Schimmel KJ, Tibboel D, van den Anker JN. Unapproved and off-label use of drugs in a children's hospital. N Engl J Med. 2000 Oct 12;343(15):1125.
Pullen J, Stolk LM, Nieman FH, Degraeuwe PL, van Tiel FH, Zimmermann LJ. Population pharmacokinetics and dosing of amoxicillin in (pre)term neonates. Ther Drug Monit. 2006 Apr;28(2):226-31.
Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. Review.
Fischer S, Bohn D, Rycus P, Pierre AF, de Perrot M, Waddell TK, Keshavjee S. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry. J Heart Lung Transplant. 2007 May;26(5):472-7.
Lequier L. Extracorporeal life support in pediatric and neonatal critical care: a review. J Intensive Care Med. 2004 Sep-Oct;19(5):243-58. Review.
Frenckner B, Radell P. Respiratory failure and extracorporeal membrane oxygenation. Semin Pediatr Surg. 2008 Feb;17(1):34-41. Review.
Rajagopal SK, Almond CS, Laussen PC, Rycus PT, Wypij D, Thiagarajan RR. Extracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: a review of the Extracorporeal Life Support Organization registry. Crit Care Med. 2010 Feb;38(2):382-7. doi: 10.1097/CCM.0b013e3181bc8293.
Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet. 2003;42(5):403-17. Review.
Southgate WM, DiPiro JT, Robertson AF. Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 1989 Jun;33(6):817-9.
Dodge WF, Jelliffe RW, Zwischenberger JB, Bellanger RA, Hokanson JA, Snodgrass WR. Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. Ther Drug Monit. 1994 Dec;16(6):552-9.
Bhatt-Mehta V, Johnson CE, Schumacher RE. Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy. 1992;12(1):28-32.
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Buck ML. Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy. 1998 Sep-Oct;18(5):1082-6.
Bhatt-Meht V, Annich G. Sedative clearance during extracorporeal membrane oxygenation. Perfusion. 2005 Oct;20(6):309-15.
Mehta NM, Halwick DR, Dodson BL, Thompson JE, Arnold JH. Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment. Intensive Care Med. 2007 Jun;33(6):1018-24. Epub 2007 Apr 3.
Mulla H, Lawson G, von Anrep C, Burke MD, Upton DU, Firmin RK, Killer H. In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion. 2000 Jan;15(1):21-6.
Poggesi I, Benedetti MS, Whomsley R, Le Lamer S, Molimard M, Watelet JB. Pharmacokinetics in special populations. Drug Metab Rev. 2009;41(3):422-54. doi: 10.1080/10837450902891527. Review.
Buhimschi IA, Buhimschi CS. The role of proteomics in the diagnosis of chorioamnionitis and early-onset neonatal sepsis. Clin Perinatol. 2010 Jun;37(2):355-74. doi: 10.1016/j.clp.2010.03.002. Review.
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Responsible Party: Daniel Benjamin, Professor of Pediatrics, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01431326     History of Changes
Other Study ID Numbers: Pro00029638
IND 113645 ( Other Identifier: FDA )
IND 114369 ( Other Identifier: FDA )
IND 114531 ( Other Identifier: FDA )
IND 114892 ( Other Identifier: FDA )
IND 115226 ( Other Identifier: FDA )
IND 118329 ( Other Identifier: FDA )
IND 118358 ( Other Identifier: FDA )
HHSN20100006 ( Other Grant/Funding Number: NICHD )
HHSN27500020 ( Other Grant/Funding Number: NICHD )
HHSN27500027 ( Other Grant/Funding Number: NICHD )
HHSN27500043 ( Other Grant/Funding Number: NICHD )
First Submitted: August 17, 2011
First Posted: September 9, 2011
Last Update Posted: March 22, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Completed study datasets (limited PHI) may be requested from https://pediatrictrials.org/data-sharing-opportunities

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel Benjamin, Duke University Medical Center:
adenovirus
adrenal insufficiency
afterload inducer
amnestic
anaesthetic
anesthesia
angina
anticoagulant
anti-epileptic
anti-inflammatory
antimicrobial
anti-psychotic
antiviral
anxiety
anxiolysis
anxiolytic
autism
autistic disorder
benzodiazepine
bipolar disorder
convulsions
edema
epilepsy
headaches
herpes simplex virus
HSV
hypertension
infantile hemangioma
infection
inflammation

Additional relevant MeSH terms:
Disease
Infection
Communicable Diseases
Hypertension
Schizophrenia
Inflammation
Pneumonia
Epilepsy
Migraine Disorders
Bipolar Disorder
Thrombosis
Headache
Seizures
Urinary Tract Infections
Meningitis
Respiratory Tract Infections
Retinitis
Adenoviridae Infections
Angina, Stable
Herpes Simplex
Autistic Disorder
Hemangioma
Intraabdominal Infections
Adrenal Insufficiency
Cytomegalovirus Retinitis
Hemangioma, Capillary
Port-Wine Stain
Sepsis
Toxemia
Meningitis, Bacterial


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