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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01431326




Registration number
NCT01431326
Ethics application status
Date submitted
17/08/2011
Date registered
7/09/2011
Date last updated
2/04/2018

Titles & IDs
Public title
Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
Scientific title
Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
Secondary ID [1] 0 0
IND 113645
Secondary ID [2] 0 0
Pro00029638
Universal Trial Number (UTN)
Trial acronym
PTN_POPS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adenovirus 0 0
Anesthesia 0 0
Anxiety 0 0
Anxiolysis 0 0
Autism 0 0
Autistic Disorder 0 0
Bacterial Meningitis 0 0
Bacterial Septicemia 0 0
Benzodiazepine 0 0
Bipolar Disorder 0 0
Bone and Joint Infections 0 0
Central Nervous System Infections 0 0
Convulsions 0 0
Cytomegalovirus Retinitis 0 0
Early-onset Schizophrenia Spectrum Disorders 0 0
Epilepsy 0 0
General Anesthesia 0 0
Gynecologic Infections 0 0
Herpes Simplex Virus 0 0
Infantile Hemangioma 0 0
Infection 0 0
Inflammation 0 0
Inflammatory Conditions 0 0
Intra-abdominal Infections 0 0
Lower Respiratory Tract Infections 0 0
Migraines 0 0
Pain 0 0
Pneumonia 0 0
Schizophrenia 0 0
Sedation 0 0
Seizures 0 0
Skeletal Muscle Spasms 0 0
Skin and Skin-structure Infections 0 0
Thromboprophylaxis 0 0
Thrombosis 0 0
Treatment-resistant Schizophrenia 0 0
Urinary Tract Infections 0 0
Withdrawal 0 0
Sepsis 0 0
Gram-negative Infection 0 0
Bradycardia 0 0
Cardiac Arrest 0 0
Cardiac Arrhythmia 0 0
Staphylococcal Infections 0 0
Nosocomial Pneumonia 0 0
Neuromuscular Blockade 0 0
Methicillin Resistant Staphylococcus Aureus 0 0
Endocarditis 0 0
Neutropenia 0 0
Headache 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Mental Health 0 0 0 0
Schizophrenia
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Clotting disorders
Mental Health 0 0 0 0
Other mental health disorders
Mental Health 0 0 0 0
Depression
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Cardiovascular 0 0 0 0
Coronary heart disease
Blood 0 0 0 0
Other blood disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Eye 0 0 0 0
Diseases / disorders of the eye
Skin 0 0 0 0
Other skin conditions
Mental Health 0 0 0 0
Autistic spectrum disorders
Cardiovascular 0 0 0 0
Normal development and function of the cardiovascular system
Injuries and Accidents 0 0 0 0
Poisoning

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Treatment: Drugs - The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:

Treatment: Drugs: The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of pharmacokinetic outcomes for understudied drugs in children - 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.
Timepoint [1] 0 0
Data will be collected throughout the hospital or outpatient stay up to 90 days
Secondary outcome [1] 0 0
Composite pharmacodynamic outcomes of understudied drugs in children - 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.
Timepoint [1] 0 0
Data will be collected throughout the hospital or outpatient stay up to 90 days
Secondary outcome [2] 0 0
Biomarkers associated with understudied drugs in children - 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.
Timepoint [2] 0 0
Data will be collected throughout the hospital or outpatient stay up to 90 days

Eligibility
Key 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
Minimum age
No limit
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 1) Failure to obtain consent/assent (as indicated)

- 2) Known pregnancy as determined via interview or testing if available.

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Kids Research Institute - Randwick
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Hawaii
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Kentucky
Country [14] 0 0
United States of America
State/province [14] 0 0
Louisiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Maryland
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Mississippi
Country [18] 0 0
United States of America
State/province [18] 0 0
Missouri
Country [19] 0 0
United States of America
State/province [19] 0 0
Montana
Country [20] 0 0
United States of America
State/province [20] 0 0
Nebraska
Country [21] 0 0
United States of America
State/province [21] 0 0
New Hampshire
Country [22] 0 0
United States of America
State/province [22] 0 0
New Mexico
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Ohio
Country [25] 0 0
United States of America
State/province [25] 0 0
Oklahoma
Country [26] 0 0
United States of America
State/province [26] 0 0
Oregon
Country [27] 0 0
United States of America
State/province [27] 0 0
Rhode Island
Country [28] 0 0
United States of America
State/province [28] 0 0
South Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
Utah
Country [30] 0 0
United States of America
State/province [30] 0 0
Vermont
Country [31] 0 0
United States of America
State/province [31] 0 0
Virginia
Country [32] 0 0
United States of America
State/province [32] 0 0
Washington
Country [33] 0 0
United States of America
State/province [33] 0 0
West Virginia
Country [34] 0 0
United States of America
State/province [34] 0 0
Wisconsin
Country [35] 0 0
Canada
State/province [35] 0 0
Manitoba
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
Israel
State/province [38] 0 0
Tel Aviv
Country [39] 0 0
Israel
State/province [39] 0 0
Petah Tikva
Country [40] 0 0
Singapore
State/province [40] 0 0
Singapore
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Hampshire
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Merseyside
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Bristol

Funding & Sponsors
Primary sponsor type
Other
Name
Daniel Benjamin
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
The EMMES Corporation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/show/NCT01431326
Trial related presentations / publications
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.
Munzenberger PJ, Massoud N. Pharmacokinetics of gentamicin in neonatal patients supported with extracorporeal membrane oxygenation. ASAIO Trans. 1991 Jan-Mar;37(1):16-8.
Hoie EB, Swigart SA, Leuschen MP, Willett LD, Bolam DL, Goodrich PD, Bussey ME, Nelson RM Jr. Vancomycin pharmacokinetics in infants undergoing extracorporeal membrane oxygenation. Clin Pharm. 1990 Sep;9(9):711-5.
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.
Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muoio DM, Newgard CB. Metabolomics applied to diabetes research: moving from information to knowledge. Diabetes. 2009 Nov;58(11):2429-43. doi: 10.2337/db09-0580.
Laiakis EC, Morris GA, Fornace AJ, Howie SR. Metabolomic analysis in severe childhood pneumonia in the Gambia, West Africa: findings from a pilot study. PLoS One. 2010 Sep 9;5(9). pii: e12655. doi: 10.1371/journal.pone.0012655.
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Public notes

Contacts
Principal investigator
Name 0 0
Michael Cohen-Wolkowiez, MD
Address 0 0
Duke University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Barrie Harper, MT (ASCP), PMP
Address 0 0
Country 0 0
Phone 0 0
919-668-8291
Fax 0 0
Email 0 0
barrie.harper@duke.edu
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable