Clinical trial NCT01431326: Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
Official title: Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adenovirus
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
Keywords: adenovirus
anaesthetic
anesthesia
anticoagulant
anti-epileptic
anti-inflammatory
antimicrobial
anti-psychotic
antiviral
anxiety
anxiolysis
anxiolytic
autism
autistic disorder
benzodiazepine
bipolar disorder
convulsions
epilepsy
headaches
herpes simplex virus
herpes simplex virus (HSV)
hypertension
infantile hemangioma
infection
inflammation
influenza
lower respiratory tract infection (LRTI)
meningitis
migraines
muscle spasms
pain
pneumonia
prophylaxis
retinitis
schizophrenia
sedation
sedative
seizures
septicemia
swelling
urinary tract infection
urinary tract infection (UTI)
withdrawal
empiric therapy
staphylococci
Fibrinolytic Bleeding
pulmonary arterial hypertension
CMV retinitis
control of serum phosphorus
Hyperaldosteronism
hypokalemia
heart failure
hemophilia
Heavy Menstrual Bleeding
insomnia
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: The Emmes Company, LLC
First posted: 2011-09-09
Enrollment: 3520
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children (\<21 years of age) receiving drugs per standard of care as prescribed by treating caregiver

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).

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 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.

Primary outcomes:
measure: Composite of pharmacokinetic outcomes for understudied drugs in children
timeFrame: Data will be collected throughout the hospital or outpatient stay up to 90 days
Secondary outcomes:
measure: Composite pharmacodynamic outcomes of understudied drugs in children
timeFrame: Data will be collected throughout the hospital or outpatient stay up to 90 days
measure: Biomarkers associated with understudied drugs in children
timeFrame: Data will be collected throughout the hospital or outpatient stay up to 90 days
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Native Medical Center
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: La Jolla
country: United States
facility: University of California at San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles Medical Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Children's Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I. DuPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida Jacksonville Shands Medical Center
state: Florida
city: Honolulu
country: United States
facility: Kapiolani Womens and Childrens Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Science Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Baptist Clinical Trials Unit
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Missoula
country: United States
facility: University of Montana
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico, Health Sciences Center
state: New Mexico
city: Chapel Hill
country: United States
facility: UNC Hospital Neonatal-Perinatal Medicine
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center (PICU / NICU)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Board of Regents of the University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Children's Hospital
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Winnipeg
country: Canada
facility: Manitoba Institute of Child Health
state: Manitoba
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hospital Sainte-Justine
state: Quebec
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
state: Tel Aviv
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital Pte Ltd
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
state: Merseyside
Study officials:
affiliation: Duke University
name: Chi Hornik, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.