Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

Hypertension Clinical Trial

— PTN_POPS  

Official title:

Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01431326
• Other study ID #: Pro00029638
• Secondary ID: IND 113645IND 11
• Status: Completed
• Start date: November 2011
• Est. completion date: November 2019

Study information

• Verified date: August 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3520
• Est. completion date: November 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus
• Anesthesia
• Anxiety
• Anxiolysis
• Arrhythmias, Cardiac
• Autism
• Autistic Disorder
• Bacterial Meningitis
• Bacterial Septicemia
• Benzodiazepine
• Bipolar Disorder
• Bone and Joint Infections
• Bradycardia
• Cardiac Arrest
• Cardiac Arrhythmia
• Central Nervous System Infections
• Chronic Kidney Diseases
• CMV Retinitis
• Communicable Diseases
• Convulsions
• Cytomegalovirus Retinitis
• Early-onset Schizophrenia Spectrum Disorders
• Endocarditis
• Epilepsy
• Fibrinolytic Bleeding
• General Anesthesia
• Gram-negative Infection
• Gynecologic Infections
• Headache
• Healthcare-Associated Pneumonia
• Heart Failure
• Heavy Menstrual Bleeding
• Hemangioma
• Hemangioma, Capillary
• Hemophilia
• Hemophilia A
• Hemorrhage
• Herpes Simplex
• Herpes Simplex Virus
• Hyperaldosteronism
• Hyperkinesis
• Hypertension
• Hypokalemia
• Infantile Hemangioma
• Infection
• Infections
• Inflammation
• Inflammatory Conditions
• Insomnia
• Intra-abdominal Infections
• Intraabdominal Infections
• Kidney Diseases
• Lower Respiratory Tract Infections
• Meningitis
• Meningitis, Bacterial
• Menorrhagia
• Methicillin Resistant Staphylococcus Aureus
• Migraines
• Muscle Cramp
• Neuromuscular Blockade
• Neutropenia
• Nosocomial Pneumonia
• Pain
• Pneumonia
• Port-Wine Stain
• Pulmonary Arterial Hypertension
• Renal Insufficiency, Chronic
• Respiratory Tract Infections
• Retinitis
• Schizophrenia
• Sedation
• Seizures
• Sepsis
• Skeletal Muscle Spasms
• Skin and Skin-structure Infections
• Spasm
• Staphylococcal Infections
• Toxemia
• Treatment-resistant Schizophrenia
• Urinary Tract Infections
• Withdrawal

Intervention

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

Locations

Country	Name	City	State
Canada	Hospital Sainte-Justine	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	Manitoba Institute of Child Health	Winnipeg	Manitoba
Israel	Schneider Children's Medical Center of Israel	Petah Tikva
Israel	Assaf Harofeh Medical Center	Zerifin	Tel Aviv
Singapore	KK Women's and Children's Hospital Pte Ltd	Singapore
United Kingdom	Alder Hey Children's Hospital	Liverpool	Merseyside
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United States	University of New Mexico, Health Sciences Center	Albuquerque	New Mexico
United States	Alaska Native Medical Center	Anchorage	Alaska
United States	The Children's Hospital Colorado	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	University of Vermont Medical Center	Burlington	Vermont
United States	UNC Hospital Neonatal-Perinatal Medicine	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Children's Hospital	Charlottesville	Virginia
United States	Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Akron Children's Hospital	Cleveland	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of South Carolina	Columbia	South Carolina
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke University Medical Center (PICU / NICU)	Durham	North Carolina
United States	University of Kansas Medical Center	Fairway	Kansas
United States	Kapiolani Womens and Childrens Medical Center	Honolulu	Hawaii
United States	Riley Hospital for Children at Indiana University	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Florida Jacksonville Shands Medical Center	Jacksonville	Florida
United States	Children's Mercy Hospital and Clinics	Kansas City	Kansas
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	University of California at San Diego Medical Center	La Jolla	California
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Axis Clinical Trials	Los Angeles	California
United States	University of California, Los Angeles Medical Center	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Montana	Missoula	Montana
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Yale New Haven Children's Hospital	New Haven	Connecticut
United States	Ochsner Baptist Clinical Trials Unit	New Orleans	Louisiana
United States	Tulane University Health Science Center	New Orleans	Louisiana
United States	Board of Regents of the University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Utah Hospitals and Clinics	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia
United States	Wesley Medical Center	Wichita	Kansas
United States	Alfred I. DuPont Hospital for Children	Wilmington	Delaware

Sponsors (3)

Lead Sponsor	Collaborator
Daniel Benjamin	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Singapore,  United Kingdom, 

References & Publications (22)

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 — View 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 Hydrochlorothiaz — View 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 s — View 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 infan — View 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. Popul — View 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 — View 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 — View 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 Admin — View 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 Networ — View 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 Rel — View 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 an — View 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 Commi — View 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.202 — View 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 — View 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: 10.10 — View 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. d — View 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 — View 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 In — View 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 Clind — View 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. Po — View 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 N — View 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 Tri — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Data will be collected throughout the hospital or outpatient stay up to 90 days
Secondary	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.	Data will be collected throughout the hospital or outpatient stay up to 90 days
Secondary	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.	Data will be collected throughout the hospital or outpatient stay up to 90 days

External Links

•   Understudied Drugs Project Summary