Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

Conditions
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Hypokalemia, Migraines, 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, 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, Heart Failure, Hemophilia, Heavy Menstrual Bleeding, Insomnia

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypokalemia, 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, heart failure, hemophilia, Heavy Menstrual Bleeding, insomnia