Clinical trial NCT04278404: Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)
Official title: Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Coronavirus Infection (COVID-19)
Pulmonary Arterial Hypertension
Urinary Tract Infections in Children
Hypertension
Pain
Hyperphosphatemia
Primary Hyperaldosteronism
Edema
Hypokalemia
Heart Failure
Hemophilia
Menorrhagia
Insomnia
Pneumonia
Skin Infection
Arrythmia
Asthma in Children
Bronchopulmonary Dysplasia
Adrenal Insufficiency
Fibrinolysis; Hemorrhage
Attention Deficit Hyperactivity Disorder
Multisystem Inflammatory Syndrome in Children (MIS-C)
Kawasaki Disease
Coagulation Disorder
Down Syndrome
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: The Emmes Company, LLC
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2020-02-20
Enrollment: 5000
Sex: ALL
Minimum age (years): 0
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children under 21 years of age.

Brief summary: The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.


Eligibility criteria: Inclusion Criteria:

1. Participant is \< 21 years of age
2. Parent/ Legal Guardian/ Adult Participant can understand the consent process and is willing to provide informed consent/HIPAA:
3. (a) Participant is receiving one or more of the study drugs of interest at the time of enrollment or (b) Participant is NOT receiving one or more of the study drugs of interest but is SARS-COV-2 positive within 60 days prior to enrollment

Exclusion Criteria:

1. Participant has a known pregnancy

   Below exclusion criteria apply only to:

   Participants receiving one or more of the study drugs of interest at the time of enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for details on enrollment cohort specifications and additional eligibility criteria)
2. Has had intermittent dialysis within previous 24 hours
3. Has had a kidney transplant within previous 30 days
4. Has had a liver transplant within previous 1 year
5. Has had a stem cell transplant within previous 1 year
6. Has had therapeutic hypothermia within previous 24 hours
7. Has had plasmapheresis within the previous 24 hours
8. Has a Ventricular Assist Device
9. Has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study

Primary outcomes:
measure: Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: Elimination rate constant (ke) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: Half-life (t1/2) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: Absorption rate constant (ka) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: AUC (area under the curve) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: Maximum concentration (Cmax) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
measure: Time to achieve maximum concentration (Tmax) as measured by PK sampling
timeFrame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Institute
state: Arkansas
city: Los Angeles
country: United States
facility: University of California, Los Angeles Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: Aurora
country: United States
facility: Colorado University Denver
state: Colorado
city: Aurora
country: United States
facility: The Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Alfred I. DuPont Hospital for Children
state: Delaware
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: Ann and Robert H. Lurie Childrens Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Childrens Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Stead Family Children's Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center-JG Kidney Institute
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Norton Childrens 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 Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Lexington
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
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 Science Center
state: New Mexico
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
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: Hershey
country: United States
facility: Pennsylvania State University--Hershey Children's Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina Children's Hospital
state: South Carolina
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera McKennan Hospital & University Medical Center
state: South Dakota
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Dallas
country: United States
facility: University of Texas-Southwestern Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas--Memorial Hermann Texas Medical Center
state: Texas
city: Houston
country: United States
facility: The Womens Hospital of Texas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
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: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Madison
country: United States
facility: University Wisconsin Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: Duke Clinical Research Institute
name: Chi Hornik
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: 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.
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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: 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: 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: 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.
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