Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)

Hypertension Clinical Trial

— POPS or POP02  

Official title:

Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04278404
• Other study ID #: Pro00103838
• Status: Recruiting
• Start date: March 5, 2020
• Est. completion date: July 2024

Study information

• Verified date: March 2024
• Source: Duke University
• Contact: Chi Hornik
• Phone: (919) 260-7626
• Email: chi.hornik[@]duke.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: July 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Adrenal Insufficiency
• Arrythmia
• Asthma in Children
• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Blood Coagulation Disorders
• Bronchopulmonary Dysplasia
• Coagulation Disorder
• Communicable Diseases
• Coronavirus Infection (COVID-19)
• Coronavirus Infections
• Down Syndrome
• Edema
• Fibrinolysis; Hemorrhage
• Heart Failure
• Hemophilia
• Hemorrhage
• Hemostatic Disorders
• Hyperaldosteronism
• Hyperphosphatemia
• Hypertension
• Hypokalemia
• Infections
• Insomnia
• Kawasaki Disease
• Menorrhagia
• Mucocutaneous Lymph Node Syndrome
• Multisystem Inflammatory Syndrome in Children (MIS-C)
• Pain
• Pneumonia
• Primary Hyperaldosteronism
• Pulmonary Arterial Hypertension
• Skin Infection
• Syndrome
• Urinary Tract Infections
• Urinary Tract Infections in Children

Intervention

Drug:
• The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
The prescribing of drugs to children is not part of this protocol. Participants will receive DOIs as prescribed by their treating provider.

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	University of New Mexico Health Science Center	Albuquerque	New Mexico
United States	Colorado University Denver	Aurora	Colorado
United States	The Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina Children's Hospital	Charleston	South Carolina
United States	Ann and Robert H. Lurie Childrens Hospital of Chicago	Chicago	Illinois
United States	Ann and Robert H. Lurie Childrens Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	University of South Carolina	Columbia	South Carolina
United States	University of Texas-Southwestern Medical Center Dallas	Dallas	Texas
United States	Duke University Health System	Durham	North Carolina
United States	Pennsylvania State University--Hershey Children's Hospital	Hershey	Pennsylvania
United States	Kapiolani Womens and Childrens Medical Center	Honolulu	Hawaii
United States	The Womens Hospital of Texas	Houston	Texas
United States	University of Texas--Memorial Hermann Texas Medical Center	Houston	Texas
United States	Riley Hospital for Children at Indiana University	Indianapolis	Indiana
United States	University of Iowa Stead Family Children's Hospital	Iowa City	Iowa
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	Kansas City	Missouri
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center-JG Kidney Institute	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Massachusetts General Hospital	Lexington	Massachusetts
United States	Arkansas Children's Hospital Research Institute	Little Rock	Arkansas
United States	University of California, Los Angeles Medical Center	Los Angeles	California
United States	University of Louisville Norton Childrens Hospital	Louisville	Kentucky
United States	Mississippi Center for Advanced Medicine	Madison	Mississippi
United States	University of Wisconsin	Madison	Wisconsin
United States	University Wisconsin Madison	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
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	Lucile Packard Children's Hospital	Palo Alto	California
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Avera McKennan Hospital & University Medical Center	Sioux Falls	South Dakota
United States	Alfred I. DuPont Hospital for Children	Wilmington	Delaware

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	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, 

References & Publications (11)

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. — 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 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. — 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 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. — 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 Chemother. 2016 Apr 22;60(5):2888-94. doi: 10.1128/AAC.03086-15. Print 2016 May. — 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 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. — 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 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. — 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 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. — 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 and Intravenous Ketamine in Children. J Clin Pharmacol. 2018 Aug;58(8):1092-1104. doi: 10.1002/jcph.1116. Epub 2018 Apr 20. — 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 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. — 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 Neonates. Ther Drug Monit. 2018 Feb;40(1):103-108. doi: 10.1097/FTD.0000000000000466. — 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 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling		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.
Primary	Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling		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.
Primary	Elimination rate constant (ke) as measured by PK sampling		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.
Primary	Half-life (t1/2) as measured by PK sampling		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.
Primary	Absorption rate constant (ka) as measured by PK sampling		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.
Primary	AUC (area under the curve) as measured by PK sampling		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.
Primary	Maximum concentration (Cmax) as measured by PK sampling		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.
Primary	Time to achieve maximum concentration (Tmax) as measured by PK sampling		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.

External Links

•   Extracorporeal Life Support Organization (ELSO). ECLS Registry Report: International Summary Ann Arbor, MI: Extracorporeal Life Support Organization (ELSO); 2020
•   Food and Drug Administration. General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products
•   Wildschut E, editor. Drug therapies in neonates and children during extracorporeal membrane oxygenation (ECMO); Keep your eyes open. Rotterdam, The Netherlands: Erasmus MC; 2010.