Background: The pharmacokinetics of drugs excreted by the kidneys may be altered by renal (kidney) impairment, requiring dosing adjustments. However, the majority of drugs that are predominantly renally excreted and have dosage recommendations for adults with renal impairment lack dose adjustment recommendations for pediatric patients with renal impairment. This is largely due to the lack of generation of pharmacokinetic data in pediatric patients with renal impairment, which is attributable to both the ethical and the practical limitations of conducting dedicated renal impairment studies in pediatric patients, as well as the exclusion of pediatric patients with renal impairment from most clinical efficacy and safety studies. For drugs that are renally cleared, exposures can be impacted by both the maturation of kidney function and the renal impairment due to kidney disease.
The main objective of the ‘‘Advancing the Development of Pediatric Therapeutics (ADEPT 8) on Drug Dosing in Pediatric Patients With Renal Impairment’’ workshop is to discuss current approaches to classifying renal impairment in the pediatric population, identify data gaps, and explore scientifically supported approaches and methods for providing information on dosing adjustment. The workshop will specifically focus on measurements of renal function, extrapolation of adult data, and approaches to generating clinical trial data to assess the impact of renal impairment on the pharmacokinetics of drugs in pediatric patients. In addition, the workshop will allow for an open dialogue around the use of these approaches among regulators, industry, academia, and patient organizations.
The purpose of the public workshop is to discuss the current landscape of drug dosing in pediatric patients with renal impairment, understand the gaps in knowledge, and consider innovative approaches to improve the current paradigm for dosing in pediatric patients with renal impairment.
ADEPT 8: Workshop on drug dosing in Pediatric Patients with Renal Impairment
Thursday, November 30, 2023
Link to the PDF Workshop Presentations
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9:00 - 9:05 a.m.
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Welcome - Lily Mulugeta (FDA) and Bakri Alzarka (Univ. of Maryland) |
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| 9:05 - 9:15 a.m. |
Introductory remarks - FDA
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| 9:15 - 9:25 a.m. |
Setting the scene - Shamir Tuchman (FDA)
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| 9:25 a.m. - 9:35 a.m. |
Opening presentation - Martina Sahre (FDA)
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| 9:35 a.m. - 9:45 a.m. |
Drug clearance in pediatric patients with renal impairment - Saskia de Wildt (Radboud Univ. Medical Center)
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| 9:45 a.m. - 9:55 a.m. |
Case example: Avycaz (Abbvie) - Henrietta Abodakpi (FDA)
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Session 1: What constitutes as renal impairment in pediatric patients for the purposes of PK characterization and drug dosing? (RECORDINGS)
Academic Perspective: Considerations around assessment of renal function
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| 9:55 a.m. - 10:10 a.m. |
Strengths and limitations of existing estimation methods and applications to specific population - George Schwartz (Univ. of Rochester Medical Center)
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| Clinical Perspective: Considerations around assessment of renal function and drug dosing |
Clinical Perspective: Considerations around assessment of renal function and drug dosing
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| 10:10 a.m. - 10:30 a.m. |
What clinicians and other stakeholders need to know about special populations
Guido Filler (Western Univ. – London, Ontario, Canada; Children's Hospital, London Health Sciences Centre)
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| Industry Perspective: Considerations around assessment of renal function in the context of clinical trial |
Industry Perspective: Considerations around assessment of renal function in the context of clinical trial
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| 10:30 a.m. - 10:45 a.m. |
Speaker 1: Ashish Sharma (Boehringer-Ingelheim)
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| 10:45 a.m. - 11:10 a.m. |
Speakers 2 and 3: Nicholas Webb and Deepa Chand (Novartis) |
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| 11:10 a.m. - 11:30 a.m. |
BREAK |
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| 11:30 a.m. - 1:00 p.m. |
Moderated Panel Discussion and Q&A
Moderators: Mona Khurana (FDA) and Bakri Alzarka (Univ. of Maryland)
Panelists:
• Shamir Tuchman (FDA)
• Martina Sahre (FDA)
• Deepa Chand (Novartis; Univ. of Illinois College of Medicine)
• Nicholas Webb (Novartis)
• Afshin Parsa (NIH)
• George Schwartz (Univ. of Rochester Medical Center)
• Guido Filler (Western Univ. – London, Ontario, Canada)
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| 1:00 - 2:00 p.m. |
LUNCH |
LUNCH |
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Session 2: Translating adult renal impairment data in pediatric patients with renal impairment (RECORDINGS)
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| 2:00 p.m. - 2:10 p.m. |
Recap of Case Example: Avycaz (Abbie) - Henrietta Abodakpi (FDA)
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| 2:10 p.m. - 2:25 p.m. |
Translating adult renal impairment PK data Academic/clinical perspective Saskia de Wildt (Radboud Univ. Medical Center)
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| 2:40 p.m. - 4:30 p.m. |
Moderated Panel Discussion and Q&A
Moderators: Lily Mulugeta (FDA) and Tsuyoshi Fukuda (Eli Lilly)
Panelists:
• Lynne Yao (FDA)
• Martina Sahre (FDA)
• Vikram Sinha (Novartis)
• Rebecca Wrishko (Merck)
• Saskia de Wildt (Radboud Univ. Medical Center)
• George Schwartz (Univ. of Rochester Medical Center)
• Jeff Barrett (Aridhia)
• Thomas Nolin (Univ. of Pittsburgh School of Pharmacy)
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| 4:30 - 4:40 p.m. |
Summary and closing - Lily Mulugeta (FDA) and Bakri Alzarka (UMD
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Friday, December 1, 2023
Link to the PDF Workshop Presentations
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Session 3: Future Directions: Dosing in pediatric patients with renal impairment (RECORDINGS)
Role of modeling and simulation
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| 9:00 a.m. - 9:10 a.m. |
Considerations for modeling and simulation for pediatric renal impairment - Justin Earp (FDA)
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| 9:10 a.m. - 9:20 a.m. |
Role of systems biology modeling in extrapolating efficacy and safety from adult renal impairment data – Karim Azer (Rutgers Univ.)
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| 9:20 a.m. - 10:30 a.m. |
Moderated Panel Discussion and Q&A
Moderators: Elimika Pfuma Fletcher (FDA) and Jeff Barrett (Aridhia)
Panelists:
• Jason Moore (FDA)
• Hao Zhu (FDA)
• Saskia de Wildt (Radboud Univ. Medical Center)
• Sonya Tang Girdwood (Cincinnati Children’s)
• Liping Zhang (Johnson & Johnson)
• Karim Azer (Rutgers Univ.)
• Efthymios Manolis (EMA)
• Pieter Colin (EMA)
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| 10:30 a.m. - 10:45 a.m. |
BREAK
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| 10:45 a.m. - 10:55 a.m. |
Industry perspective; Jan Marquard (Boehringer-Ingelheim) |
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| Labeling considerations |
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| 10:55 a.m. - 11:05 a.m. |
Su-Young Choi (FDA) |
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| 11:05 a.m. - 12:05 p.m. |
Moderated Panel Discussion and Q&A
Moderators: Lynne Yao (FDA) and Bakri Alzarka (Univ. of Maryland)
Panelists:
• Kirtida Mistry (FDA)
• Gil Burckart (FDA)
• Bradley Warady (Children’s Mercy Kansas City)
• Adam Levy (BMS Pediatric Center of Excellence)
• Ashish Sharma (Boehringer-Ingelheim)
• Jan Marquard (Boehringer-Ingelheim)
• Susan Mendley (NIH)
• Guido Filler (Western Univ; Children's Hospital, London Health Sciences Centre)
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| 12:05 - 12:15 p.m. |
Summary and Closing Remarks - Lynne Yao, FDA
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