Discussion: Sildenafil case C. Male, Paediatric Committee - - PowerPoint PPT Presentation

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Discussion: Sildenafil case C. Male, Paediatric Committee - - PowerPoint PPT Presentation

Apr 04, 2023 235 likes •282 views

Discussion: Sildenafil case C. Male, Paediatric Committee Similarity of disease? Similarity of response to treatment? - Pathophysiology; pharmacology - Historical data - Evolving data Discussion: Sildenafil case Pharmakokinetics:

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SLIDE 1

Discussion: Sildenafil case

  • Similarity of disease?
  • Similarity of response to treatment?
  • Pathophysiology; pharmacology
  • Historical data
  • Evolving data
  • C. Male, Paediatric Committee
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SLIDE 2

Discussion: Sildenafil case

Pharmakokinetics:

  • Could the initial dose-projection be improved
  • Physiology-based model
  • Separate PK study
  • Age-staggered approach
  • Dosing by weight categories (8-20; 20-45; >45kg) rather

than individual weight-adjusted dosing

  • high variability of actual doses and overlap between dose

categories

  • Analysis by actual doses/exposures?
  • Lack of age-appropriate formulation
  • Age-groups ignored
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SLIDE 3

Discussion: Sildenafil case

Endpoint correlations (translation):

Literature: 6MWT ~ morbidity & mortality (adults) Literature: CPET ~ morbidity & mortality (adults) Literature: 6MWT ~ CPET (some limitations) (adults and children) FDA/Sildenafil: 6MWT ~ PVRI (adults) Sildenafil: CPET ~ PVRI (children) ? 6MWT ~ PVRI adults = CPET ~ PVRI children ?? data in children unable for CPET ?

  • Approach generally supported but not all assumtions

validated

  • Measure further endpoints in parallel (TTCW, echo, BNP,

etc)

  • Further validation across several trials/drugs