Using a population mechanistic TMDD model calibrated on preclinical monkey data to simulate first-in-human

Authors: Ayral G
Conference: SLP MIDD+
Software: Monolix®, Simulx®
Division: Lixoft

Challenges for First-in-human

Which dose to choose to elicit the desired effect (efficacy), without causing harm (safety)?

No Observable Adverse Effect Level:

  • Determine NOAEL dose in preclinical species
  • Scale to human based on body-weight or BSA
  • Add 10-fold safety margin

Minimal Anticipated Biological Effect Level:

  • Requires to understand the PD (biological effect)
  • PK/PD modeling can give valuable insight (e.g on receptor occupancy)

By Geraldine Ayral

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Presented at SLP MIDD+ Virtual Conference March 3-4, 2021