A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials

Authors: Dockendorf M, Jaworowicz DJ, Humphrey RL, Anderson M, Breidinger S, Kantesaria B, Bateman K, Woolf E, Stone J
Conference: ACoP
Keywords: Dried blood spot (DBS) pharmacokinetic (PK) sampling, Merck & Co., pop PK model
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background and Objectives

• Dried blood spot (DBS) pharmacokinetic (PK) sampling was investigated as a potential alternative to plasma sampling for Phase 3 verubecestat (MK-8931) trials due to several potential advantages (ie, reduced cost, reduced clinical site burden, and lower blood volume requirements)
• Following initial evaluations from simultaneously sampled DBS and plasma concentrations in the verubecestat EPOCH trial (P017), prespecified criteria to proceed with DBS as the PK matrix were met. Plasma sampling was discontinued, and DBS was intended as the sole PK matrix for the remainder of the trial

  • Subsequently, a stability issue with DBS emerged, necessitating re-examination of the planned DBS-plasma bridging approach (Figures 1 and 2)
  • A conversion algorithm for calculating plasma-equivalent concentrations from DBS concentrations, accounting for sample stability, was developed to enable verubecestat population PK (pop PK) analysis from pooled plasma and DBS samples

Ninth American Conference on Pharmacometrics (ACoP) Annual Meeting, October 6-12, 2018, San Diego, CA

By Marissa F. Dockendorf, David Jaworowicz, Rebecca Humphrey, Melanie Anderson,  Sheila Breidinger, Bhavna Kantesaria, Kevin P. Bateman, Eric Woolf, Julie Stone