Islatravir (ISL) MK-8591 is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) being studied for HIV-1 treatment and prevention. Following oral dosing, ISL is rapidly absorbed and is taken up into cells where it is phosphorylated to the active form of islatravir triphosphate (ISL-TP). Measuring the intracellular ISL-TP involves a multi-step isolation and stabilization process, which is typically only done at select phase 1 clinical sites. Multiple microsampling methods were tested in Phase 1 and correlation with ISL-TP was established. Microsampling was implemented with two different methods in phase 2 multi-site studies with a focus on generating exposure data otherwise not feasible to collect in late-stage studies and minimizing the burden on study participants. Microsampling dry blood measures total ISL, which includes plasma ISL as well as all of the intracellular ISL anabolites, including ISL-TP. Implementation of the two methods in multisite late-stage studies resulted in numerous implementation learnings and varying amounts of usable data. In preparation for the late-stage analyses, the phase 1 microsampling data were incorporated into the population PK model to link ISL plasma, intracellular ISL-TP, and microsampled total ISL. Implementation of microsampling allowed for the collection of additional exposure data in late-stage studies enhancing the exposure knowledge for modeling and simulation analyses and minimizing the burden to the participant.
Learning Objectives:
Understand key drug development questions that can be informed through microsampling
Understand the implementation of different patient centric sampling methods to address drug development questions
Understand some of the implementation learnings for late stage studies
