Patient Centric Microsampling to Support Paxlovid Clinical Development: Bridging and Implementation

Abstract

Nirmatrelvir is a potent and selective severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) main protease inhibitor. Nirmatrelvir co‐packaged with ritonavir (as PAXLOVID) received US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) on December 22, 2021, as an oral treatment for coronavirus disease 2019 (COVID‐19) and subsequent new drug application approval on May 25, 2023. Pharmacokinetic (PK) capillary blood sampling at‐home using Tasso‐M20 micro‐volumetric sampling device was implemented in the program, including three phase II/III outpatient and several clinical pharmacology studies supporting the EUA. The at‐home sampling complemented venous blood sampling procedures to enrich the PK dataset, to decrease the need for patients' site visit for PK sampling, and to allow different sampling approaches for flexibility and convenience. To demonstrate concordance/equivalence, bridging between venous plasma and Tasso dried blood results was conducted by comparing concentrations and derived PK parameters from both sampling approaches. In addition, a two‐compartment population PK model was utilized to bridge the plasma and Tasso data by estimating the PK parameters using blood‐to‐plasma ratio as a slope parameter. Operational challenges were successfully managed to implement at‐home PK sampling in global phase II/III trials. Sample quality was generally very good with less than 3% samples deemed as “not usable” from over 800 samples collected in all the studies. Experience gained from sites and patients will guide future broader implementations.