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

Nirmatrelvir is a potent and selective SARS-CoV-2 main protease inhibitor. Nirmatrelvir co-packaged with ritonavir (as PAXLOVID TM ) received FDA Emergency Use Authorization (EUA) on 22 Dec 2021 as an oral treatment for COVID-19 and subsequent NDA approval on 25 May 2023. PK capillary blood sampling at-home using Tasso-M20 micro-volumetric sampling device was implemented in the program, including three Phase 2/3 out-patient 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 pharmacokinetic parameters from both sampling approaches. In addition, a 2-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 2/3 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.