109: A Comparison of Capillary Microsampling Devices Vs Venipuncture in a Single-Dose Clinical Pharmacokinetics Study of Large & Small Molecules

Statement of Purpose: The objective of this study was to compare the clinical pharmacokinetics of a diverse set of large and small molecules, from samples generated using conventional venipuncture vs two capillary microsampling devices collecting either liquid blood (Tasso+) or dry blood (Neoteryx Mitra).

Description of Methods & Materials: This was a single-dose study that enrolled four cohorts of ten healthy subjects each, A: crenezumab (15 mg/kg, IV), B: etrolizumab (210 mg, SC), C: GDC-X (30 mg, PO) and D: hydroxychloroquine (200 mg, PO). The bioanalytical methods used for the two monoclonal antibodies (mAbs) were Gyros or ELISA, with calibration and quality control samples prepared in serum matrix. LC-MS/MS was the bioanalytical method used for the two small molecules, with calibration and quality control samples prepared either in plasma or on the dried blood device. Baseline hematocrit level measured for each subject was applied as a correction factor to the concentrations of mAbs determined from the Mitra samples, whereas a blood/plasma partitioning ratio (B/P) was explored as a correction factor for the two small molecules.

Data & Results: For crenezumab and etrolizumab, the individual pharmacokinetic profiles obtained from venipuncture samples were comparable with those generated with Tasso+ and Mitra devices. For the two mAbs, the geometric mean ratio (GMR) for both C_max and AUC_t was between 0.8-1.25. For GDC-X, the individual PK profiles from venipuncture and Tasso+ were comparable, with a GMR between 0.8-1.25 for C_max and AUC_t. The individual concentrations of GDC-X and the mean AUC_t obtained from the Mitra samples were ~0.6 fold of plasma, which correlated with a known in vitro B/P of < 1. Hydroxychloroquine has a very high reported B/P of 5-16. In our study, the individual concentrations and the mean AUC_t of hydroxychloroquine from the Mitra device were ~13-fold higher than venipuncture. Surprisingly, the capillary plasma samples obtained with the Tasso+ device showed a consistent 3.5-fold higher concentration than venipuncture in all subjects at all time points.

Interpretation, Conclusion or Significance: In conclusion, the PK parameters of both mAbs derived from either Tasso+ serum or Mitra dry blood were comparable with venipuncture results. For GDC-X, a small molecule with B/P < 1, the plasma PK parameters matched well between Tasso+ and venipuncture. The AUC_t ratio determined from Mitra dry blood samples versus venipuncture plasma samples correlated with the respective B/P for both small molecules. These conclusions indicate that both microsampling devices can be readily deployed in clinical PK studies of mAbs, and the Tasso+ plasma device may be more suitable for small molecule PK studies in the absence of in vivo B/P data. The Mitra dry blood device can also be a viable option if B/P is evaluated prior to implementation.

Disclosures: Acknowledgments: Janis Allen, Emilia Calderon, Olga Carvalho, Brian Dean, Michael Dolton, Rebecca Elliott, Geralynn Gamboa, Vikram Malhi, Luna Musib, Rebecca Sheng, Mary Simon, Winnie Tse, Jesse Yu, Wenhui Zhang