SAT0202 Comparison of the bioavailability of a single dose of certolizumab pegol injected by pre-filled syringe or by electro-mechanical auto-injection e-device: a phase 1, open-label, randomised, parallel group, single-centre bioequivalence study
Authors: R. Oliver, B. VanLunen, I. Mountian, E. Brown, D. Tatla
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> When administered subcutaneously (SC) using a pre-filled syringe (PFS), the anti-TNF certolizumab pegol (CZP) has a half-life of ~14 days and has shown good bioavailability (~80%) at all tested doses in healthy volunteers and patients with rheumatoid arthritis.<sup>1,2</sup> A reusable electro-mechanical auto-injection device (e-Device), ava<sup>®</sup>, was recently approved in the EU,<sup>1</sup> providing an alternative SC-delivered CZP option in addition to the PFS and autoinjector device (AutoClicks<sup>®</sup>).<sup>1,3</sup> <h3>Objectives:</h3> To determine if a single 200 mg CZP dose is bioequivalent when delivered SC by PFS or e-Device, and to assess the safety and tolerability of both administration methods. <h3>Methods:</h3> NCT02806219 was a phase 1, open-label, randomized, parallel group, single-center bioequivalence study. Healthy volunteers were randomized 1:1 to receive CZP via either the PFS or e-Device. Primary outcomes were assessed using the pharmacokinetic per-protocol set (PK-PPS): maximum CZP plasma concentration (C<sub>max</sub>), area under the plasma concentration vs time curve (AUC), and AUC from baseline (BL) to final data point (AUC<sub>(0-t)</sub>). At BL (Day 1), volunteers received a single 200 mg CZP dose. CZP plasma concentrations were measured on Day 1 prior to CZP administration, at 12 hours (h) post-dose, and on Days 2–7, 10, 14, 21, 28, 42, 56, and 70. Safety and tolerability were assessed using the safety set (all receiving a CZP dose) via reported treatment-emergent adverse events (TEAEs), serious AEs, and adverse device events (ADEs: AEs considered by the investigator to be related to/caused by the device). An injection site pain visual analog scale (VAS; 0–100 mm) was completed immediately post-injection (0 h) and 1 h post-injection. <h3>Results:</h3> 100 healthy volunteers were randomized to receive CZP either via PFS (n=50) or e-Device (n=50). The mean plasma CZP concentration vs time profiles for the e-Device and PFS were comparable. Point estimates and 90% confidence intervals (CIs) for test/reference geometric mean ratios in C<sub>max</sub> and AUC were contained within bioequivalence limits of 80–125% (table 1). Both administration methods were equally well tolerated; all reported TEAEs were mild or moderate, with no ADEs or injection site reaction TEAEs. Mean VAS pain scores were low at 0 h (PFS: 10.7 [SD 14.3], e-Device: 18.0 [24.4]) and 1 h (1.4 [2.9] vs 2.7 [7.0]). <h3>Conclusions:</h3> CZP 200 mg doses were bioequivalent whether administered by PFS or e-Device. The SC-delivered CZP injections were well tolerated in healthy volunteers when using either method. <h3>References</h3> [1]EMA. Summary of Product Characteristics (Cimzia)2017. [2]Choy EHS, et al. Rheumatology (Oxford)2002;41:1133–7. [3]Astruc B, et al. Ann Rheum Dis2016;75:1003(AB0301). <h3>Acknowledgements:</h3> This study was funded by UCB Pharma. We thank the healthy volunteers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical. <h3>Disclosure of Interest:</h3> R. Oliver Employee of: UCB Pharma, B. VanLunen Employee of: UCB Pharma, I. Mountian Employee of: UCB Pharma, E. Brown Employee of: UCB Pharma, D. Tatla Employee of: UCB Pharma