Background Evaluation of the pharmacokinetic (PK) properties of certolizumab pegol (CZP) has shown a linear relationship between the dose administered (intravenous and subcutaneous [sc] routes), the maximum plasma concentration (Cmax), and the area under the plasma concentration versus time curve (AUC).1 In multiple clinical studies, the half-life (t1/2) was approximately 14 days for all CZP dosage levels tested. CZP has also been demonstrated to have good bioavailability (approximately 80%) when given sc.1
Objectives To compare the bioavailability of a single CZP 400 mg dose given as 2 x 200 mg injections injected by either a pre-filled syringe (PFS) or by an auto-injection device (AI), and to investigate the safety and tolerability of both methods of administration.
Methods In this open-label phase I study, healthy volunteers were randomized into two parallel groups. On Day 1, study participants were injected with either 2 x 200 mg CZP via a PFS or 2 x 200 mg CZP via an AI. CZP plasma concentrations were measured pre-dose, and post-dose at 12h, 24h and Days 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56 and 84. Safety and tolerability were assessed by recording adverse events (AEs) and serious AEs (SAEs). In addition, the tolerability of the injection was assessed by a pain visual analog scale (VAS) and an injection site reaction questionnaire.
Results 98 healthy volunteers were randomized to the PFS (n=49) and AI (n=49) groups. The mean plasma CZP concentration vs time profile of the AI was similar to that of the PFS. PK parameters were similar between the two modes of administration (Table). The 90% confidence intervals (CI) for the test/reference geometric mean ratios in Cmax, AUC(0-t), AUC and t1/2 were all contained in the bioequivalence range of 80–125%, and no statistically significant difference was found for tmax between the two modes of administration (Table). Safety assessments showed that both methods of administration were equally well-tolerated. Injections performed with the AI appeared to be less painful immediately after administration than injections given by the PFS, as well as being associated with less burning and redness.
Conclusions CZP 400 mg dose is bioequivalent whether administered by AI or PFS. Overall, CZP injections were safe and well-tolerated for both administration methods.
EMA. Summary of Product Characteristics (Cimzia) 2015
Acknowledgement The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance.
Disclosure of Interest B. Astruc Employee of: Biotrial, S. Watanabe Employee of: UCB Pharma, G. Parker Employee of: UCB Pharma, R. Hulhoven Employee of: UCB Pharma