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
Ruth Oliver,1 Brenda VanLunen,2 Irina Mountian,3 Erin Brown,2 Daljit Tatla2
1UCB Pharma, Slough, UK; 2UCB Pharma, Raleigh, NC, US; 3UCB Pharma, Brussels, Belgium
When administered subcutaneously (SC) using a pre-filled syringe (PFS), the anti-TNF certolizumab pegol (CZP) has a half-life of ~14 days and good bioavailability (~80%) at all tested doses. A reusable electro-mechanical auto-injection device (e-Device), ava®, was recently approved in the EU, providing an alternative SC-delivered CZP option in addition to the PFS and autoinjector device (AutoClicks®).
To determine if a single 200mg CZP dose is bioequivalent when delivered SC by PFS or e-Device, and to assess the safety and tolerability of both administration methods.
NCT02806219 was a phase 1, open-label, randomised, parallel group, single-centre bioequivalence study. Healthy volunteers were randomised 1:1 to receive 200mg CZP via a PFS or e-Device. Primary outcomes were maximum CZP plasma concentration (Cmax), area under the plasma concentration vs time curve (AUC), and AUC from baseline (BL) to final data point (AUC(0-t)). At BL (Day 1), volunteers received a single 200mg 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; 0–100mm) was completed post-injection (0h) and 1h post-injection.
100 healthy volunteers were randomised to 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 Cmax 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 0h (PFS: 10.7 [SD 14.3], e-Device: 18.0 [24.4]) and 1h (1.4 [2.9] vs 2.7 [7.0]).
CZP 200mg doses were bioequivalent whether administered by PFS or e-Device. The SC-delivered CZP injections were well tolerated when using either method.