The pharmacokinetics and pharmacodynamics of dexamethasone following epidural SP-102 or intravenous dexamethasone sodium phosphate injection in subjects with lumbosacral radicular pain

Objectives: To evaluate the pharmacokinetics, pharmacodynamics (PD), safety, and tolerability of epidural SP-102 (10 mg dexamethasone sodium phosphate injectable gel) compared to an intravenous injection of 10 mg dexamethasone sodium phosphate, USP (IV USP). Materials and methods: Subjects with lumbosacral radiculopathy received a single dose of epidural SP-102, followed by a single dose of IV USP 4 weeks later. Dexamethasone plasma levels, cortisol levels, white blood cells (WBC), and blood glucose levels were assessed. Results: Twelve subjects entered and completed the study. The mean total dexamethasone exposure (AUC(last) and AUC(inf)) following SP-102 by epidural injection was equivalent to the total exposure following IV USP. A lower mean plasma C-max. (similar to 50% lower) was observed following epidural administration compared to IV injection. PD parameters were similar between treatments. Adverse events (AEs) were mild, with no serious AEs or study discontinuations due to AEs. Conclusion: In this small study, epidural SP-102 injection was well tolerated, was not associated with greater systemic dexamethasone exposure than IV USP, and both treatments had similar PD effects on cortisol suppression, blood glucose, and WBC levels. What is known about this subject Epidural steroid injections (ESIs), the current standard of care, are not approved by the Food and Drug Administration (FDA) for managing lumbosacral radicular pain. SP-102 is being developed to address the serious complications associated with ESIs. SP-102 is a sterile dexamethasone sodium phosphate viscous gel solution of 10 mg dexamethasone for epidural administration. It does not contain neurotoxic preservatives or surfactants and is particulate-free, which is anticipated to reduce the risk of embolic events in case of inadvertent intra-arterial uptake during epidural injection. The viscous gel formulation was also designed to prolong the dexamethasone absorption at the injection site. There is no known published literature on the PK-PD and safety profiles of an epidural viscous dexamethasone gel. What this study adds This study was conducted to understand the preliminary PK-PD characteristics and safety profile of an epidural dexamethasone drug product, SP-102.