Repeat Epidural Injections of SP-102 (Dexamethasone Sodium Phosphate Injectable Gel) in Subjects with Lumbosacral Radiculopathy

Abstract

Purpose: SP-102 is a novel epidural steroid injection (ESI) formulation of 10 mg dexamethasone sodium phosphate in a viscous gel solution. Repeat dosing of ESIs is possible if required for pain relief, but with consideration of hypothalamic-pituitary-adrenal (HPA) axis suppression from prolonged systemic exposure. This phase I/II study investigated the effect of initial and repeat SP-102 injections on HPA suppression and analgesia.

Methods: Subjects with lumbosacral radiculopathy received an initial epidural SP-102 injection (T1) on day 1, followed by a repeat injection (T2) on ≥28 days later. To determine HPA suppression, area under the effect curve over 28 days and maximum change from baseline were calculated for cortisol, glucose levels, and white blood cell (WBC) count. Equivalent effect on HPA suppression of T1 relative to T2 was determined if the 90% CIs for ratios of these measures were within 80%-125%. The effect of repeat injections on leg and back pain was also assessed.

Results: Based on the responder analysis, all subjects had achieved a cortisol response by day 3 after initial injection and by day 2 after repeat injection. The repeat injection had similar effects on glucose levels and WBC count to the initial injection. Pain scores decreased after each injection and remained low for the 28-day follow-up, with some evidence of improved analgesic effect of the second dose compared with the first. There were no serious adverse events or discontinuations due to adverse events.

Conclusion: The lack of cumulative effect and rapid resolution of HPA suppression following repeated SP-102 dosing suggests that consideration of HPA pharmacodynamics is not clinically relevant when making decisions regarding repeat dosing. SP-102 ESIs provided prolonged pain relief, with preliminary evidence of greater efficacy after repeat injection. A phase III trial is ongoing.

Clinical trial identifier: ClinicalTrials.gov: NCT03613662.

Keywords: epidural steroid injections; lubosacral radicuar pain; neuropathic pain; sciatica.

Conflict of interest statement

CA reports employment with Scilex Pharmaceuticals Inc during the study and outside the submitted work. ES reports receiving consultancy fees from Scilex Pharmaceuticals Inc during the study. DL reports employment with Scilex Pharmaceuticals Inc during the study and outside the submitted work. The authors report no other conflicts of interest in this work.

© 2021 Radnovich et al.

Figures

Figure 1

Pharmacodynamic assessments of single and repeat doses of SP-102. Pharmacodynamic assessments through 8 days after initial (T1) and repeat (T2) epidural injections. Mean cortisol levels over time (A), mean blood-glucose levels over time (B), mean WBC count over time (C). Error bars denote SD.

Figure 2

Analgesic effects of single and repeat doses of SP-102. Analgesic assessments after initial (T1) and repeat (T2) epidural injections. Mean NPRS score for average leg pain (A), mean BPI-SF pain-severity score (B), mean BPI-SF pain-interference score (C). Error bars denote SD.