Phase 1 PK/PD and Safety Study
We conducted an open-label, single-arm, two-period, fixed sequential-dose study to evaluate the PK, PD and safety of SP-102 (SEMDEXA™) when administered by epidural injection. SP-102 (SEMDEXA™) was compared to intravenous dexamethasone sodium phosphate injection in subjects with lumbosacral radiculopathy. There were 12 subjects enrolled in this study, all of whom received SP-102 (SEMDEXA™) followed by the intravenous dexamethasone sodium phosphate injection (Reference Listed Drug (“RLD”)) administered one month later. A RLD is an approved drug product to which new versions are compared to show that they are bioequivalent.
The purpose of this study was to establish the pharmaceutical bridge between SP-102 (SEMDEXA™) and the RLD. The Tmax observed with the administration of SP-102 (SEMDEXA™) was four hours, compared to 15 minutes observed with intravenous dexamethasone. The PD parameters and safety results of both products were similar, and SP-102 (SEMDEXA™) did not prolong cortisol suppression time. SP-102 (SEMDEXA™) also maintained analgesic effects throughout a one-month observation period.
The overall systemic exposure of dexamethasone was similar, whether administered as SP-102 (SEMDEXA™) or injected intravenously, with a mean AUCinf of 0.916 µg*h/mL (observed with SP-102 (SEMDEXA™)) compared to 0.943 µg*h/mL (observed with intravenously-administered dexamethasone). Notably, there was a 16-fold increase in the time to maximum serum concentration (“Tmax”) following epidural injection of SP-102 (SEMDEXA™). The median Tmax was 4.00 hours for SP-102 (SEMDEXA™) compared to 0.25 hours for the comparison group.
All 12 subjects with sciatica showed continuous reduction in back and leg pain during the one-month observation period following a single epidural injection of SP-102 (SEMDEXA™).
This study demonstrated that at an equivalent initial dose of dexamethasone, the systemic exposure to dexamethasone following epidural injection of SP-102 (SEMDEXA™) did not exceed the exposure following intravenous injection of the RLD. The PD effects, measured as white blood cell count, cortisol levels and glucose levels, as well as the safety profile, were similar between the two treatments. SP-102 (SEMDEXA™) injections were generally well tolerated and did not result in new unexpected side effects.
SP-102 (SEMDEXA) Pharmacokinetic Bridging Trial
- Epidural SP-102 injection was well tolerated
- Not associated with greater systemic dexamethasone exposure than IV dexamethasone at the same dose 10 mg (Reference Listed Drug)
Equivalent AUC - Lower mean plasma Cmax (~ 50% lower)
- Both treatments had similar PD effects on cortisol suppression, blood glucose, and WBC levels.
- Trial supports 505(b)(2) NDA, bridging to known systemic safety of FDA approved IV dose.
