Pharmacokinetic and Toxicology Studies
We conducted PK and toxicology studies in two non-rodent animal species to assess SP-102 (SEMDEXA™) administered via epidural and intrathecal routes with single and multiple dose regimens. Pharmacokinetically, a prolonged increase in the active dexamethasone metabolite was consistent with the extended residence time of the viscous gel formulation of SP-102 (SEMDEXA™) at the site of injection. There were no new unexpected toxicology findings apart from well-characterized toxicity findings commonly observed with administration of dexamethasone sodium phosphate.
SP-102 (SEMDEXA™) Toxicology GLP Study Summary
- No drug-related effects on any parameter: ECG, Clin obs, BW, Neurology, Clinical pathology & chemistry.
- Histopathology: no drug-induced adverse effects, including special stains
- Dose dependent PK, both plasma & CSF, cleared by 24 h.
- Cortisol suppression is persistent as expected, >24h
- NOAEL: single dose = 10 mg/dog; repeat dose = 2 mg/dog
- Dose of 10 mg Dexamethasone in 2 mL volume is chosen for clinical studies based on published use in clinical practice and supported by toxicology studies, endorsed by FDA during pre-IND meeting.
Hydrodynamic Study - SP-PC002
We conducted a hydrodynamic study of SP-102 (SEMDEXA™) in non-rodent animal species, which showed that epidural administration of SP-102 (SEMDEXA™) demonstrated an increased local residence half-life and a decreased flow from the injection site.
Intravascular Injection Study - SEM-005
We conducted a study to evaluate the accidental intravascular injection of SP-102 (SEMDEXA™) into the vertebral artery of non-rodent animals. There were no adverse clinical signs associated with the accidental intra-arterial injection of SP-102 (SEMDEXA™) following a 24-hour survival period.
