Abstract
Purpose :
SBI-100 is a novel prodrug of tetrahydrocannainol (THC). This first-in-human Phase 1 study evaluated the safety, tolerability and pharmacokinetics of topical ocular SBI-100 in healthy volunteers (HV).
Methods :
This randomized, double-masked, placebo-controlled, single-center study enrolled 48 HV. In the single ascending dose (SAD) study (n=24), HV were randomly assigned to receive a single dose of SBI-100 Ophthalmic Emulsion (SBI-100 OE) (0.5%, 1.0% or 2.0%) or placebo. In the multiple ascending dose (MAD) study (n=24), HV received BID dosing of either 0.5%, 1.0%, 2.0% or placebo for 5 days. PK was assessed for SBI-100, THC and 11-OH-THC. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs), clinical laboratory tests, electrocardiograms, vital signs, and physical examinations throughout the study period.
Results :
36 HV received SBI-100 OE and 12 received placebo. All HV in SAD cohorts completed the study and 1 HV from each of the MAD treatment groups discontinued treatment due to a TEAE not related to SBI-100 OE. Overall, ocular assessments yielded minimal changes from baseline and there were few clinically significant findings. Conjunctival hyperemia was reported in 1 HV in the SAD SBI-100 OE group and in 2 HV in the MAD SBI-100 OE 2% group; only the 2 occurrences in the MAD SBI-100 OE 2% group were considered related. Following administration of SBI-100 OE, plasma concentrations of SBI-100 reached peak levels within an hour, which was observed in both SAD and MAD. SBI-100 had low accumulation, with a mean Cmax accumulation ratio ranging from 1.258 to 2.036. No difference in IOP was found between SBI-100 OE and placebo. However, in an ad-hoc sub-group analysis of HV with baseline IOP > 17 mmHg, an average IOP reduction of 24% from baseline was observed.
Conclusions :
SBI-100 OE was generally well tolerated. No apparent systemic side effects that could be attributed to systemic exposure to THC were observed. The most reported TEAE was instillation site pain, but this generally resolved within 15 minutes and was not associated with hyperaemia. SBI-100 OE is being developed for the treatment of primary open angle glaucoma and ocular hypertension.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.