A Phase 1 Randomized, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Enteric-Coated Stabilized Sulforaphane (SFX-01) in Male Participants.

Abstract

Sulforaphane (SFN) is a naturally occurring isothiocyanate associated with various health benefits, including reduced cancer risk, and has been extensively explored as a potential therapeutic. However, its inherent instability presents challenges in formulation, storage, and administration as a medicinal product. SFX-01 (Sulforadex®) is a patented synthetic form of d,l-SFN stabilized within a biologically inert alpha-cyclodextrin complex. The safety, tolerability, and pharmacokinetics of an enteric-coated tablet formulation of SFX-01 were evaluated in a randomized, double-blind, placebo-controlled, dose-escalation study [300mg once daily (46.2mg SFN), 300mg twice daily or 600mg once daily (92.4mg SFN)] over 7days in healthy male participants. Treatment-emergent adverse events (TEAEs) occurred in 94% of participants who received SFX-01 and were most commonly gastrointestinal events, which were mild in severity and related to treatment. Following ingestion of SFX-01 tablets, SFN was rapidly absorbed, with a timescale consistent with the enteric coating, and subsequently metabolized. The observed peak blood concentration (Cmax) for the sum of SFN and metabolites (total thiol) across all treatment cohorts ranged from 0.43 to 2.12µmol/L in 3-6h. Cmax data were considered inconclusive with respect to dose-proportionality and there was minimal evidence of accumulation of SFN and metabolites. Urinary excretion of SFN and individual metabolites ranged from<1 to 41%, and the proportion excreted did not appear to be influenced by the dose. This study demonstrated the safety and tolerability of SFX-01 over 7days and indicated that the pharmacokinetic behavior of SFX-01 enteric-coated tablets was in line with expectations. European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2022-001601-43; ISRCTN Study Registration number: ISRCTN9628565.