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

Abstract

Introduction: 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.

Methods: 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 [300 mg once daily (46.2 mg SFN), 300 mg twice daily or 600 mg once daily (92.4 mg SFN)] over 7 days in healthy male participants.

Results: 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 (C_max) for the sum of SFN and metabolites (total thiol) across all treatment cohorts ranged from 0.43 to 2.12 µmol/L in 3-6 h. C_max 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.

Conclusion: This study demonstrated the safety and tolerability of SFX-01 over 7 days and indicated that the pharmacokinetic behavior of SFX-01 enteric-coated tablets was in line with expectations.

Trial registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2022-001601-43; ISRCTN Study Registration number: ISRCTN9628565.