Glen Clack, Christopher Moore, Linette Ruston, David Wilson, Annelize Koch, Danielle Webb, Nicholas Mallard
{"title":"一项 1 期随机、安慰剂对照研究，评估肠溶稳定型红景天 (SFX-01) 在男性参与者中的安全性、耐受性和药代动力学。","authors":"Glen Clack, Christopher Moore, Linette Ruston, David Wilson, Annelize Koch, Danielle Webb, Nicholas Mallard","doi":"10.1007/s12325-024-03018-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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<sup>®</sup>) is a patented synthetic form of d,l-SFN stabilized within a biologically inert alpha-cyclodextrin complex.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>max</sub>) 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<sub>max</sub> 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2022-001601-43; ISRCTN Study Registration number: ISRCTN9628565.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Phase 1 Randomized, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Enteric-Coated Stabilized Sulforaphane (SFX-01) in Male Participants.\",\"authors\":\"Glen Clack, Christopher Moore, Linette Ruston, David Wilson, Annelize Koch, Danielle Webb, Nicholas Mallard\",\"doi\":\"10.1007/s12325-024-03018-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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<sup>®</sup>) is a patented synthetic form of d,l-SFN stabilized within a biologically inert alpha-cyclodextrin complex.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>max</sub>) 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<sub>max</sub> 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2022-001601-43; ISRCTN Study Registration number: ISRCTN9628565.</p>\",\"PeriodicalId\":7482,\"journal\":{\"name\":\"Advances in Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-11-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12325-024-03018-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12325-024-03018-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
A Phase 1 Randomized, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Enteric-Coated Stabilized Sulforaphane (SFX-01) in Male Participants.
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 (Cmax) 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. 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.
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.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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