Qinghua Wang MD, Qiaoli Cui MD, Yulong Xu MSc, Gerald J. Prud'homme MD, Yuanxun Yang MSc, Dalong Zhu MD, Yiming Li MD, Yehong Yang MD, Juan Li MD
{"title":"Efsubaglutide Alfa在健康受试者中的安全性、药代动力学和药效学：一项随机、剂量递增的1期研究","authors":"Qinghua Wang MD, Qiaoli Cui MD, Yulong Xu MSc, Gerald J. Prud'homme MD, Yuanxun Yang MSc, Dalong Zhu MD, Yiming Li MD, Yehong Yang MD, Juan Li MD","doi":"10.1111/dom.16452","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>This Phase 1 study aimed to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose subcutaneous Efsubaglutide Alfa, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>This randomised, double-blind, placebo-controlled, single-dose escalation study was conducted at a single centre. A total of 48 healthy adults were randomised (6:2) across six dose cohorts (0.375, 0.75, 1.5, 3, 6 and 9 mg) to receive Efsubaglutide Alfa or placebo. Safety, PK and PD parameters were assessed.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Efsubaglutide Alfa exhibited dose-proportional PK, with a median <i>T</i><sub>max</sub> of 47.5–71.7 h and a mean half-life (<i>T</i><sub>1/2</sub>) of 121.4 h. Exposure increased linearly across doses (<i>C</i><sub>max</sub>: 37.1–832.4 ng/mL, AUC<sub>0–∞</sub>: 8699.6–193446.6 ng/mL·h). No serious AEs occurred; mild-to-moderate gastrointestinal AEs (nausea, vomiting, decreased appetite) were the most common in Efsubaglutide Alfa-treated subjects. Post-dose, fasting plasma glucose transiently declined on Day 1, returned to baseline by Day 2, and remained within −0.8 to +1.9 mmol/L relative to baseline (within expected physiological variability) through Day 28. Fasting insulin and C-peptide levels slightly increased on Day 1, normalised by Day 2, and remained stable. At Day 2, OGTT revealed reduced glucose excursions in Efsubaglutide Alfa recipients (<i>p</i> = 0.0150 vs. placebo; AUC ~0.7 mmol/L·2 h lower), while insulin and C-peptide levels remained unchanged. Dose-dependent weight loss peaked at Day 4–7, with up to a 4.0% reduction (<i>p</i> < 0.0001) at the higher dose, followed by a gradual return towards baseline by Day 28.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Efsubaglutide Alfa was well tolerated in healthy participants, with a favourable PK and PD profiles that support further clinical development in type 2 diabetes and metabolic disorders.</p>\n </section>\n </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 8","pages":"4220-4228"},"PeriodicalIF":5.7000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety, pharmacokinetics and pharmacodynamics of Efsubaglutide Alfa in healthy participants: A randomised, dose-escalation phase 1 study\",\"authors\":\"Qinghua Wang MD, Qiaoli Cui MD, Yulong Xu MSc, Gerald J. Prud'homme MD, Yuanxun Yang MSc, Dalong Zhu MD, Yiming Li MD, Yehong Yang MD, Juan Li MD\",\"doi\":\"10.1111/dom.16452\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>This Phase 1 study aimed to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose subcutaneous Efsubaglutide Alfa, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>This randomised, double-blind, placebo-controlled, single-dose escalation study was conducted at a single centre. A total of 48 healthy adults were randomised (6:2) across six dose cohorts (0.375, 0.75, 1.5, 3, 6 and 9 mg) to receive Efsubaglutide Alfa or placebo. Safety, PK and PD parameters were assessed.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Efsubaglutide Alfa exhibited dose-proportional PK, with a median <i>T</i><sub>max</sub> of 47.5–71.7 h and a mean half-life (<i>T</i><sub>1/2</sub>) of 121.4 h. Exposure increased linearly across doses (<i>C</i><sub>max</sub>: 37.1–832.4 ng/mL, AUC<sub>0–∞</sub>: 8699.6–193446.6 ng/mL·h). No serious AEs occurred; mild-to-moderate gastrointestinal AEs (nausea, vomiting, decreased appetite) were the most common in Efsubaglutide Alfa-treated subjects. Post-dose, fasting plasma glucose transiently declined on Day 1, returned to baseline by Day 2, and remained within −0.8 to +1.9 mmol/L relative to baseline (within expected physiological variability) through Day 28. Fasting insulin and C-peptide levels slightly increased on Day 1, normalised by Day 2, and remained stable. At Day 2, OGTT revealed reduced glucose excursions in Efsubaglutide Alfa recipients (<i>p</i> = 0.0150 vs. placebo; AUC ~0.7 mmol/L·2 h lower), while insulin and C-peptide levels remained unchanged. 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Safety, pharmacokinetics and pharmacodynamics of Efsubaglutide Alfa in healthy participants: A randomised, dose-escalation phase 1 study
Aims
This Phase 1 study aimed to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose subcutaneous Efsubaglutide Alfa, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants.
Materials and Methods
This randomised, double-blind, placebo-controlled, single-dose escalation study was conducted at a single centre. A total of 48 healthy adults were randomised (6:2) across six dose cohorts (0.375, 0.75, 1.5, 3, 6 and 9 mg) to receive Efsubaglutide Alfa or placebo. Safety, PK and PD parameters were assessed.
Results
Efsubaglutide Alfa exhibited dose-proportional PK, with a median Tmax of 47.5–71.7 h and a mean half-life (T1/2) of 121.4 h. Exposure increased linearly across doses (Cmax: 37.1–832.4 ng/mL, AUC0–∞: 8699.6–193446.6 ng/mL·h). No serious AEs occurred; mild-to-moderate gastrointestinal AEs (nausea, vomiting, decreased appetite) were the most common in Efsubaglutide Alfa-treated subjects. Post-dose, fasting plasma glucose transiently declined on Day 1, returned to baseline by Day 2, and remained within −0.8 to +1.9 mmol/L relative to baseline (within expected physiological variability) through Day 28. Fasting insulin and C-peptide levels slightly increased on Day 1, normalised by Day 2, and remained stable. At Day 2, OGTT revealed reduced glucose excursions in Efsubaglutide Alfa recipients (p = 0.0150 vs. placebo; AUC ~0.7 mmol/L·2 h lower), while insulin and C-peptide levels remained unchanged. Dose-dependent weight loss peaked at Day 4–7, with up to a 4.0% reduction (p < 0.0001) at the higher dose, followed by a gradual return towards baseline by Day 28.
Conclusions
Efsubaglutide Alfa was well tolerated in healthy participants, with a favourable PK and PD profiles that support further clinical development in type 2 diabetes and metabolic disorders.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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