Abstract：
OBJECTIVE: The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects.
METHODS: This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose.
RESULTS: Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders.
CONCLUSIONS: At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.
METHODS: This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose.
RESULTS: Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders.
CONCLUSIONS: At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.
摘要：
目的：本试验(NCT04016974)研究药物动力学,药效学,口服司马鲁肽的安全性和耐受性，首次口服胰高血糖素样肽-1类似物治疗2型糖尿病，在健康的中国科目中。
方法：这种单中心，多剂量,安慰剂对照试验将32名健康中国成年人随机分配至每日一次口服司美鲁肽(从3mg升至14mg)或安慰剂,共12周.在治疗和随访期间定期收集血样。主要终点是在稳态（AUC0-24h，sema,SS）。次要药代动力学终点包括稳态时观察到的最大塞马鲁肽血浆浓度（Cmax，sema,SS）。支持性次要药效学终点包括体重和空腹血糖的变化。
结果：所有口服司马鲁肽剂量治疗均显示，健康中国受试者在稳态时司马鲁肽暴露量呈剂量依赖性增加，通过AUC0-24h测定，sema,SS（对于3、7和14mg的口服司马鲁肽，为233、552和1288h·nmol/L，分别)和Cmax，sema,SS.与安慰剂相比，口服司马鲁肽治疗与治疗结束时体重（p=0.0001）和空腹血糖（p=0.0011）的显着降低相关。口服司马鲁肽的安全性和耐受性与胰高血糖素样肽-1受体激动剂的已知概况一致，没有严重或血糖确认的症状性低血糖事件，严重不良事件或死亡。最常见的不良事件是胃肠道疾病。
结论：在稳态下，在健康的中国受试者中，口服司马鲁肽暴露是剂量依赖性的，并且接近剂量比例。这与先前口服司马鲁肽的临床药理学结果一致。
方法：这种单中心，多剂量,安慰剂对照试验将32名健康中国成年人随机分配至每日一次口服司美鲁肽(从3mg升至14mg)或安慰剂,共12周.在治疗和随访期间定期收集血样。主要终点是在稳态（AUC0-24h，sema,SS）。次要药代动力学终点包括稳态时观察到的最大塞马鲁肽血浆浓度（Cmax，sema,SS）。支持性次要药效学终点包括体重和空腹血糖的变化。
结果：所有口服司马鲁肽剂量治疗均显示，健康中国受试者在稳态时司马鲁肽暴露量呈剂量依赖性增加，通过AUC0-24h测定，sema,SS（对于3、7和14mg的口服司马鲁肽，为233、552和1288h·nmol/L，分别)和Cmax，sema,SS.与安慰剂相比，口服司马鲁肽治疗与治疗结束时体重（p=0.0001）和空腹血糖（p=0.0011）的显着降低相关。口服司马鲁肽的安全性和耐受性与胰高血糖素样肽-1受体激动剂的已知概况一致，没有严重或血糖确认的症状性低血糖事件，严重不良事件或死亡。最常见的不良事件是胃肠道疾病。
结论：在稳态下，在健康的中国受试者中，口服司马鲁肽暴露是剂量依赖性的，并且接近剂量比例。这与先前口服司马鲁肽的临床药理学结果一致。
