A Bioequivalence Study of Two Formulations of Oral Semaglutide in Healthy Participants.

IF 3.8 3区医学 Q2 Medicine

Diabetes Therapy Pub Date : 2025-02-01 Epub Date: 2024-12-21 DOI:10.1007/s13300-024-01674-8

Mette Søndergaard Nielsen, Lise Brøndsted, Martin Kankam, Gaetano Morelli, David Nguyen, Trine Vang Skjøth, Usha Rani Patted, Marloes van Hout

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引用次数: 0

Abstract

Introduction: The glucagon-like peptide-1 (GLP-1) analogue semaglutide is approved as an oral formulation for the treatment of type 2 diabetes. This study aimed to confirm bioequivalence between a new, second-generation (2G) oral semaglutide formulation (1.5, 4 and 9 mg) and the initially approved first-generation (1G) formulation (3, 7 and 14 mg).

Methods: This was a randomised, multicentre, open-label, full replicate crossover study to confirm bioequivalence between 2G and 1G oral semaglutide formulations at steady-state (SS) in healthy participants (NCT05227196). Participants were recruited to three groups. In each group, participants were randomised to one of two alternating sequences comparing once-daily oral semaglutide treatment of 9 and 14 mg (group 1), 4 and 7 mg (group 2) or 1.5 and 3 mg (group 3) at SS. Treatment duration was 20 weeks, comprising four 5-week steady-state periods on alternating formulations. Repeated 24-h blood sampling at the end of each steady-state period supported pharmacokinetic analysis. Co-primary endpoints were area under the semaglutide plasma concentration-time curve during a dosing interval at SS (AUC_0-24h,SS) and maximum semaglutide plasma concentration at SS (C_{max, 0-24h,SS}). Bioequivalence for co-primary endpoints was assessed using European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA) and Japan Pharmaceuticals and Medical Devices Agency (PMDA) criteria. Safety was monitored.

Results: A total of 222, 201 and 123 participants were recruited into groups 1, 2 and 3, respectively. The prespecified EMA, FDA and PMDA bioequivalence criteria were met for 2G versus 1G oral semaglutide for all three dose levels (1.5 vs 3 mg, 4 vs 7 mg and 9 vs 14 mg). The safety profile of 2G oral semaglutide was consistent with 1G oral semaglutide.

Conclusions: The 2G oral semaglutide formulation was confirmed as bioequivalent to 1G oral semaglutide, with no new safety concerns identified.

Trial registration: ClinicalTrials.gov identifier, NCT05227196.

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两种口服西马鲁肽制剂在健康受试者中的生物等效性研究。

胰高血糖素样肽-1 （GLP-1）类似物semaglutide已被批准作为治疗2型糖尿病的口服制剂。本研究旨在确认新的第二代（2G）口服semaglutide制剂（1.5、4和9 mg）与最初批准的第一代（1G）制剂（3、7和14 mg）之间的生物等效性。方法：这是一项随机、多中心、开放标签、全重复的交叉研究，以确认2G和1G口服西马鲁肽制剂在健康参与者（NCT05227196）稳态（SS）下的生物等效性。参与者被分为三组。在每一组中，参与者被随机分配到两个交替序列中的一个，比较每日一次口服西马鲁肽治疗9和14mg（第1组），4和7mg（第2组）或1.5和3mg（第3组）。治疗持续时间为20周，包括4个5周的交替配方稳态期。在每个稳态期结束时重复24小时血样支持药代动力学分析。共同主要终点是在给药间隔时间内，SS （AUC0-24h，SS）和SS时的最大semaglutide血药浓度（Cmax, 0-24h，SS）下的面积。采用欧洲药品管理局（EMA）、美国食品和药物管理局（FDA）和日本药品和医疗器械管理局（PMDA）标准评估共同主要终点的生物等效性。安全受到监控。结果：共有222人、201人、123人被纳入1、2、3组。在所有三种剂量水平（1.5 vs 3mg， 4 vs 7mg和9 vs 14mg）下，2G与1G口服semaglutide均符合预先规定的EMA、FDA和PMDA生物等效性标准。2G口服西马鲁肽的安全性与1G口服西马鲁肽一致。结论：2G口服西马鲁肽制剂被证实与1G口服西马鲁肽具有生物等效性，没有发现新的安全性问题。试验注册：ClinicalTrials.gov识别码，NCT05227196。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes 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 areas of diabetes. 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. Diabetes 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.