Relative bioavailability and food effect of the galectin-3 inhibitor selvigaltin (GB1211) administered as a tablet in healthy participants (GALBA-1).

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-11-01 Epub Date: 2024-08-21 DOI:10.1007/s00280-024-04710-3
Vassilios Aslanis, Khalid Abd-Elaziz, Robert J Slack, Anne Brinch, Lise Gravelle, Wayne Morley, De Phung, Kimberly Herman, Ian Holyer, Karen Killerup Poulsen, Peter Dogterom, Susan Tantawi, Fredrik R Zetterberg, Brian Jacoby, Hans Schambye, Bertil Lindmark
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Abstract

Purpose: Overexpression of galectin-3, a β-galactoside-binding lectin, is associated with fibrotic diseases and cancer. Selvigaltin is an oral galectin-3 inhibitor, previously administered as a 50 mg capsule. This study aimed to evaluate the relative bioavailability and food effect of selvigaltin as a 100 mg tablet in healthy volunteers.

Methods: In this single-dose, randomized, three-period, crossover study (GALBA-1; NCT05747573), participants received selvigaltin as a 100 mg tablet (under fasted and fed conditions) or as two 50 mg capsules (under fasted conditions). Primary endpoints included plasma and urine pharmacokinetic (PK) parameters. Secondary endpoints were safety and tolerability.

Results: Of the 13 enrolled participants, 12 completed the study. Under fasted conditions, geometric mean maximum observed plasma concentration (Cmax) and systemic exposure (AUC0─inf) of selvigaltin were 161.0% and 84.0% higher, respectively, after administration of a tablet vs. capsules. Under fed vs. fasted conditions, geometric mean Cmax of the selvigaltin tablet was 20.0% lower, whereas AUC0─inf was unaffected. Geometric mean percentage of total dose of selvigaltin excreted in urine over 0─96 h was 30.3% and 35.9% for the tablet under fasted and fed conditions, respectively, and 14.5% for the capsules. No treatment-emergent severe or serious adverse events or study discontinuations due to a treatment-emergent adverse event were reported.

Conclusion: The tablet formulation of selvigaltin displayed higher bioavailability vs. the capsule formulation, with minimal effect of food on PK. Selvigaltin was well-tolerated during all treatments. These findings warrant further clinical development of the tablet formulation of selvigaltin without specific food restrictions.

Clinical trial registration: NCT05747573; February 28, 2023.

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以片剂形式给健康参与者服用的galectin-3抑制剂selvigaltin(GB1211)的相对生物利用度和食物效应(GALBA-1)。
目的:galectin-3 是一种 β-半乳糖苷结合凝集素,它的过度表达与纤维化疾病和癌症有关。Selvigaltin是一种口服galectin-3抑制剂,以前以50毫克胶囊的形式给药。本研究旨在评估健康志愿者服用 100 毫克片剂塞尔维加尔汀的相对生物利用度和食物效应:在这项单剂量、随机、三期交叉研究(GALBA-1;NCT05747573)中,参与者服用的是 100 毫克片剂(空腹和进食条件下)或两粒 50 毫克胶囊(空腹条件下)。主要终点包括血浆和尿液药代动力学(PK)参数。次要终点为安全性和耐受性:结果:13 名参加者中,12 人完成了研究。在空腹条件下,服用片剂与胶囊相比,舍维加尔汀的几何平均最大观察血浆浓度(Cmax)和全身暴露量(AUC0─inf)分别高出161.0%和84.0%。在进食与禁食条件下,舍维加尔汀片剂的几何平均Cmax降低了20.0%,而AUC0─inf则不受影响。在空腹和进食条件下,片剂在0-96小时内从尿液中排出的舍维加尔汀占总剂量的几何平均百分比分别为30.3%和35.9%,胶囊则为14.5%。未报告因治疗引起的严重不良事件或研究中止:结论:与胶囊剂相比,片剂的生物利用度更高,食物对PK的影响最小。在所有治疗过程中,塞尔维加尔汀的耐受性都很好。这些研究结果证明,在没有特定食物限制的情况下,可以进一步临床开发舍维加尔汀片剂:临床试验注册:NCT05747573;2023年2月28日。
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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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