Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Mar;91(3):267-280.
doi: 10.1007/s00280-023-04513-y. Epub 2023 Mar 13.

Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor: a single- and multiple-dose first-in-human study in healthy participants

Vassilios Aslanis #  1 , Robert J Slack #  2 , Alison C MacKinnon  1 , Catherine McClinton  1 , Susan Tantawi  1 , Lise Gravelle  1 , Ulf J Nilsson  3 , Hakon Leffler  4 , Ashley Brooks  5 , Sanjeev K Khindri  1 , Richard P Marshall  1 , Anders Pedersen  1 , Hans Schambye  1 , Fredrik Zetterberg  1
Affiliations
Clinical Trial

Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor: a single- and multiple-dose first-in-human study in healthy participants

Vassilios Aslanis et al. Cancer Chemother Pharmacol. 2023 Mar.

Abstract

Purpose: Galectin-3, a β-galactoside-binding lectin, plays a key role in several cellular pathways involved in chronic inflammation, heart disease and cancer. GB1211 is an orally bioavailable galectin-3 inhibitor, developed to be systemically active. We report safety and pharmacokinetics (PK) of GB1211 in healthy participants.

Methods: This phase 1, double-blind, placebo-controlled, first-in-human study (NCT03809052) included a single ascending-dose phase (with a food-effect cohort) where participants across seven sequential cohorts were randomized 3:1 to receive oral GB1211 (5, 20, 50, 100, 200 or 400 mg) or placebo. In the multiple ascending-dose phase, participants received 50 or 100 mg GB1211 or placebo twice daily for 10 days. All doses were administered in the fasted state except in the food-effect cohort where doses were given 30 min after a high-fat meal.

Results: All 78 participants received at least one GB1211 dose (n = 58) or placebo (n = 20) and completed the study. No safety concerns were identified. Following single and multiple oral doses under fasted conditions, maximum GB1211 plasma concentrations were reached at 1.75-4 h (median) post-dose; mean half-life was 11-16 h. There was a ~ twofold GB1211 accumulation in plasma with multiple dosing, with steady-state reached within 3 days; 30% of the administered dose was excreted in urine as unchanged drug. Absorption in the fed state was delayed by 2 h but systemic exposure was unaffected.

Conclusion: GB1211 was well tolerated, rapidly absorbed, and displayed favorable PK, indicating a potential to treat multiple disease types. These findings support further clinical development of GB1211.

Clinical trial registration: The study was registered with ClinicalTrials.gov (identifier: NCT03809052).

Keywords: Clinical pharmacology–drug safety; Drug development–phase 1; Drug development–randomized controlled trial; Pharmacokinetics.

PubMed Disclaimer

Conflict of interest statement

CM, RJS, RPM, SKK, ST, VA: employees, personal fees–Galecto Biotech AB. ACM, AP, FZ, HS, LG: employees, personal fees, patents (CA2,794,066, US13/832,672, WO/2014/067986)–Galecto Biotech AB. UJN: shareholder, consultant–Galecto Biotech AB. HL: shareholder, consultant, grant recipient–Galecto Biotech AB. AB: company fees for conduct of the phase 1 clinical trial, patents–Galecto Biotech AB.

Figures

Fig. 1
Fig. 1
Mean plasma concentrations of GB1211 following A single oral fasted doses (5–400 mg) and B single oral doses (50 mg) in the fasted and fed state
Fig. 2
Fig. 2
Mean plasma concentrations of GB1211 following multiple oral doses – study day 10 BID twice daily
See this image and copyright information in PMC

References

    1. Li LC, Li J, Gao J. Functions of galectin-3 and its role in fibrotic diseases. J Pharmacol Exp Ther. 2014;351(2):336–343. doi: 10.1124/jpet.114.218370. - DOI - PubMed
    1. Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T. Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A. 2006;103(13):5060–5065. doi: 10.1073/pnas.0511167103. - DOI - PMC - PubMed
    1. Johannes L, Jacob R, Leffler H. Galectins at a glance. J Cell Sci. 2018;131(9):jcs208884. doi: 10.1242/jcs.208884. - DOI - PubMed
    1. Mori Y, Akita K, Yashiro M, Sawada T, Hirakawa K, Murata T, Nakada H. Binding of Galectin-3, a β-Galactoside-binding Lectin, to MUC1 protein enhances phosphorylation of extracellular signal-regulated Kinase 1/2 (ERK1/2) and Akt, promoting Tumor cell malignancy. J Biol Chem. 2015;290(43):26125–26140. doi: 10.1074/jbc.M115.651489. - DOI - PMC - PubMed
    1. Slack RJ, Mills R, Mackinnon AC. The therapeutic potential of galectin-3 inhibition in fibrotic disease. Int J Biochem Cell Biol. 2021;130:105881. doi: 10.1016/j.biocel.2020.105881. - DOI - PubMed

Publication types

Associated data

LinkOut - more resources