Single‑Dose Pharmacokinetics and Safety of the Oral Galectin‑3 Inhibitor, Selvigaltin (GB1211), in Participants with Hepatic Impairment

  • Clin Drug Investig. 2024 Oct 2. doi: 10.1007/s40261-024-01395-7.
Vassilios Aslanis  1 ,  Michael Gray  2 ,  Robert J Slack  2 ,  Fredrik R Zetterberg  2 ,  Dimitar Tonev  2 ,  De Phung  2 ,  Becky Smith  2 ,  Brian Jacoby  2 ,  Hans Schambye  2 ,  Zahari Krastev  3 ,  Anna-Lena Ungell  4 ,  Bertil Lindmark  2
Affiliations
  • 1. Galecto Biotech AB, Ole Maaloes Vej 3, 2200, Copenhagen, Denmark. [email protected].
  • 2. Galecto Biotech AB, Ole Maaloes Vej 3, 2200, Copenhagen, Denmark.
  • 3. MC Comac Medical Ltd, Sofia, Bulgaria.
  • 4. Ungell ADME Consulting AB, Näsbovägen, Västra Frölunda, Sweden.
PMID: 39358661 DOI: 10.1007/s40261-024-01395-7
Abstract

Background and objectives: Selvigaltin (GB1211), an orally available small molecule Galectin-3 Inhibitor developed as a treatment for liver fibrosis and cirrhosis, was evaluated to assess the effect of hepatic impairment on its pharmacokinetics and safety to address regulatory requirements.

Methods: GULLIVER-2 was a Phase Ib/IIa three-part study. Parts 1 and 3 had single-dose, open-label designs assessing pharmacokinetics (plasma [total and unbound] and urine), safety, and tolerability of 100 mg oral selvigaltin in participants with moderate (Child-Pugh B, Part 1) or severe (Child-Pugh C, Part 3) hepatic impairment, compared with healthy-matched participants (n = 6 each).

Results: All participants received selvigaltin and completed the study. No adverse events were reported. The median time to reach maximum total plasma concentration following drug administration was of 3.49 and 4.00 h post-dose for Child-Pugh B and C participants, respectively; comparable with controls. Total plasma exposure was higher for participants with hepatic impairment compared with controls. Whilst maximum plasma concentration (Cmax) was unaffected in Child-Pugh B participants, area under the plasma concentration-time curve from time zero to infinity (AUC∞) increased by ~ 1.7-fold compared with controls, and half-life was prolonged (geometric mean 28.15 vs 16.38 h). In Child-Pugh C participants, Cmax increased by ~ 1.3-fold, AUC∞ increased by ~ 1.5-fold, and half-life was prolonged (21.05 vs 16.14 h). No trend was observed in plasma unbound fractions or urinary excretion of unchanged selvigaltin in either group.

Conclusion: Hepatic impairment increased selvigaltin exposure without safety concerns. These data can inform dose recommendations for future clinical programmes.

Trial registration: Clinicaltrials.gov NCT05009680.

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