Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Aslanis, Vassilios ; Slack, Robert J. ; MacKinnon, Alison C. ; McClinton, Catherine ; Tantawi, Susan ; Gravelle, Lise ; Nilsson, Ulf J. LU ; Leffler, Hakon LU ; Brooks, Ashley and Khindri, Sanjeev K. , et al. (2023) In Cancer Chemotherapy and Pharmacology 91(3). p.267-280
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... (More)

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).

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Administration, Oral, Area Under Curve, Dose-Response Relationship, Drug, Double-Blind Method, Galectin 3/antagonists & inhibitors, Healthy Volunteers
in
Cancer Chemotherapy and Pharmacology
volume
91
issue
3
pages
14 pages
publisher
Springer
external identifiers
  • pmid:36914828
  • scopus:85149837304
ISSN
0344-5704
DOI
10.1007/s00280-023-04513-y
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
03106509-b24c-484c-851d-6bd91d223f08
date added to LUP
2023-05-01 22:24:43
date last changed
2024-06-16 05:01:01
@article{03106509-b24c-484c-851d-6bd91d223f08,
  abstract     = {{<p>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.</p><p>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.</p><p>RESULTS: All 78 participants received at least one GB1211 dose (<i>n</i> = 58) or placebo (<i>n</i> = 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.</p><p>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.</p><p>CLINICAL TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (identifier: NCT03809052).</p>}},
  author       = {{Aslanis, Vassilios and Slack, Robert J. and MacKinnon, Alison C. and McClinton, Catherine and Tantawi, Susan and Gravelle, Lise and Nilsson, Ulf J. and Leffler, Hakon and Brooks, Ashley and Khindri, Sanjeev K. and Marshall, Richard P. and Pedersen, Anders and Schambye, Hans and Zetterberg, Fredrik}},
  issn         = {{0344-5704}},
  keywords     = {{Humans; Administration, Oral; Area Under Curve; Dose-Response Relationship, Drug; Double-Blind Method; Galectin 3/antagonists & inhibitors; Healthy Volunteers}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{267--280}},
  publisher    = {{Springer}},
  series       = {{Cancer Chemotherapy and Pharmacology}},
  title        = {{Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor : a single- and multiple-dose first-in-human study in healthy participants}},
  url          = {{http://dx.doi.org/10.1007/s00280-023-04513-y}},
  doi          = {{10.1007/s00280-023-04513-y}},
  volume       = {{91}},
  year         = {{2023}},
}