The society and the use of laboratory animals: Scientific and ethical views

In this presentation we shall deal with the ways in which society obtains insight in the use of animals in experimental work, whether research or control. The individual elements in this are shown in Table 1. The arrows indicate the flow of material whether on paper, verbal or in other forms without indicating the strength. The upkeep of the standards in animal work is depending upon the correct use of the information collected in the laboratory animal science and the flow of information to the widely distributed users of animals. Society must control this and support progress. The use of experimental animals should be restricted and any use deemed necessary must be carried out with the highest degree of care and respect for the animal’s integrity and without pain. The wish to get insight must never result in the hampering of progress. On the other hand present days society and present days science are so deeply involved in each other that we experience an ever growing wish from the society to get insight into the ethics and means of the sciences. The users of animals in research have nothing to hide. On the other hand the judgement of the reason for the experiments and the ways they are carried out requires the understanding of all the relevant data and the intricate knowledge ofthe animal science. Therefore the control wanted by society must be left to a control committee of experts headed by a publicly appointed >>lay<< person, e.g. a judge, as in Denmark

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

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)