ArticleClinical diabetes and endocrinology2021
Safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of BI 187004, an inhibitor of 11beta-hydroxysteroid dehydrogenase-1, in healthy male volunteers with overweight or obesity.
Article in Clinical diabetes and endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01587417 (A Randomised, Double-blind, Placebo-controlled Trial in Healthy Volunteers to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of 2.5 mg to 360 mg of BI 187004 CL), which is not on this map. Cited by 6 papers.
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A Randomised, Double-blind, Placebo-controlled Trial in Healthy Volunteers to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of 2.5 mg to 360 mg of BI 187004 CL
Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Safety, tolerability, pharmacodynamics and pharmacokinetics following once-daily doses of BI 187004, an inhibitor of 11 beta-hydroxysteroid dehydrogenase-1, over 28 days in patients with type 2 diabetes mellitus and overweight or obesity.Diabetes, obesity & metabolism · 2023Trial
- Selective Inhibition of 11beta-Hydroxysteroiddehydrogenase-1 with BI 187004 in Patients with Type 2 Diabetes and Overweight or Obesity: Safety, Pharmacokinetics, and Pharmacodynamics After Multiple Dosing Over 14 Days.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association · 2022Trial
- Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth.The Journal of clinical investigation · 2023Article
- Discovery of novel inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 usingJournal of diabetes and metabolic disorders · 2023Article
- 11β-HSD as a New Target in Pharmacotherapy of Metabolic Diseases.International journal of molecular sciences · 2022Review
- Novel Drugs for Diabetes Therapy.Handbook of experimental pharmacology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe study characterizes safety, tolerability, pharmacokinetic and pharmacodynamic profiles of single rising doses of the 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) inhibitor BI 187004 in healthy men with overweight or obesity.
methodsThis was a randomized, double-blind, parallel group, placebo-controlled study with administration of 2.5-360 mg BI 187004 or placebo once daily as single dose in 72 healthy male volunteers with overweight or obesity. Assessments included 11beta-HSD1 inhibition in the liver (assessed indirectly by urinary tetrahydrocortisol/tetrahydrocortisone ratio) and in subcutaneous adipose tissue ex vivo and determination of hypothalamus-pituitary-adrenal axis hormones.
resultsBI 187004 was well tolerated and safe in all tested dose groups. The incidence of drug-related adverse events was 16.7% (n = 9) for all 9 BI 187004 dose groups and 5.9% (n = 1) for placebo. All treatment groups were similar concerning kind and intensity of adverse events. No clinically relevant deviations in clinical laboratory or ECG parameters were reported. Exposure of BI 187004 increased non-proportionally over the entire dose range tested. The geometric mean apparent terminal half-life decreased from 33.5 h (5 mg) to 14.5 h (160 mg) remaining stable up to 360 mg. Renal excretion of BI 187004 was low (3-5%). Urinary tetrahydrocortisol/tetrahydrocortisone ratio decreased, indicating liver 11beta-HSD1 inhibition. Median inhibition of 11beta-HSD1 in subcutaneous adipose tissue biopsies following single dosing ranged from 86.8% (10 mg) to 99.5% (360 mg) after 10 h and from 59.4% (10 mg) to 98.6% (360 mg) after 24 h.
conclusionsBI 187004 as single dose was safe and well tolerated and is suitable for once daily dosing. There was significant, sustained 11beta-HSD1 inhibition in liver and adipose tissue.
trial registrationClinicalTrials.gov, NCT01587417 , registered on 26-Apr-2012.
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