Remibrutinib (LOU064): A selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase I trial

Autor: Arvind Kinhikar, Angela Sinn, Alessio Maiolica, Rainard Fuhr, Annamaria Jakab, Martin Kaul, Carole Schuhler, Magdalena Kistowska, Peter End, Maciej Cabanski, Bruno Cenni
Rok vydání: 2021
Předmět:
Adult
Male
030213 general clinical medicine
Adolescent
Administration
Oral
RM1-950
Pharmacology
Basophil
030226 pharmacology & pharmacy
Asymptomatic
Article
General Biochemistry
Genetics and Molecular Biology
Young Adult
Food-Drug Interactions
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Agammaglobulinaemia Tyrosine Kinase
medicine
Humans
Immunologic Factors
Bruton's tyrosine kinase
General Pharmacology
Toxicology and Pharmaceutics
Protein Kinase Inhibitors
Aged
Skin Tests
Volume of distribution
Cross-Over Studies
Dose-Response Relationship
Drug
biology
CD63
business.industry
Research
General Neuroscience
Articles
General Medicine
Middle Aged
Healthy Volunteers
medicine.anatomical_structure
Pharmacodynamics
Toxicity
biology.protein
Female
Therapeutics. Pharmacology
Public aspects of medicine
RA1-1270
medicine.symptom
business
Zdroj: Clinical and Translational Science
Clinical and Translational Science, Vol 14, Iss 5, Pp 1756-1768 (2021)
ISSN: 1752-8062
1752-8054
DOI: 10.1111/cts.13005
Popis: Safe and effective new oral therapies for autoimmune, allergic, and inflammatory conditions remain a significant therapeutic need. Here, we investigate the human pharmacokinetics, pharmacodynamics (PDs), and safety of the selective, covalent Bruton’s tyrosine kinase (BTK) inhibitor, remibrutinib. Study objectives were explored in randomized single and multiple ascending dose (SAD and MAD, respectively) cohorts with daily doses up to 600 mg, and a crossover food effect (FE) cohort, in adult healthy subjects without (SAD [n =80]/FE [n =12]) or with asymptomatic atopic diathesis (MAD [n =64]). A single oral dose of remibrutinib (0.5‒600 mg) was rapidly absorbed (time to maximum concentration = 0.5 h‒1.25 h) with an apparent blood clearance of 280‒560 L/h and apparent volume of distribution of 400‒15,000 L. With multiple doses (q.d. and b.i.d.), no pronounced accumulation of remibrutinib was detected (mean residence time was
Databáze: OpenAIRE
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