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

Autor: Martin Kaul, Peter End, Maciej Cabanski, Carole Schuhler, Annamaria Jakab, Magdalena Kistowska, Arvind Kinhikar, Alessio Maiolica, Angela Sinn, Rainard Fuhr, Bruno Cenni
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Clinical and Translational Science, Vol 14, Iss 5, Pp 1756-1768 (2021)
Druh dokumentu: article
ISSN: 1752-8062
1752-8054
DOI: 10.1111/cts.13005
Popis: Abstract 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
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