DNL 104, a Centrally Penetrant RIPK 1 Inhibitor, Inhibits RIP 1 Kinase Phosphorylation in a Randomized Phase I Ascending Dose Study in Healthy Volunteers

2019 ◽  
Vol 107 (2) ◽  
pp. 406-414 ◽  
Author(s):  
Hendrika W. Grievink ◽  
Jules A.A.C. Heuberger ◽  
Fen Huang ◽  
Rinkal Chaudhary ◽  
Willem A.J. Birkhoff ◽  
...  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhong-ping Gou ◽  
Wei Zhang ◽  
Xiu-fang Liang ◽  
Ying Wang ◽  
Ju-hong Mou ◽  
...  

Abstract Background This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins. Methods A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1–8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9–11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events. Results No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools. Conclusions DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e14504-e14504
Author(s):  
Jacqueline M Liu ◽  
Xinghe Wang ◽  
Jin Wang ◽  
Lu Qi ◽  
Zejuan Wang ◽  
...  

2019 ◽  
Vol 39 (9) ◽  
pp. 873-887 ◽  
Author(s):  
Michael E. Rothenberg ◽  
Michael Tagen ◽  
Jae H. Chang ◽  
Janel Boyce-Rustay ◽  
Michel Friesenhahn ◽  
...  

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