A Phase 1 Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, With an Open-Label Target Occupancy Study of BIIB113 in Healthy Participants

Parts A and B: The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending oral doses of BIIB113 in healthy participants. The secondary objectives of this study are to evaluate the single and multiple oral dose pharmacokinetic (PK) profile of BIIB113 in healthy participants and to evaluate the effect of food on the single oral dose of BIIB113 in healthy participants of Part A cohort 3.
Part C: The primary objectives of this study are to evaluate the safety and tolerability of single and multiple ascending oral doses of BIIB113 in healthy participants and to determine target occupancy (TO) as measured by O-GlcNAcase-Positron Emission Tomography (OGA-PET) of single and multiple oral doses of BIIB113 in healthy participants.

开始日期2022-01-24

申办/合作机构

Biogen, Inc.

100 项与碳[11C]BIO-1819578 相关的临床结果

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100 项与碳[11C]BIO-1819578 相关的转化医学

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100 项与碳[11C]BIO-1819578 相关的专利（医药）

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项与碳[11C]BIO-1819578 相关的文献（医药）

2023-07-19·ACS Chemical Neuroscience

Development of a Novel [¹¹C]CO-Labeled Positron Emission Tomography Radioligand [¹¹C]BIO-1819578 for the Detection of O-GlcNAcase Enzyme Activity

Article

作者: Martarello, Laurent ; Kaliszczak, Maciej ; Guckian, Kevin ; Genung, Nathan ; Hering, Heike ; Nag, Sangram ; Halldin, Christer ; Khani Maynaq, Yasir ; Lin, Edward ; Arakawa, Ryosuke ; Datta, Prodip ; Bolin, Martin ; Forsberg Morén, Anton

Imaging O-GlcNAcase OGA by positron emission tomography (PET) could provide information on the pathophysiological pathway of neurodegenerative diseases and important information on drug-target engagement and be helpful in dose selection of therapeutic drugs. Our aim was to develop an efficient synthetic method for labeling BIO-1819578 with carbon-11 using ¹¹CO for evaluation of its potential to measure levels of OGA enzyme in non-human primate (NHP) brain using PET. Radiolabeling was achieved in one-pot via a carbon-11 carbonylation reaction using [¹¹C]CO. The detailed regional brain distribution of [¹¹C]BIO-1819578 binding was evaluated using PET measurements in NHPs. Brain radioactivity was measured for 93 min using a high-resolution PET system, and radiometabolites were measured in monkey plasma using gradient radio HPLC. Radiolabeling of [¹¹C]BIO-1819578 was successfully accomplished, and the product was found to be stable at 1 h after formulation. [¹¹C]BIO-1819578 was characterized in the cynomolgus monkey brain where a high brain uptake was found (7 SUV at 4 min). A pronounced pretreatment effect was found, indicating specific binding to OGA enzyme. Radiolabeling of [¹¹C]BIO-1819578 with [¹¹C]CO was successfully accomplished. [¹¹C]BIO-1819578 binds specifically to OGA enzyme. The results suggest that [¹¹C]BIO-1819578 is a potential radioligand for imaging and for measuring target engagement of OGA in the human brain.

100 项与碳[11C]BIO-1819578 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床1期	英国	Biogen, Inc.	2022-01-24
阿尔茨海默症	临床1期	瑞典	Biogen, Inc.	2022-01-24
神经系统变性病	临床前	美国	Biogen MA, Inc.	2023-06-28