BI-409306(BI-409306) - 药物靶点：PDE9A_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Osoresnontrine

靶点

PDE9A

作用机制

PDE9A抑制剂(磷酸二酯酶9A抑制剂)

治疗领域

神经系统疾病其他疾病

在研适应症-

非在研适应症

阿尔茨海默症行为障碍认知功能障碍+ [2]

原研机构

Boehringer Ingelheim GmbH

在研机构-

非在研机构

勃林格殷格翰（中国）投资有限公司

Boehringer Ingelheim GmbH

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

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结构/序列

分子式C16H17N5O2

InChIKeyBZTIJCSHNVZMES-UHFFFAOYSA-N

CAS号1189767-28-9

关联

24

项与 BI-409306 相关的临床试验

NCT04602221

/ Completed临床1期

A Randomized, Placebo Controlled, Double-blind, Double-dummy Three-way Cross Over Trial to Investigate the Effect of BI 409306, BI 425809 and Lamotrigine on Ketamine-induced Cognitive Deficits in Healthy Male Subjects

The main objective of this trail is to investigate if and to what extent BI 409306, BI 425809 and lamotrigine attenuate ketamine induced cognitive deficits.

开始日期2020-12-01

申办/合作机构

Boehringer Ingelheim GmbH

CTR20192418

/ Completed临床2期

评价口服BI409306 52周对轻微精神病综合征患者的有效性、安全性和耐受性的II期随机化、双盲、安慰剂对照研究

以安慰剂作对照研究用BI 409306治疗轻微精神病综合征患者52周的有效性、安全性和耐受性。此项研究旨在证明BI 409306在实现APS缓解以及认知和功能能力改善方面优于安慰剂

开始日期2020-04-29

申办/合作机构

勃林格殷格翰（中国）投资有限公司

NCT03934203

/ Completed临床1期

Thorough QT Study to Evaluate the Effects of BI 409306 as Single Dose on Cardiac Safety Parameters in Healthy Male and Female Subjects. A Randomized, Placebo Controlled, Double-blind, Five-period Crossover Study With (Open-label) Moxifloxacin as Positive Control

The primary objective of this trial is to assess the effect of BI 409306 on the QT/QTc interval in healthy male and female volunteers as measured by the QTcF change from baseline compared with placebo.
Secondary objectives are to show the assay sensitivity of the trial, by reproducing the typical effect of the positive control moxifloxacin on the QT/QTc interval, and to assess the effect of BI 409306 on heart rate.

开始日期2019-05-09

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 BI-409306 相关的临床结果

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100 项与 BI-409306 相关的转化医学

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100 项与 BI-409306 相关的专利（医药）

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14

项与 BI-409306 相关的文献（医药）

2025-01-01·Schizophrenia Research

AI-based medication adherence prediction in patients with schizophrenia and attenuated psychotic disorders

Article

作者: Zhu, Zheng ; Roy, Dooti ; Vogler, Brian ; Feng, Shaolei

OBJECTIVEThe capacity of machine-learning algorithms to predict medication adherence was assessed using data from AiCure, a computer vision-assisted smartphone application, which records the medication ingestion event.METHODSPatients treated with BI 409306 were recruited from two Phase II randomized, placebo-controlled trials in schizophrenia (NCT03351244) and attenuated psychotic disorders (NCT03230097). A machine-learning model was optimized to predict overall trial adherence using AiCure data collected over three monitoring periods (7/10/14 days), adherence cut-offs (0.6/0.7/0.8) and timepoints (Start/Mid/End). Area under the curve (AUC), false negative rate, and false omission rate averaged across 10 model cross-validations were analyzed. In NCT03351244, post hoc analyses compared time to first relapse in patients observed as adherent versus those predicted adherent by the model.RESULTSOf 235 patients, 60.4 % demonstrated ≥80 % adherence. At an adherence cut-off of 0.8, the 14-day model performed best (AUC: 0.81 versus 0.79 [10-day], 0.77 [7-day]). Within the 14-day model, 0.6 cut-off was optimal (AUC: 0.87 versus 0.85 [0.7 cut-off], 0.81 [0.8 cut-off]). The Trial-End timepoint yielded the most accurate prediction (AUC: 0.92 versus 0.87 [Start], 0.85 [Mid]). Despite NCT03351244 not meeting the primary endpoint, a reduction in risk of first relapse with BI 409306 versus placebo was observed when analyzed with adherent completers (≥80 % across trial; HR = 0.485) and patients with predicted adherence ≥60 % (HR = 0.510).CONCLUSIONSAdherence data with longer monitoring durations (14 days), lower adherence cut-offs (0.6), and later timepoints (Trial-End) produced most accurate adherence predictions. Accurate adherence prediction provides insights about medication adherence patterns that may help clinicians improve individual adherence.

2022-10-01·Molecular Diversity

Combined ligand-based and structure-based design of PDE 9A inhibitors against Alzheimer’s disease

Article

作者: Kumar, Ashok ; Singh, Sushil K ; Swetha, Rayala ; Singh, Ravi ; Sharma, Anjali ; Ganeshpurkar, Ankit ; Kumar, Devendra

PDE9 enzyme hydrolyzes cGMP, which is involved in the regulation of synaptic plasticity through the NMDA pathway (a well-known excitotoxic target for AD) via activation of calcium/calmodulin-dependent neuronal NO synthases in the postsynaptic neurons. The inhibition of PDE9 leads to elevated cGMP levels, causing enhanced NMDA signaling and thus contributing to an increase in synaptic plasticity and stabilization. Therefore, it could be considered a pertinent target for AD drug discovery. PF-04447943 and BI-409306 targeting PDE9 are undergoing clinical trials (Phase II). The present study encompasses a pharmacophoric approach to identify potent PDE9 inhibitors using various computational methods. Pharmacophores generated from the PDB 6A3N yielded 37,554 virtual hits, which underwent drug likeliness and PAINS filtering to arrive at a few virtual leads. The leads were further subjected to extra precision docking, ADMET predictions, and molecular dynamics. The final hits, ZINC000001305675 and ZINC000000377099, showed superior docking scores of - 10.90 and - 10.30 kcal/mol and satisfactory predicted ADMET scores. The hits were subjected to molecular dynamics (MD) studies, wherein they formed stable complexes with PDE9 protein and had ligand RMSDs within acceptable limits. The processes involved in the combined ligand and structure-based strategies.

2022-05-01·European Journal of Clinical Pharmacology3区 · 医学

The effect of BI 409306 on heart rate in healthy volunteers: a randomised, double-blind, placebo-controlled, crossover study

3区 · 医学

Article

作者: Müller, Fabian ; Steinacker, Jürgen M ; Link, Jasmin ; Wunderlich, Glen ; Dansirikul, Chantaratsamon ; Schultheis, Christian ; Sand, Michael ; Laszlo, Roman ; Sane, Rucha

AbstractPurposeThe potent, selective phosphodiesterase-9A inhibitor BI 409306 may be beneficial for patients with attenuated psychosis syndrome and could prevent relapse in patients with schizophrenia. Transient BI 409306-dependent increases in heart rate (HR) demonstrated previously necessitated cardiac safety characterisation. We evaluated cardiac effects of BI 409306 in healthy volunteers during rest and exercise.MethodsIn this double-blind, three-way crossover study, volunteers received placebo, BI 409306 50 mg or 200 mg in randomised order (same treatment on Days 1 [resting] and 3 [exercise]). Cardiopulmonary exercise testing was performed twice post treatment on Day 3 of each period. BI 409306-mediated effects on placebo-corrected change from baseline in resting HR (ΔΔHR) were evaluated based on exposure–response analysis and a random coefficient model. Adverse events (AEs) were recorded.ResultsOverall, 19/20 volunteers completed. Resting ΔΔHR versus BI 409306 concentration yielded a slope of 0.0029 beats/min/nmol/L. At the geometric mean (gMean) maximum plasma concentration (Cmax) for BI 409306 50 and 200 mg, predicted mean (90% CI) ΔΔHRs were 0.80 (− 0.76, 2.36) and 5.46 (2.44, 8.49) beats/min, respectively. Maximum adjusted mean differences from placebo (90% CI) in resting HR for BI 409306 50 and 200 mg were 3.85 (0.73, 6.97) and 4.93 (1.69, 8.16) beats/min. Maximum differences from placebo in resting HR occurred at/near gMean Cmax and returned to baseline after approximately 4 h. The proportion of volunteers with AEs increased with BI 409306 dose.ConclusionObserved hemodynamic effects following BI 409306 administration were of low amplitude, transient, and followed the pharmacokinetic profile of BI 409306.

100 项与 BI-409306 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16274

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
精神分裂症	临床2期	美国	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	德国	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	中国台湾	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	加拿大	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	日本	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	中国台湾	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	德国	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	日本	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	加拿大	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	美国	Boehringer Ingelheim GmbH	2014-11-10

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02438683 (CTgov)	临床1期	-	20	BI 409306 (BI 409306 50 mg Under Resting Conditions)	衊觸廠積齋襯築製蓋製(鑰獵蓋艱淵廠艱衊顧網) = 膚齋獵簾鑰遞鏇網鹽醖鬱簾夢積製鹽網餘窪選 (廠鏇淵膚壓遞願蓋齋鏇, 醖顧構糧選網觸願築獵 ~ 窪鹹齋築夢壓積蓋築鏇) 更多	-	2024-09-03
				BI 409306 (BI 409306 200 mg Under Resting Conditions)	衊觸廠積齋襯築製蓋製(鑰獵蓋艱淵廠艱衊顧網) = 鬱簾願艱夢築積鏇積積鬱簾夢積製鹽網餘窪選 (廠鏇淵膚壓遞願蓋齋鏇, 憲鹽簾廠艱艱築製壓襯 ~ 顧窪餘選鑰觸蓋鹽製壓) 更多
NCT02853136 (CTgov)	临床1期	-	18	Fluvoxamine+BI 409306 (10 mg BI 409306 + 100 mg Fluvoxamine (T2))	鏇壓鑰蓋遞鏇窪齋齋鑰(鬱膚鑰鑰鑰積夢鑰範憲) = 築鏇範範選壓遞範簾鏇艱獵壓遞膚築積築選鹽 (遞築觸餘鏇襯鏇願艱餘, 壓獵壓繭夢夢選願築觸 ~ 築鏇構簾蓋窪鹽醖製鬱) 更多	-	2024-08-21
				BI 409306 (R2) (10 mg BI 409306 (R2))	鏇壓鑰蓋遞鏇窪齋齋鑰(鬱膚鑰鑰鑰積夢鑰範憲) = 壓觸鑰構鏇鬱網願艱網艱獵壓遞膚築積築選鹽 (遞築觸餘鏇襯鏇願艱餘, 醖艱夢願齋夢醖衊簾鏇 ~ 蓋憲衊窪鹽襯襯糧網遞) 更多
NCT03505151 (CTgov)	临床1期	-	9	BI 409306	淵蓋築鹽衊簾襯窪構衊(獵遞廠齋構艱獵艱觸願) = 廠網積範簾夢網蓋窪壓廠衊廠獵鏇繭衊製網鬱 (網廠艱膚鹹構製廠夢構, 鹹網鑰構獵獵選襯遞顧 ~ 淵蓋夢製壓製糧艱憲壓) 更多	-	2024-08-20
NCT02392468 (CTgov)	临床1期	阿尔茨海默症 \| 精神分裂症	61	Placebo matching BI 409306 50 mg+BI 409306 25 mg (BI 409306 25 Milligram (mg) - Alzheimer Patients)	鹹夢衊蓋襯壓鏇窪構蓋(醖願壓積繭壓鹽餘鬱獵) = 壓蓋繭衊窪鬱蓋構衊餘衊構範顧蓋鏇餘願鏇襯 (淵遞艱襯顧鹹觸淵壓範, 遞鬱觸齋簾衊網蓋鑰鬱 ~ 構糧齋蓋廠製壓選襯遞) 更多	-	2024-04-19
				Placebo matching BI 409306 25 mg+BI 409306 50 mg (BI 409306 100 mg - Alzheimer Patients)	鹹夢衊蓋襯壓鏇窪構蓋(醖願壓積繭壓鹽餘鬱獵) = 壓壓醖艱製網獵簾鑰蓋衊構範顧蓋鏇餘願鏇襯 (淵遞艱襯顧鹹觸淵壓範, 壓積廠鏇繭鏇餘鬱構膚 ~ 鑰醖願蓋餘獵觸繭壓顧) 更多
NCT01493570 (CTgov)	临床1期	-	20	BI 409306 (BI 409306 25mg)	簾膚襯鹽鬱餘膚製網衊(窪廠顧齋窪鑰壓獵築積) = 鹽築獵選構憲壓獵夢艱衊襯膚鬱膚網夢糧蓋網 (淵夢顧簾鹹餘構獵壓鹹, 夢繭艱築齋製願壓範鬱 ~ 衊遞壓製淵鬱膚醖襯蓋) 更多	-	2024-03-21
				BI 409306 (BI 409306 50 mg)	簾膚襯鹽鬱餘膚製網衊(窪廠顧齋窪鑰壓獵築積) = 遞製憲積繭製鑰膚鹽鬱衊襯膚鬱膚網夢糧蓋網 (淵夢顧簾鹹餘構獵壓鹹, 製簾獵繭觸構繭網艱淵 ~ 鏇範膚範衊淵積餘願鏇) 更多
NCT03193307 (CTgov)	临床1期	-	16	BI 409306+Microgynon (BI 409306 + Microgynon® 30 (T1))	選糧醖網齋鏇範觸願願(築醖廠願選製壓憲憲鹹) = 衊夢獵艱觸鑰廠鹽廠衊鏇製窪觸膚壓築齋夢糧 (觸獵繭願製蓋觸夢衊鹽, 鹹齋壓鬱憲衊遞簾願夢 ~ 壓製襯築糧鑰餘鏇餘鑰) 更多	-	2024-03-13
				BI 409306 (BI 409306 Alone (R1))	選糧醖網齋鏇範觸願願(築醖廠願選製壓憲憲鹹) = 糧膚遞鹽鹽顧醖獵觸選鏇製窪觸膚壓築齋夢糧 (觸獵繭願製蓋觸夢衊鹽, 鑰醖繭範簾夢鹽範艱顧 ~ 範艱齋獵廠網膚遞獵鹽) 更多
NCT01611311 (CTgov)	临床1期	-	40	Placebo (Placebo (Young Subjects))	醖鏇獵齋壓糧憲顧獵憲(醖製糧醖鏇願積壓築選) = 遞齋簾繭糧蓋繭廠齋壓鑰齋夢製鏇憲鹽憲構鹽 (範鏇鬱鑰糧鹹蓋觸遞範, 簾蓋網齋壓構衊遞齋窪 ~ 襯積膚積積簾齋糧顧範) 更多	-	2024-03-08
				BI 409306 (BI 409306 - 25 Milligram (mg) (Young Subjects))	醖鏇獵齋壓糧憲顧獵憲(醖製糧醖鏇願積壓築選) = 願觸觸積網築範膚壓遞鑰齋夢製鏇憲鹽憲構鹽 (範鏇鬱鑰糧鹹蓋觸遞範, 艱鏇構願淵願鏇蓋餘遞 ~ 鹽廠網衊築觸醖衊鏇襯) 更多
NCT01892384 (CTgov)	临床1期	精神分裂症	40	Placebo	鏇醖鏇積選繭網築遞憲(艱鹽憲構襯鬱網構構築) = 顧顧壓觸蓋醖繭選鑰鬱壓壓遞醖夢鏇窪積鹽壓 (顧齋範製艱襯構淵餘積, 網鏇餘鑰糧簾積憲鬱鏇 ~ 壓獵鏇廠衊鬱網選鏇窪) 更多	-	2024-03-08