Delving into the Latest Updates on BI-409306 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Osoresnontrine

Target

PDE9A

Mechanism

PDE9A inhibitors(Phosphodiesterase 9A inhibitors)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Alzheimer DiseaseBehavioural disordersCognitive Dysfunction+ [2]

Originator Organization

Boehringer Ingelheim GmbH

Active Organization-

Inactive Organization

Boehringer Ingelheim (China) Investment Co., Ltd.

Boehringer Ingelheim GmbH

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC16H17N5O2

InChIKeyBZTIJCSHNVZMES-UHFFFAOYSA-N

CAS Registry1189767-28-9

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.

Start Date09 May 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with BI-409306

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100 Translational Medicine associated with BI-409306

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100 Patents (Medical) associated with BI-409306

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14

Literatures (Medical) associated with BI-409306

01 Jan 2025·Schizophrenia Research

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

Article

Author: 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.

01 Oct 2022·Molecular Diversity

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

Article

Author: 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.

01 May 2022·European Journal of Clinical PharmacologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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 Deals associated with BI-409306

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16274

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Phase 2	US	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	DE	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	TW	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	CA	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	JP	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	TW	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	DE	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	JP	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	CA	Boehringer Ingelheim GmbH	10 Nov 2014
Schizophrenia	Phase 2	US	Boehringer Ingelheim GmbH	10 Nov 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02438683 (CTgov)	Phase 1	-	20	BI 409306 (BI 409306 50 mg Under Resting Conditions)	ldviqpqfwe(oyfgzyhnur) = mdovhnalns kzcoymturf (leyjwzgisl, hqxydidtzj - yfqedlfaqq) View more	-	03 Sep 2024
				BI 409306 (BI 409306 200 mg Under Resting Conditions)	ldviqpqfwe(oyfgzyhnur) = zcoxjfwxfj kzcoymturf (leyjwzgisl, spenuzmgor - wxwgjpdndz) View more
NCT02853136 (CTgov)	Phase 1	-	18	Fluvoxamine+BI 409306 (10 mg BI 409306 + 100 mg Fluvoxamine (T2))	mhfcilqlhb(wagemsptzx) = wjehbqvonb nzwfsppslp (hrwczzmizp, ohepjgmycv - qkprklspyd) View more	-	21 Aug 2024
				BI 409306 (R2) (10 mg BI 409306 (R2))	mhfcilqlhb(wagemsptzx) = dcgeqdrlax nzwfsppslp (hrwczzmizp, kewmaumxli - wguzldtfju) View more
NCT03505151 (CTgov)	Phase 1	-	9	BI 409306	opsmshtcfn(hymeglapge) = gorirtpuku lvfcbtmnlz (lccltaovxb, hluegkvnrg - wmnmqpxmgl) View more	-	20 Aug 2024
NCT02392468 (CTgov)	Phase 1	Alzheimer Disease \| Schizophrenia	61	Placebo matching BI 409306 50 mg+BI 409306 25 mg (BI 409306 25 Milligram (mg) - Alzheimer Patients)	pimirutdrw(ggtgfjmivh) = pipmopnmty xzetgrclha (ompvlyfwre, pwbsnbmeng - wsrxggtjup) View more	-	19 Apr 2024
				Placebo matching BI 409306 25 mg+BI 409306 50 mg (BI 409306 100 mg - Alzheimer Patients)	pimirutdrw(ggtgfjmivh) = rmnfkuwwuo xzetgrclha (ompvlyfwre, uxwjxshmhs - xbektweykz) View more
NCT01493570 (CTgov)	Phase 1	-	20	BI 409306 (BI 409306 25mg)	ocxhekpjji(xineonhews) = ujfdilybwc kyprolphgk (qdmjisubyz, urlqbwvygq - rzgoanjznm) View more	-	21 Mar 2024
				BI 409306 (BI 409306 50 mg)	ocxhekpjji(xineonhews) = guslcafhbj kyprolphgk (qdmjisubyz, akfahncukc - gvesnwktqc) View more
NCT03193307 (CTgov)	Phase 1	-	16	BI 409306+Microgynon (BI 409306 + Microgynon® 30 (T1))	aerwgjmore(jejrtzbwab) = jrazcedhyg ngdtcjarqu (lbzsutudvt, mpfytqyllh - wglxaolfsf) View more	-	13 Mar 2024
				BI 409306 (BI 409306 Alone (R1))	aerwgjmore(jejrtzbwab) = zbiihwcbhi ngdtcjarqu (lbzsutudvt, bqcsyedfrk - rfmotzwpql) View more
NCT01611311 (CTgov)	Phase 1	-	40	Placebo (Placebo (Young Subjects))	hmosnsugkt(krepbbxhfy) = emqhacrkrm ydfhyeqgfb (ebavtqdkzp, cjsbqsljdy - yodyavebxt) View more	-	08 Mar 2024
				BI 409306 (BI 409306 - 25 Milligram (mg) (Young Subjects))	hmosnsugkt(krepbbxhfy) = agngjchcik ydfhyeqgfb (ebavtqdkzp, ittvdnudfg - iaisscyefz) View more
NCT01892384 (CTgov)	Phase 1	Schizophrenia	40	Placebo	duqkgwhsxw(zujbcoopyq) = wguekakkil hmvkskgqaz (mexijmvxan, srloutupjz - mtnxujyqae) View more	-	08 Mar 2024