A Randomized, Placebo Controlled, Double-blind, Double-dummy, Three-way Crossover Trial to Investigate the Effect of Two Doses of BI 474121 on Ketamine Induced Cognitive Deficits in Healthy Male Subjects

To investigate the effect of BI 474121 compared to placebo on ketamine-induced cognitive deficits to predict efficacy in patients with cognitive disorders.

Start Date07 Nov 2022

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT04964453 / CompletedPhase 1

Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 474121 in Healthy Japanese Male Subjects (Doubleblind, Randomised, Placebo-controlled, Parallel Group Design)

Safety, tolerability, and pharmacokinetics of BI 474121 will be assessed in healthy Japanese male using single rising oral doses in order to provide the basis for an ongoing clinical development of BI 474121 for the treatment of cognitive impairment in patients with Alzheimer's Disease and schizophrenia.

Start Date21 Jul 2021

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT04716894 / CompletedPhase 1

Effect of Itraconazole on the Pharmacokinetics of a Single Oral Dose of BI 474121 in Healthy Male Subjects (an Open-label, Two-period Fixed Sequence Design Study)

The main objective of this trial is to investigate the effect on the exposure of BI 474121 in plasma when given as oral single dose together with multiple oral doses of itraconazole (Test, T) as compared to when given alone as oral single dose (Reference, R).

Start Date01 Feb 2021

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with BI-474121

100 Translational Medicine associated with BI-474121

100 Patents (Medical) associated with BI-474121

Literatures (Medical) associated with BI-474121

01 Sep 2024·Journal of Psychopharmacology

Safety, tolerability and pharmacokinetics of the phosphodiesterase 2 inhibitor BI 474121: An overview of phase I randomized trials in healthy volunteers

Article

Author: Goeldner, Rainer-Georg ; Yamamura, Norio ; Schaible, Jennifer ; Scholz, Andreas

Background: Cognitive impairment associated with schizophrenia predicts poor functional outcomes, but currently no efficacious pharmacotherapies are available. Aims: Four phase I trials examined the safety, tolerability and pharmacokinetics of the phosphodiesterase 2 inhibitor BI 474121, along with potential drug–drug interactions. Methods: Trial 1 evaluated single rising doses (SRDs) of BI 474121 versus placebo in healthy males. The influence of drug formulation and food on drug bioavailability was also examined. Trial 2 evaluated SRD of BI 474121 versus placebo in healthy Japanese males. Trial 3 evaluated multiple rising doses of BI 474121 in healthy young (with/without midazolam) and elderly (without midazolam) participants versus placebo. Trial 4 investigated interactions between itraconazole and single-dose BI 474121 in healthy males. Results/Outcomes: No deaths, serious adverse events (AEs), severe AEs or protocol-specified AEs of special interest were observed. BI 474121 absorbed rapidly during fasting, achieved maximum concentration of analyte in plasma and dose proportionality via tablet formulation, and decreased in a multiphasic manner. BI 474121 steady state occurred within 11 days of multiple oral administration. Multiple doses increased BI 474121 plasma concentrations, but did not alter the time course of plasma concentrations. Urinary excretion of unchanged BI 474121 was negligible. No clinically relevant inhibition or induction of CYP3A4 by BI 474121 was observed. Itraconazole co-administration produced higher exposures of BI 474121 versus BI 474121 alone. Conclusions/Interpretation: BI 474121 demonstrated favourable safety and pharmacokinetic profiles in healthy Caucasian and Japanese individuals, supporting further clinical development.

British Journal of Clinical Pharmacology

Effects of the phosphodiesterase 2 inhibitor BI 474121 on central nervous system cyclic guanosine monophosphate concentrations: Translational studies

Article

Author: Rosenbrock, Holger ; Zambori, Janos ; Schaible, Jennifer ; Goeldner, Rainer‐Georg ; van Kraaij, Sebastiaan ; Groeneveld, Geert Jan ; Kremer, Philip ; Schultheis, Christian

AbstractAimsPhosphodiesterase 2 (PDE2) regulates intracellular cyclic adenosine monophosphate and guanosine monophosphate (cAMP/cGMP) levels, which contribute to processes crucial for learning and memory. BI 474121, a potent and selective PDE2 inhibitor, is in development for treating cognitive impairment associated with schizophrenia.MethodsThe effects of BI 474121 on cGMP concentrations were first assessed in rat cerebrospinal fluid (CSF) to demonstrate central nervous system (CNS) and functional target engagement. Next, a Phase I study in healthy participants assessed the pharmacokinetics of BI 474121 in CSF vs. plasma, the pharmacodynamics of BI 474121 by measuring cGMP concentrations in the CSF, and the safety of BI 474121.ResultsIn rats, BI 474121 was associated with a dose‐dependent increase (71% at the highest dose tested [3.0 mg kg−1]) in cGMP levels in the CSF relative to vehicle (P < 0.001). In healthy participants, the maximum‐measured concentration CSF‐to‐plasma ratio for BI 474121 exposure was similar following single oral doses of BI 474121 2.5, 10, 20 and 40 mg (dose‐adjusted geometric mean: 8.96% overall). BI 474121 2.5–40 mg administration in healthy participants also increased cGMP levels in CSF (maximum exposure‐related change from baseline ratio, BI 474121: 1.44–2.20 vs. placebo: 1.26). The most common treatment‐emergent adverse event (AE) was mild‐to‐moderate post‐lumbar puncture syndrome, which resolved with standard treatment. No AEs of special interest were observed.ConclusionsBI 474121 crosses the blood–brain barrier to inhibit PDE2, supporting cGMP as a translational marker to monitor CNS target engagement. These findings promote further clinical development of BI 474121.ClinicalTrials.gov number (NCT04672954).

100 Deals associated with BI-474121

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 2	PL	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	DE	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	HU	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	SK	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	US	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	ES	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	FR	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	AU	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	JP	Boehringer Ingelheim GmbH	20 Nov 2020
Depressive Disorder, Major	Phase 2	RU	Boehringer Ingelheim GmbH	20 Nov 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04672954 (Pubmed)	Phase 1	cGMP	-	BI 474121 2.5 mg	cnntnbrbku(irqwnvtudz) = No AEs of special interest were observed ouikuljaya (iyexiycgrn ) View more	Positive	16 Jun 2024
				BI 474121 10 mg
NCT04672954 (CTgov)	Phase 1	-	24	Placebo (Placebo)	reujkqxmwa(arrirzeqbg) = zhfujljbck mkudsnhbes (ivqvnthnut, skeshbcihj - ghigufldtc) View more	-	08 Mar 2024
				2.5 milligram (mg) BI 474121 (2.5 Milligram (mg) BI 474121)	reujkqxmwa(arrirzeqbg) = dzcvznwyxq mkudsnhbes (ivqvnthnut, unrmwiehov - ghwqxauxrs) View more
NCT04964453 (CTgov)	Phase 1	Alzheimer Disease \| Cognitive Dysfunction \| Schizophrenia	32	Placebo (Placebo)	toywmhfzyh(shvylbxhbe) = qvxmxjzlmy ehplmgnsxo (zwjosphrzg, byrtydsgek - lfirzjuqhn) View more	-	07 Mar 2024
				BI 474121 (2.5 mg BI 474121)	toywmhfzyh(shvylbxhbe) = ecscjlbute ehplmgnsxo (zwjosphrzg, vxinpoolxc - xoqumupwol) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

BI-474121

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation