Delving into the Latest Updates on JNJ-42165279 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

FAAH

Mechanism

FAAH inhibitors(Anandamide amidohydrolase inhibitors)

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication

Autism Spectrum DisorderNeuralgia

Inactive Indication

Anxiety DisordersDepressive Disorder, MajorPhobia, Social+ [1]

Originator Organization

Janssen Global Services LLC

Active Organization

Johnson & JohnsonJanssen Research & Development LLC

Inactive Organization

Janssen Pharmaceutica NVJanssen-Cilag International NV

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC18H17ClF2N4O3

InChIKeyYWGYNGCRVZLMCS-UHFFFAOYSA-N

CAS Registry1346528-50-4

The purpose of this study is to evaluate the efficacy and safety and tolerability of JNJ-42165279 in participants with major depressive disorder (MDD) with anxiety symptoms who have had inadequate response to treatment with a selective serotonin reuptake inhibitor (SSRI) or serotonergic/noradrenergic reuptake inhibitor (SNRI).

Start Date07 Oct 2015

Sponsor / Collaborator

Janssen Research & Development LLC

100 Clinical Results associated with JNJ-42165279

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100 Translational Medicine associated with JNJ-42165279

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100 Patents (Medical) associated with JNJ-42165279

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7

Literatures (Medical) associated with JNJ-42165279

01 Aug 2021·Toxicologic PathologyQ4 · MEDICINE

Exacerbation of Background Nuclear Cataracts in Sprague-Dawley Rats in Embryo-Fetal Development Studies With JNJ-42165279, a Fatty Acid Amide Hydrolase Inhibitor

Q4 · MEDICINE

Article

Author: Roosen, Wendy ; Bailey, Graham ; Lachau-Durand, Sophie ; van Heerden, Marjolein ; Ndifor, Anthony

Fetal examinations in embryo-fetal developmental (EFD) studies are based on macroscopic and dissecting microscopic evaluations, and histopathology is rarely performed other than to confirm macroscopic findings. Fetal lens examination is therefore generally limited to the presence, size, shape, and color of any abnormality. In a Sprague-Dawley rat EFD study with the fatty acid amide hydrolase (FAAH) inhibitor JNJ-42165279, an unusually high incidence of macroscopic granular foci was noted within the lens of gestation day 21 fetuses across all groups including controls, with higher incidence in the high-dose group. On histological evaluation of the lenses from fetuses with/without gross findings, primary lens fiber hypertrophy (swelling) and degeneration were observed across vehicle- and JNJ-42165279-exposed fetuses. In a follow-up study to investigate the progression or resolution of the fetal lens changes, animals exposed to suprapharmacological doses of JNJ-42165279 in utero had higher incidence of nuclear cataracts as detected via slit-lamp ophthalmic examinations on postnatal days 18 to 21 and 35 to 41. No histologic correlates for these cataracts were identified. We conclude that fetal primary lens fiber hypertrophy and nuclear cataracts at ophthalmology, are common background changes in this rat strain that are exacerbated by in utero exposure to the FAAH inhibitor JNJ-42165279.

01 Apr 2021·NeuropsychopharmacologyQ1 · MEDICINE

The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: a double-blind, randomized, placebo-controlled proof-of-concept study

Q1 · MEDICINE

Article

Author: Simmons, W Kyle ; Drevets, Wayne C ; Saad, Ziad S ; Grunfeld, Jennifer ; Pemberton, Darrel J ; Liebowitz, Michael R ; Schmidt, Mark E ; Van Nueten, Luc ; Palmer, James A ; Stein, Murray B ; Van Hove, Ilse ; Van Der Ark, Peter

AbstractJNJ-42165279 is a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of fatty acid amides (FAA) including anandamide (AEA), palmitoylethanolamide (PEA), and N-oleoylethanolamide (OEA). We assessed the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with JNJ-42165279 in subjects with social anxiety disorder (SAD). This was a multicenter, double-blind, placebo-controlled study randomizing subjects to 12 weeks of treatment with either JNJ-42165279 (25 mg daily) or placebo (PBO). The primary endpoint was the change in the Liebowitz Social Anxiety Scale (LSAS) total score from baseline to end of study. Secondary endpoints included the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Rating Scale (HDRS17), and the Clinical Global Impression-Improvement (CGI-I). Samples were collected for plasma concentration of AEA, PEA, OEA, and JNJ-42165279. A total of 149 subjects were enrolled with a mean baseline LSAS total score of 102.6 (SD 16.84). The mean change from baseline (SD) in LSAS total score at week 12 was numerically greater for JNJ-42165279: −29.4 (27.47) compared to PBO: −22.4 (23.57) but not significant. The percentage of subjects with ≥30% improvement from baseline in the LSAS total score was significantly higher for JNJ-42165279 (42.4%) compared to PBO (23.6%) (p value = 0.04). The percentage of subjects with a CGI-I score of much or very much improved was also significantly higher for JNJ-42165279 (44.1%) than for PBO (23.6%) (p value = 0.02). The drug was well tolerated. JNJ-42165279 appears to elicit an anxiolytic effect in subjects with SAD although trough concentrations with 25 mg once daily appeared to be insufficient to completely inhibit FAAH activity which may have led to suboptimal efficacy. ClinicalTrials.gov Identifier: NCT02432703.

01 Apr 2021·NeuropsychopharmacologyQ1 · MEDICINE

The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial

Q1 · MEDICINE

Article

Author: Stein, Murray B ; Chaplan, Sandra R ; Halter, Robin ; Simmons, Alan N ; Risbrough, Victoria B ; Paulus, Martin P

Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), prolongs the regulatory effects of endocannabinoids and reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. However, the neural systems underlying this modulation are poorly understood. A single site, randomized, double-blind, placebo-controlled, parallel study was conducted with 43 subjects assigned to receive once daily dosing of either placebo (n = 21) or JNJ-42165279 (100 mg) (n = 22) for 4 consecutive days. Pharmacodynamic effects were assessed on the last day of dosing and included evaluation of brain activation patterns using BOLD fMRI during an (1) emotion face-processing task, (2) inspiratory breathing load task, and (3) fear conditioning and extinction task. JNJ-42165279 attenuated activation in the amygdala, bilateral anterior cingulate, and bilateral insula during the emotion face-processing task consistent with effects previously observed with anxiolytic agents. Higher levels of anandamide were associated with greater attenuation in bilateral anterior cingulate and left insula. JNJ-42165279 increased the activation during anticipation of an aversive interoceptive event in the anterior cingulate and bilateral anterior insula and right inferior frontal cortex. JNJ-42165279 did not affect fear conditioning or within-session extinction learning as evidenced by a lack of differences on a subjective and neural circuit level. Taken together, these results support the hypothesis that JNJ-42165279 at this dose shares some effects with existing anxiolytic agents in dampening response to emotional stimuli but not responses to conditioned fear.

100 Deals associated with JNJ-42165279

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15173

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 2	RU	Janssen Research & Development LLC	07 Oct 2015
Depressive Disorder, Major	Phase 2	UA	Janssen Research & Development LLC	07 Oct 2015
Depressive Disorder, Major	Phase 2	GB	Janssen Research & Development LLC	07 Oct 2015
Depressive Disorder, Major	Phase 2	MD	Janssen Research & Development LLC	07 Oct 2015
Phobia, Social	Phase 2	CA	Janssen Research & Development LLC	11 Jun 2015
Phobia, Social	Phase 2	US	Janssen Research & Development LLC	11 Jun 2015
Phobia, Social	Phase 2	AU	Janssen Research & Development LLC	11 Jun 2015
Phobic Disorders	Phase 2	US	Janssen Research & Development LLC	11 Jun 2015
Phobic Disorders	Phase 2	CA	Janssen Research & Development LLC	11 Jun 2015
Phobic Disorders	Phase 2	AU	Janssen Research & Development LLC	11 Jun 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02498392 (CTgov)	Phase 2	Anxiety Disorders \| Depressive Disorder, Major	161	placebo (Placebo)	dgryacujkh(xbwjagzrjl) = icbiwipbmv fwiuvkrtjf (tvubwypyqh, xxwhyvfglj - qalkjyxrpe) View more	-	07 Apr 2022
NCT02498392 (CTgov)	Phase 2	Anxiety Disorders \| Depressive Disorder, Major	161	JNJ-42165279 (JNJ-42165279 25 mg)	dgryacujkh(xbwjagzrjl) = icclsupnic fwiuvkrtjf (tvubwypyqh, srnsfhbggr - awqrpoymfu) View more	-	07 Apr 2022
NCT02432703 (CTgov)	Phase 2	Phobia, Social \| Phobic Disorders	150	Placebo	omkalnuelj(xsgmvhbepn) = afphbtgfxz anjqrsitac (xdkqjsstuj, mgckfwdbjf - kcaqkarams) View more	-	02 Sep 2021