tebideutorexant (JNJ-61393215) / J&J - LARVOL DELTA

Efficacy, safety, and tolerability of JNJ-61393215 (tebideutorexant), a selective orexin-1 receptor antagonist, as adjunctive treatment for major depressive disorder with anxious distress: A double-blind, placebo-controlled, randomized phase 2a study. (PubMed, Eur Neuropsychopharmacol) - P2 | "Overall, adjunctive treatment with an orexin-1 antagonist did not provide significant benefit relative to adjunctive placebo to patients with MDD and anxious distress. Trial registration number: ClinicalTrials.gov Identifier: NCT04080752."

Journal • P2a data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Biosynthesis and structure assignment of a hydroxylated metabolite of the orexin-1 receptor antagonist JNJ-61393215. (PubMed, Bioorg Med Chem) - "The biotransformation provided remarkably efficient methodologies for quick synthesis of the metabolite M54 with stereoselective hydroxylation on the deuterated unique 2-aza-[2.2.1]-bicycle core structure, for which structure assignment via classical synthesis of speculative structures would be challenging and resource-intensive. Moreover, the microbial biosynthesis provided M54 with high purity for ongoing preclinical studies."

Journal

Pharmacological characterization of the selective orexin-1 receptor antagonist JNJ-61393215 in healthy volunteers. (PubMed, J Psychopharmacol) - "The reported somnolence rate was 16.7% (which was attributable to the cohorts receiving 6 mg and higher doses) compared to 12.5% in placebo. This observation is in line with our knowledge about the OX1R in preclinical studies, where only inconsistent and non-dose-dependent changes in electroencephalography or other behavioural measures were observed under non-challenged conditions, potentially exemplifying the need for a challenged subject."

Journal • CNS Disorders • Mood Disorders • Psychiatry

Substituted [2.2.1] 2-azabicycles as selective orexin-1 antagonists: Discovery of JNJ-61393215 (ACS-Sp 2022) - "To understand these roles, Janssen initiated drug discovery programs to identify selective antagonists for the OX1 (SORA1) and OX2 (SORA2) receptors. This presentation will focus on the discovery of the SORA1 candidate, JNJ-61393215, which demonstrated panicolytic effects and an acceptable safety profile in Phase I clinical trials."

Mood Disorders • Psychiatry • Tobacco Addiction

A Study of JNJ-61393215 in the Treatment of Depression (clinicaltrials.gov) - P2; N=222; Completed; Sponsor: Janssen Research & Development, LLC; Recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study of JNJ-61393215 in Healthy Japanese Male Participants (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Janssen Pharmaceutical K.K.; Recruiting ➔ Completed

Clinical • Trial completion

A Study of JNJ-61393215 in the Treatment of Depression (clinicaltrials.gov) - P2; N=218; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial primary completion date: May 2021 ➔ Oct 2021

Clinical • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

[VIRTUAL] Anxiolytic Activity of the Orexin-1 Receptor Antagonist JNJ-61393215 in Preclinical and Human Panic Models (ASCP 2021) - "JNJ-61393215 showed anxiolytic activity in both preclinical and human anxiety CO2 challenge models without inducing sedation and with overall an acceptable tolerability profile. These results suggest that selectively inhibiting the OXR1 may be a novel therapeutic approach for anxiety disorders and potentially other psychiatric conditions Learning Objectives Understand the role of the orexin system in the pathophysiology of different psychiatric disorders Understand the translational data indicative of anxiolytic activity of the selective orexin-1 inhibitor JNJ-61393125"

Preclinical • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry

A Study of JNJ-61393215 in Healthy Japanese Male Participants (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Janssen Pharmaceutical K.K.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study of JNJ-61393215 in Healthy Japanese Male Participants (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Janssen Pharmaceutical K.K.

Clinical • New P1 trial

[VIRTUAL] Translational Evaluation of Novel Selective Orexin-1 Receptor Antagonist JNJ-61393215 in an Experimental Model for Panic in Rodents and Humans (ACNP 2020) - "To investigate the potential anxiolytic effects of JNJ-61393215 in humans, 39 healthy male subjects sensitive to the anxiogenic effects of 35% CO2 inhalation at screening were randomized to receive JNJ-61393215 25mg, JNJ-61393215 90mg, alprazolam 1mg bid or placebo for 7 days. Conclusions These results support the safety, tolerability, and anxiolytic effects of JNJ-61393215, and validate CO2 exposure as a translational cross-species experimental model to evaluate the therapeutic potential of novel anxiolytic drugs. Statistics To investigate the anxiolytic effects of JNJ-61393215 in the CO2 challenge model in humans the following statistical analyses were performed: Within each arm, the active treatment was compared to matched placebo on PSL-IV total score by using a linear mixed effects model, controlling for treatment, period and sequence as a fixed effect, participant as a random effect and baseline score as a covariate."

Preclinical • Alzheimer's Disease • CNS Disorders • Mood Disorders • Pain • Psychiatry

Translational evaluation of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for panic in rodents and humans. (PubMed, Transl Psychiatry) - "In phase-1 human studies, JNJ-61393215 at 90 mg demonstrated significant reduction (P < 0.02) in CO-induced fear and anxiety symptoms that were comparable to those obtained using alprazolam. The most frequently reported adverse events were somnolence and headache, and all events were mild in severity. These results support the safety, tolerability, and anxiolytic effects of JNJ-61393215, and validate CO exposure as a translational cross-species experimental model to evaluate the therapeutic potential of novel anxiolytic drugs."

Journal • Preclinical • Mood Disorders • Pain • Psychiatry

A Study of JNJ-61393215 in the Treatment of Depression (clinicaltrials.gov) - P2; N=218; Recruiting; Sponsor: Janssen Research & Development, LLC; Suspended ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Depression • Mood Disorders

A Study of JNJ-61393215 in the Treatment of Depression (clinicaltrials.gov) - P2; N=218; Suspended; Sponsor: Janssen Research & Development, LLC; Recruiting ➔ Suspended

Clinical • Trial suspension

A Study of JNJ-61393215 in the Treatment of Depression (clinicaltrials.gov) - P2; N=218; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open