A Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety, Tolerability, and Pharmacokinetics of JNJ-61393215 in Healthy Japanese Adult Male Subjects

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) after single dose administrations of JNJ-61393215 in Japanese healthy adult male participants.

Start Date29 Jan 2021

Sponsor / Collaborator

Janssen Pharmaceuticals, Inc.

NCT04080752

/ CompletedPhase 2

Double-Blind, Placebo-Controlled, Multi-Center Study Investigating the Efficacy, Safety, and Tolerability of JNJ-61393215 as Adjunctive Treatment in Adults With Major Depressive Disorder With Anxious Distress With Suboptimal Response to Standard Antidepressants

The purpose of this study is to evaluate the efficacy of JNJ-61393215 as adjunctive treatment compared to adjunctive placebo, as assessed by the change from baseline to week 6 on a 17-item Hamilton Depression Rating Scale (HDRS-17) in participants with major depressive disorder (MDD) with anxious distress with a score greater than or equal to (>=) 2 on item 26 or 27 of the Inventory of Depressive Symptomatology, Clinician Rating -30 (IDS-C30), who have a suboptimal response to current treatment with a standard antidepressant.

Start Date17 Sep 2019

Sponsor / Collaborator

Janssen Research & Development LLC

NL-OMON46054

/ CompletedNot Applicable

A Multi-cohort, Randomized Study in Healthy Subjects to Assess the Pharmacokinetics and Safety of Single and Multiple Ascending Doses of JNJ-61393215 (Suspension), and to Assess the Relative Bioavailability, and the Effect of Food on the Pharmacokinetics, of a New Solid Formulation (Capsules) of JNJ-61393215 - Orexin SAD MAD FE BA

Start Date03 Sep 2018

Sponsor / Collaborator

Janssen-Cilag International NV

100 Clinical Results associated with Tebideutorexant

100 Translational Medicine associated with Tebideutorexant

100 Patents (Medical) associated with Tebideutorexant

Literatures (Medical) associated with Tebideutorexant

01 Jun 2025·EUROPEAN NEUROPSYCHOPHARMACOLOGY

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

Article

Author: Zhou, Xianhuang ; Salvadore, Giacomo ; Samtani, Mahesh N ; Moyer, John A ; Drevets, Wayne C ; Kezic, Iva ; Dallas, Shannon ; Bleys, Cathy ; Schmidt, Mark E

The selective orexin-1 receptor antagonist JNJ-61393215 (tebideutorexant) has shown anti-panic properties in rodent and human panic-anxiety models. This double-blind, placebo-controlled, randomized, parallel-group, multicenter, phase 2a study evaluated the efficacy, safety, and tolerability of JNJ-61393215 in 222 patients (18-64 years) with major depressive disorder (MDD) with anxious distress who had experienced a suboptimal response to standard antidepressants. Eligible patients were randomized (1:1) to receive either adjunctive JNJ-61393215 (135 mg) or placebo, once daily. The primary objective was to evaluate the efficacy of JNJ-61393215 versus placebo, as assessed by the change from baseline to week 6 on the 17-item Hamilton Depression Rating Scale (HDRS₁₇). The key secondary objective was to evaluate the impact of JNJ-61393215 versus placebo on the severity of anxiety as measured by the change in the Hamilton Anxiety Rating Scale (HAM-A) from baseline to week 6. The study results for the full intent-to-treat analysis dataset did not show significant treatment effects of adjunctive treatment with JNJ-61393215 on either the primary endpoint (the least squares mean difference [standard error]: -0.67 [0.893]; p=0.2227) or the key secondary endpoint (0.23 [1.007]; p=0.5889). The safety results were consistent with the known safety profile of JNJ-61393215 with no serious adverse events reported during the study. 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.

01 Apr 2025·BIOORGANIC & MEDICINAL CHEMISTRY

Biosynthesis and structure assignment of a hydroxylated metabolite of the orexin-1 receptor antagonist JNJ-61393215

Article

Author: Salter, Rhys ; Lam, Wing ; Lim, Heng-Keang ; Zhou, Ronghui ; Steele, Jonathan ; Chen, Jie ; Kokubun, Tetsuo ; Phipps, Richard ; Dallas, Shannon ; Song, Fengbin

JNJ-61393215, a deuterated compound, is a selective OX1R antagonist. In both preclinical and clinical studies, a hydroxylated metabolite designated M54 was observed to be the most abundant metabolite in plasma. Screening of Hypha PolyCYPs®⁺ kit revealed PolyCYP 152 was the most proficient at producing M54 from JNJ-61393215 and subsequent scale up with PolyCYP 152 provided small but sufficient quantities of M54 for initial structure elucidation by NMR analyses. A microbial biosynthesis, using a Streptomyces strain from which PolyCYP 152 was genetically derived, provided gram quantities of M54. It allowed chemical epimerization of the chiral hydroxylated carbon of M54 and unequivocally established the metabolite's absolute stereo-configuration. 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.

01 Jun 2023·Journal of psychopharmacology (Oxford, England)

Pharmacological characterization of the selective orexin-1 receptor antagonist JNJ-61393215 in healthy volunteers

Article

Author: Zuiker, RGJA ; van Nueten, L ; Brooks, S ; Ziagkos, D ; Bleys, C ; Jacobs, GE ; van Gerven, JMA ; Moyer, JA ; Salvadore, G ; Drevets, WC ; Bonaventure, P

Background::

Up to 40% of patients suffering from anxiety disorders do not benefit from currently available pharmacological treatments. Overactivity of the orexin-1 receptor (OX1R) has been implicated in anxiety- and panic-related states.

Aim & methods::

We investigated the pharmacokinetics and characterized the pharmacodynamic (PD) profile of the OX1R antagonist JNJ-61393215 using a battery of central nervous system assessments investigating relevant functional domains such as alertness, attention, (visuo)motor coordination, balance, subjective effects and resting-state electroencephalography in a single ascending dose placebo-controlled study in doses from 1 to 90 mg inclusive, assessing PD up to 10 h after dosing, safety and pharmacokinetic in 48 healthy male subjects.

Results::

Average time to maximal plasma concentration ( Tmax) ranged between 1.0 and 2.25 h; average half-life ranged from 13.6 to 24.6 h and average maximum plasma concentration ranged from 1.4 to 136.8 ng/mL in the 1 and 90 mg groups, respectively. JNJ-61393215 did not demonstrate any statistically significant or clinically meaningful effects on any PD endpoint at any dose investigated at Tmax nor over the total period up to 10 h post-dose and was well tolerated. 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.

Conclusion::

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.

News (Medical) associated with Tebideutorexant

01 Aug 2023

·www.fiercebiotech.com

C4X sells full rights for substance use disorder drug to Indivior as part of refocus

Indivior said the deal is “aligned with our goal to build a strong and balanced pipeline focused on addiction treatments.” Indivior has paid 15.95 million pounds sterling ($20.4 million) to C4X Discovery for the full rights to the British biotech’s orexin-1 receptor antagonist being developed for substance use disorder. The two companies originally signed a deal back in 2018 that saw Indivior pay $10 million upfront and pledge up to $284 million in milestones if the asset, dubbed C4X3256, or a library of additional orexin-1 compounds included in the agreement proved successful. In return for the almost 16 million pound upfront payment today, C4X is surrendering the chance to ever cash in on those milestones. The Manchester, England-based biotech framed the decision as “part of C4XD’s evolution towards becoming an immuno-inflammatory therapeutics company.” “Indivior has made excellent progress with our orexin-1 candidate, and we are proud that they now wish to take this program fully in-house,” C4X Chief Business Officer Bhavna Hunjan said in the Aug. 1 release. “The agreement also provides an opportunity for us to crystallize value for the program early and underpins and accelerates our new strategy.” The company will use today’s funds alongside preclinical milestone payments from an IL-17 inhibitor licensed to Sanofi and a Nrf2 activator licensed to AstraZeneca to “further advance our newly focused portfolio towards and into the clinic.” C4X’s unpartnered portfolio centers around a MALT1 inhibitor, although the biotech said in the release that a partnering process for the asset has now been “initiated.” So far, C4X3256 is the only asset hailing from C4X that has made it into the clinic. The drug began a phase 1 multiple ascending dose trial in 2020, according to ClinicalTrials.gov. For Indivior, getting its hands on the full rights to C4X3256, which has been rechristened INDV-2000, is “aligned with our goal to build a strong and balanced pipeline focused on addiction treatments,” Chief Scientific Officer Christian Heidbreder, Ph.D., said in today’s release. “Importantly, we know the asset well, having worked closely with C4X Discovery for more than five years,” Heidbreder added. “We recognize its exciting potential and will continue to progress it as a novel approach to the treatment of opioid use disorder, as well as more broadly in substance use disorders.” Indivior isn’t the only one who sees potential in the candidate. In 2019, the U.S. National Institutes of Health’s program for opioid misuse and other long-term addictions handed over a $10.6 million grant to Indivior for development of the compound. Orexin regulates arousal, wakefulness and appetite, and focusing in on the neuropeptide has seen some regulatory success for insomnia. Idorsia, for example, secured the approval of its dual orexin receptor antagonist Quviviq as a sleeping pill. However, the Swiss biotech company had less luck trying to pursue a selective orexin-antagonist as a binge-eating disorder treatment, dropping the indication after a phase 2 trial fail.

Phase 1Phase 2Drug ApprovalLicense out/in

01 Aug 2023

·www.biospace.com

C4X Discovery Holdings PLC Announces Divestment of Orexin-1 to Indivior for £15.95m

This announcement contains inside information Strategic Divestment of C4XD's Orexin-1 Receptor Antagonist Programme to Indivior for £15.95 Million Sale encompasses all rights and enables immediate revenue recognition Non-dilutive proceeds to accelerate progress of immuno-inflammatory portfolio MANCHESTER, UK / ACCESSWIRE / August 1, 2023 / C4X Discovery Holdings plc (AIM:C4XD), a pioneering Drug Discovery company, today announces the execution of an asset purchase agreement for Indivior PLC (LSE: INDV) ("Indivior") to acquire the proprietary rights to C4XD's oral Orexin-1 receptor antagonist, C4X_3256 (INDV-2000) for substance use disorder, for £15.95 million. The completion of this non-dilutive strategic divestment forms part of C4XD's evolution towards becoming an immuno-inflammatory therapeutics company. As indicated in C4XD's April 2023 interim results, the Company's portfolio will focus on treatments for immuno-inflammatory diseases, including its lead small molecule α4β7 integrin inhibitor programme that aims to expand access to disease modifying treatments for patients with inflammatory bowel disease. The Company believes it can deliver greater value for shareholders by progressing these programmes further and intends to advance the α4β7 programme towards the clinic and move two further immuno-inflammatory programmes into Lead Optimisation. Under the terms of the agreement, the previous license agreement announced on 29th March 2018 will be terminated and Indivior will assume all rights related to the development and use of C4X_3256 (INDV-2000) and related compounds1. In 2019, Indivior received a $10.6 million grant for the development of C4X_3256 (INDV-2000) from the National Institutes of Health (NIH) HEAL (Helping to End Addiction Long-term) Initiative, which aims to improve prevention and treatment strategies for opioid misuse and addiction. Previously, C4X Discovery was eligible to receive potential milestone payments from Indivior that in aggregate could have reached a maximum of $284 million over time if all clinical development, regulatory and commercial goals were achieved, as well as royalties on net sales of C4X_3256 (INDV-2000). The Phase 1 multiple ascending dose (MAD) study is currently ongoing. Christian Heidbreder, Ph.D., CSO of Indivior PLC, said: "The acquisition of full rights to INDV-2000 is aligned with our goal to build a strong and balanced pipeline focused on addiction treatments. Importantly, we know the asset well, having worked closely with C4X Discovery for more than five years. We recognie its exciting potential and will continue to progress it as a novel approach to the treatment of Opioid Use Disorder, as well as more broadly in substance use disorders." Bhavna Hunjan, CBO of C4X Discovery, added: "Indivior has made excellent progress with our Orexin-1 candidate, and we are proud that they now wish to take this programme fully in-house. Their decision highlights the confidence they have in the programme and further underlines the power of our drug discovery expertise to produce valuable, commercially relevant, small-molecule drug candidates. The agreement also provides an opportunity for us to crystallise value for the programme early and underpins and accelerates our new strategy. This non-dilutive funding, alongside potential preclinical milestone payments from our licensing deals for C4XD immuno-inflammatory assets with Sanofi and AstraZeneca, will allow us to further advance our newly focused portfolio towards and into the clinic. With our internal portfolio progressing well and partnering on our MALT-1 programme initiated, we look to a strong future as an immuno-inflammation therapeutics Company." C4XD will not receive any further milestone or royalty payments from Indivior for the development or commercialisation of C4X_3256 (INDV-2000) - Ends - Contacts C4X Discovery Holdings Mo Noonan, Communications +44 (0)787 6444977 Panmure Gordon (UK) Limited (NOMAD and Broker) Freddy Crossley, Emma Earl (Corporate Finance) +44 (0)20 7886 2500 Rupert Dearden (Corporate Broking) C4X Discovery Media - Consilium Strategic Communications Mary-Jane Elliott, Chris Gardner, Matthew Neal +44 (0)203 709 5700 Notes to Editors: About C4X Discovery C4X Discovery ("C4XD") is a pioneering Drug Discovery company, combining scientific expertise with cutting-edge Drug Discovery technologies to efficiently deliver world‑leading medicines. We have a highly valuable and differentiated approach to Drug Discovery through our enhanced candidate molecule design and patient stratification capabilities, generating small molecule drug candidates across multiple disease areas focused on immuno-inflammation. Our commercially attractive portfolio ranges from early-stage target opportunities to late-stage Drug Discovery programmes and we have three commercially partnered programmes with one candidate in clinical development. For more information visit us at or follow us on twitter @C4XDiscovery. This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact rns@lseg.com or visit . SOURCE: C4X Discovery Holdings PLC View source version on accesswire.com:

License out/inPhase 1Acquisition

09 Dec 2019

·www.biospace.com

Altasciences appointed by Indivior to conduct Phase I clinical trial with C4XD’s Orexin-1 for treatment of Opioid Use Disorder

C4X Discovery Holdings plc is pleased to note the announcement that Altasciences has been selected by Indivior PLC to conduct “A Phase I, Double-Blind, Placebo-Controlled, Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of INDV-2000 Under Fasting and Fed Conditions in Healthy Volunteers”. C4X Discovery Holdings plc (“C4XD”, “C4X Discovery” or the “Company”) 9 December 2019 – C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, is pleased to note the announcement that Altasciences has been selected by Indivior PLC to conduct “A Phase I, Double-Blind, Placebo-Controlled, Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of INDV-2000 (C4X3256) Under Fasting and Fed Conditions in Healthy Volunteers ” . Dr Clive Dix, Chief Executive Officer of C4XD, said: “We are delighted that Altasciences has been appointed by Indivior to manage the clinical development of our molecule C4X3256, a non-opioid, highly-selective Orexin-1 Receptor Antagonist for the treatment of Opioid Use Disorder. With initiation of the Phase I clinical trial in sight, and Altasciences and Indivior’s expertise in the opioid field, we believe that our molecule has the potential to bring a new alternative treatment for patients suffering in what is a growing epidemic of opioid addiction. We follow the progress of our molecule in these trials with great anticipation.” # # # Below is the full announcement made today by Altasciences: ALTASCIENCES TO CONDUCT CLINICAL TRIAL FOR OPIOID USE DISORDER UNDER NIH FUNDING Laval, Quebec, December 9, 2019 – Altasciences has been selected by Indivior PLC to conduct “A Phase I, Double-Blind, Placebo-Controlled, Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of INDV-2000 (C4X_3256) Under Fasting and Fed Conditions in Healthy Volunteers” , pursuant to the National Institutes of Health (NIH) Funding Opportunity Announcement RFA-DA-19-002, dedicated to the development of medications to prevent and treat opioid use disorder and overdose. The grant was made to Indivior by the NIH in fiscal year 2019, to apply scientific solutions to reverse the national opioid crisis. In March 2018, Indivior entered into a license agreement with C4X Discovery Holdings PLC (C4X) whereby Indivior obtained exclusive global rights to develop and commercialize INDV-2000 (C4X_3256). The First-In-Human single-ascending-dose study will be conducted in two parts — Part I: double-blind, placebo-controlled, randomized, single-ascending-dose study in fasted condition. Part II: open-label, cross-over randomized, food interaction, single-dose study, which will be given once under fasting conditions and once at completion of a standard FDA high-fat breakfast. Altasciences offers extensive knowledge and expertise in the conduct of opioid use disorder trials and has numerous years of conducting NIH- and FDA-funded clinical studies, prior to undertaking this most recent research. “We look forward to partnering with Indivior and are proud to continue our long-standing contributions to advancements in the treatment of opioid use disorder. Since our first NIH grant award in 2012, we have consistently contributed to the body of knowledge in the field, and have helped accelerate development of these vital options for treating opioid addiction,” says Chris Perkin, Chief Executive Officer of Altasciences. About Altasciences Altasciences is a forward-thinking, mid-size contract research organization offering pharmaceutical and biotechnology companies of all sizes a proven, flexible approach to preclinical and early phase clinical studies, from lead candidate selection to proof of concept. For over 25 years, Altasciences has been integrating into clients’ projects to help support educated, faster, and more complete early drug development decisions. Altasciences’ full-service solutions include preclinical safety testing, clinical pharmacology, bioanalysis, program management, medical writing, biostatistics, and data management, all of which can be tailored to specific sponsor requirements. Altasciences… helping sponsors get better drugs to the people who need them, faster. # # # Contacts C4X Discovery Holdings Mo Noonan, Communications +44 (0)787 6444977 Panmure Gordon (UK) Limited (NOMAD and Broker) Freddy Crossley, Emma Earl (Corporate Finance) +44 (0)20 7886 2500 James Stearns (Corporate Broking) C4X Discovery Media – Consilium Strategic Communications Mary-Jane Elliott, Chris Gardner, Matthew Neal +44 (0)203 709 5700 Notes to Editors: About C4X Discovery C4X Discovery (C4XD) aims to create the world’s most productive Drug Discovery engine by using cutting-edge technologies and expertise to efficiently deliver best-in-class small-molecule medicines to clinical partners for the benefit of patients. The Company’s business model focuses on replenishing big pharma discovery pipelines and driving returns through revenue generating pre-clinical licensing deals. In 2018, C4XD successfully out-licensed a pre-clinical programme in addictive disorders to Indivior in a deal worth up to $294m. C4XD has a state-of-the-art suite of proprietary technologies across the Drug Discovery process and accesses further innovative capabilities and expertise through its growing network of partners. The Company is actively advancing its diverse pre-clinical discovery portfolio which is focused on inflammation, neurodegeneration and oncology (including immuno-oncology). Opportunities to maximise value from the portfolio are proactively driven by C4XD’s commercial division. The Company is led by a highly experienced management team and Board who have delivered significant value creation within the healthcare sector. For additional information please go to:

Phase 1License out/in

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 2	United States	Janssen Research & Development LLC	17 Sep 2019
Depressive Disorder, Major	Phase 2	Russia	Janssen Research & Development LLC	17 Sep 2019
Depressive Disorder, Major	Phase 2	Ukraine	Janssen Research & Development LLC	17 Sep 2019
Depressive Disorder, Major	Phase 2	United Kingdom	Janssen Research & Development LLC	17 Sep 2019
Generalized anxiety disorder	Phase 2	United States	Janssen Research & Development LLC	17 Sep 2019
Generalized anxiety disorder	Phase 2	Russia	Janssen Research & Development LLC	17 Sep 2019
Generalized anxiety disorder	Phase 2	Ukraine	Janssen Research & Development LLC	17 Sep 2019
Generalized anxiety disorder	Phase 2	United Kingdom	Janssen Research & Development LLC	17 Sep 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04080752 (CTgov)	Phase 2	Anxiety Disorders \| Depressive Disorder, Major \| Generalized anxiety disorder	222	Placebo	kmzodinuhl(fofduwoayu) = dfoitknlum tidnhroefa (hktifpqwiq, 0.66) View more	-	29 Sep 2022

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