A Phase I, Single-Center, Single-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Pharmacokinetics and Efficacy of Tezampanel for Opioid Withdrawal Syndrome in Treatment-Seeking Patients With Opioid Use Disorder

This study is examining the use of Tezampanel (TZP) for treatment of Opioid Withdrawal Syndrome (OWS) in participants with Opioid Use Disorder (OUD). Participants will receive TZP or placebo (PBO) daily on Days 2 - 7 during a 7-day inpatient stay at the research center to determine safety, pharmacokinetic (PK) assessment, and efficacy of TZP for OWS.

开始日期2024-10-16

申办/合作机构

Proniras Corp.初创企业

[+1]

NCT00567086 / Completed临床2期

A Double-Blind, Placebo-Controlled, Parallel Group Multicenter Study to Assess the Safety, Tolerance and Efficacy of a Single Subcutaneous Dose of TEZAMPANEL in Patients With Acute Migraine

To evaluate the effects of a single sc administration of TEZAMPANEL at one of three different dosage levels compared to placebo, employing traditional measures of efficacy and safety in the treatment of a single episode of acute migraine.

开始日期2006-10-01

申办/合作机构

TorreyPines Therapeutics, Inc.

100 项与替占帕奈相关的临床结果

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100 项与替占帕奈相关的转化医学

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100 项与替占帕奈相关的专利（医药）

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项与替占帕奈相关的文献（医药）

2024-02-01·The Journal of pharmacology and experimental therapeutics

Preventing Long-Term Brain Damage by Nerve Agent–Induced Status Epilepticus in Rat Models Applicable to Infants: Significant Neuroprotection by Tezampanel Combined with Caramiphen but Not by Midazolam Treatment

Article

作者: Apland, James P ; Rossetti, Katia ; Pidoplichko, Volodymyr I ; Braga, Maria F M ; De Araujo Furtado, Marcio ; Figueiredo, Taiza H ; Aroniadou-Anderjaska, Vassiliki

Acute exposure to nerve agents induces a peripheral cholinergic crisis and prolonged status epilepticus (SE), causing death or long-term brain damage. To provide preclinical data pertinent to the protection of infants and newborns, we compared the antiseizure and neuroprotective effects of treating soman-induced SE with midazolam (MDZ) versus tezampanel (LY293558) in combination with caramiphen (CRM) in 12- and 7-day-old rats. The anticonvulsants were administered 1 hour after soman exposure; neuropathology data were collected up to 6 months postexposure. In both ages, the total duration of SE within 24 hours after soman exposure was significantly shorter in the LY293558 plus CRM groups compared with the MDZ groups. Neuronal degeneration was substantial in the MDZ-treated groups but absent or minimal in the groups treated with LY293558 plus CRM. Loss of neurons and interneurons in the basolateral amygdala and CA1 hippocampal area was significant in the MDZ-treated groups but virtually absent in the LY293558 plus CRM groups. Atrophy of the amygdala and hippocampus occurred only in MDZ-treated groups. Neuronal/interneuronal loss and atrophy of the amygdala and hippocampus deteriorated over time. Reduction of inhibitory activity in the basolateral amygdala and increased anxiety were found only in MDZ groups. Spontaneous recurrent seizures developed in the MDZ groups, deteriorating over time; a small percentage of rats from the LY293558 plus CRM groups also developed seizures. These results suggest that brain damage can be long lasting or permanent if nerve agent-induced SE in infant victims is treated with midazolam at a delayed timepoint after SE onset, whereas antiglutamatergic treatment with tezampanel and caramiphen provides significant neuroprotection. SIGNIFICANCE STATEMENT: To protect the brain and the lives of infants in a mass exposure to nerve agents, an anticonvulsant treatment must be administered that will effectively stop seizures and prevent neuropathology, even if offered with a relative delay after seizure onset. The present study shows that midazolam, which was recently approved by the Food and Drug Administration for the treatment of nerve agent-induced status epilepticus, is not an effective neuroprotectant, whereas brain damage can be prevented by targeting glutamate receptors.

2023-04-01·Experimental biology and medicine (Maywood, N.J.)

Delayed tezampanel and caramiphen treatment but not midazolam protects against long-term neuropathology after soman exposure

Article

作者: Apland, James P ; Braga, Maria FM ; Rossetti, Katia ; Aroniadou-Anderjaska, Vassiliki ; Figueiredo, Taiza H

Prolonged status epilepticus (SE) can cause brain damage; therefore, treatment must be administered promptly after seizure onset to limit SE duration and prevent neuropathology. Timely treatment of SE is not always feasible; this would be particularly true in a mass exposure to an SE-inducing agent such as a nerve agent. Therefore, the availability of anticonvulsant treatments that have neuroprotective efficacy even if administered with a delay after SE onset is an imperative. Here, we compared the long-term neuropathology resulting from acutely exposing 21-day-old male and female rats to the nerve agent soman, and treating them with midazolam (3 mg/kg) or co-administration of tezampanel (10 mg/kg) and caramiphen (50 mg/kg), at 1 h postexposure (~50 min after SE onset). Midazolam-treated rats had significant neuronal degeneration in limbic structures, mainly at one month postexposure, followed by neuronal loss in the basolateral amygdala and the CA1 hippocampal area. Neuronal loss resulted in significant amygdala and hippocampal atrophy, deteriorating from one to six months postexposure. Rats treated with tezampanel–caramiphen had no evidence of neuropathology, except for neuronal loss in the basolateral amygdala at the six-month timepoint. Anxiety was increased only in the midazolam-treated rats, at one, three, and six months postexposure. Spontaneous recurrent seizures appeared only in midazolam-treated rats, at three and six months postexposure in males and only at six months in females. These findings suggest that delayed treatment of nerve agent–induced SE with midazolam may result in long-lasting or permanent brain damage, while antiglutamatergic anticonvulsant treatment consisting of tezampanel and caramiphen may provide full neuroprotection.

2020-11-01·Annals of the New York Academy of Sciences2区 · 综合性期刊

Electroencephalographic analysis in soman‐exposed 21‐day‐old rats and the effects of midazolam or LY293558 with caramiphen

2区 · 综合性期刊

Article

作者: Braga, Maria F. M. ; Figueiredo, Taiza H. ; Apland, James P. ; Aroniadou‐Anderjaska, Vassiliki ; De Araujo Furtado, Marcio

Abstract:

Acute nerve agent exposure induces status epilepticus (SE), which can cause brain damage or death. Research aiming at developing effective therapies for controlling nerve agent–induced SE is commonly performed in adult rats. The characteristics of nerve agent–induced SE in young rats are less clear; relevant knowledge is necessary for developing effective pediatric therapies. Here, we have used electroencephalographic (EEG) recordings and analysis to study seizures in postnatal day 21 rats exposed to 1.2 × LD50 of soman, and compared the antiseizure efficacy of midazolam (MDZ)—currently considered by the Food and Drug Administration to replace diazepam for treating SE in victims of nerve agent exposure—with that of LY293558, an AMPA/GluK1 receptor antagonist, administered in combination with caramiphen, an antimuscarinic with N‐methyl‐d‐aspartate receptor antagonistic properties. Prolonged SE developed in 80% of the rats and was reflected in behavioral seizures/convulsions. Both MDZ and LY293558 + caramiphen stopped the SE induced by soman, but there was a significant recurrence of seizures within 24 h postexposure only in the MDZ‐treated group, as revealed in the raw EEG data and their representation in the frequency domain using a fast Fourier transform and in spectral analysis over 24 hours. In contrast to the high efficacy of LY293558 + caramiphen, MDZ is not an effective treatment for SE induced by soman in young animals.

项与替占帕奈相关的新闻（医药）

2024-02-01

·Business Wire

Proniras Corporation Secures New Series B Financing and Names New Board Members to Support Phase 1 Study of Novel Treatment for Opiate Withdrawal

SEATTLE--( BUSINESS WIRE )--Proniras Corporation (“Proniras”), a clinical-stage biotechnology company developing novel small-molecule therapeutics for the treatment of substance use and specialty central nervous system disorders, today announced the successful completion of a $4.65 million funding round, marking a significant milestone in its ongoing Series B financing, which aims to secure up to $9 million. The new Series B funding will be used to support a Phase 1 clinical study of the Company’s lead program PRN-001-01 (tezampanel), a novel modulator of glutaminergic signaling designed to treat patients seeking to recover from opioid addiction and associated conditions. The Phase 1 study will apply the unique and groundbreaking mechanism of action of PRN-001-01 (tezampanel) to reduce brain over-activation in circuits involved in drug withdrawal, addiction, and mental illness without relying on direct stimulation or antagonism of the opioid system. PRN-001-01 (tezampanel) has the potential to provide significant improvement in the treatment of opiate withdrawal syndrome, opioid overdoses, and conversion to long term medications that can help patients addicted to opiates to achieve full remission from their illness. The Series B financing was co-led by funds managed by Accelerator Life Science Partners and ARCH Venture Partners, with participation from both new and existing investors, including Watson Fund, LP, WRF Capital (the investment vehicle for Washington Research Foundation), and other undisclosed investors. PRN-001-01 (tezampanel) is a novel small molecule compound that will be the first parenteral therapeutic to be evaluated for the treatment of symptoms associated with opiate withdrawal in a Phase 1 clinical study. Previously investigated for its potential in acute migraine therapy with positive outcomes observed in over 400 human subjects, PRN-001-01 (tezampanel) has also demonstrated encouraging results in various preclinical models of seizure disorders, suggesting the use of the drug in other therapeutic applications with high unmet medical need. Proniras licensed exclusive global rights to PRN-001-01 (tezampanel) from Eli Lilly and Company in 2017. In conjunction with the Series B financing, Proniras has appointed Steven Gillis, Ph.D., as Chairman and Atul Saran as an independent member to the Company’s Board of Directors. Dr. Gillis and Mr. Saran join Thong Q. Le, Senior Managing Director from Accelerator Life Science Partners, on the Proniras Board of Directors. With the insights gained throughout their professional careers, Dr. Gillis and Mr. Saran will positively impact guidance on the Company’s strategic decision-making and product development plans. In addition, their extensive networks in the industry will help Proniras on multiple fronts. Dr. Gillis has more than 30 years of experience in the life sciences industry and is focused on the evaluation of new life science technologies and also on the development and growth of ARCH's biotechnology portfolio companies. In addition to serving as Chairman of the Board for Proniras, he serves as a Director of multiple ARCH biotechnology portfolio companies, including Homology Medicines (FIXX), 48 Bio, Pheast Therapeutics, BE Biopharma, SonoThera, Dispatch Biotherapeutics, and Carrick Therapeutics. He serves as Chairman of Faraday Pharmaceuticals, eGenesis, HiberCell, hC Bioscience, Skylark Bio, Walden Biosciences, OncoResponse, Mozart Therapeutics, Bitterroot Bio, Vilya, TFC Therapeutics, and VBI Vaccines (VBIV). Dr. Gillis also serves as a director of Takeda Pharmaceuticals (TAK). Dr. Gillis was a founder and director of Corixa Corp. and served as the company's Chief Executive Officer from its inception and as its Chairman from 1999 until its acquisition in 2005 by GlaxoSmithKline. Prior to Corixa, Dr. Gillis held numerous positions at Immunex Corp., including founder and director. Dr. Gillis is a trained immunologist with over 300 peer-reviewed publications in the areas of molecular and tumor immunology. Atul Saran currently serves as Chief Executive Officer of IntegerBio, a privately held biotechnology company focused on developing immunovirology therapeutics. Prior to IntegerBio, Mr. Saran served in various roles at Emergent BioSolutions, a specialty biopharmaceutical company focused on opioid overdose, biodefense, and other public health threats, most recently as Executive Vice President & Chief Scientific and Development Officer with responsibility for the company's research, development, medical, and regulatory activities as well as corporate strategy and M&A. Before that, Mr. Saran was Emergent's General Counsel and Corporate Secretary with responsibility for corporate strategy, M&A, legal, public affairs, and government affairs. Prior to Emergent, Mr. Saran served as Senior Vice President and General Counsel at MacroGenics, and before that he held positions of increasing responsibility at MedImmune/AstraZeneca culminating with Senior Vice President of Corporate Development and Ventures for MedImmune and Vice President, Corporate Development & Strategy for AstraZeneca. Mr. Saran previously served as a Director on several boards, including Arriva, VentiRx, and Xencor. "We are honored to welcome Dr. Steve Gillis as our Chairman and Atul Saran as a new independent director to our Board of Directors," said Thong Q. Le, Senior Managing Director of Accelerator Life Science Partners, and CEO of Proniras. "Their wealth of knowledge and industry experience will be instrumental in guiding Proniras through its next phase of growth. We look forward to their leadership and contributions as we continue to advance Proniras through the next stages of product development." About Proniras Corporation Proniras Corporation is a clinical-stage biotechnology developing novel small-molecule therapeutics for the treatment of substance use and specialty central nervous system disorders. The Company’s lead program PRN-001-01 (tezampanel) is being clinical developed as a treatment option for opioid withdrawal and related disorders of addiction. Although effective treatments exist for opioid addiction, painful and difficult withdrawal is one of the primary reasons why current treatment fails, and relapse occurs. By alleviating the symptoms associated with opioid withdrawal, Proniras hopes to help patients successfully discontinue opioid usage and sustain an opioid-free life. Proniras was formed in 2017 by Accelerator Life Science Partners. For more information, please visit www.proniras.com .

临床1期高管变更并购

2008-06-04

·BioSpace

TorreyPines Therapeutics, Inc. Initiates Clinical Trial to Evaluate Analgesic Effect of Oral Prodrug of Tezampanel

LA JOLLA, Calif., June 4 /PRNewswire-FirstCall/ -- TorreyPines Therapeutics, Inc. today announced it has initiated a clinical trial to evaluate the analgesic effect of NGX426, the oral prodrug of its lead product candidate, tezampanel. The randomized, double-blind, placebo-controlled Phase I trial will enroll 18 healthy volunteers at a single center in the United States. The trial is designed to evaluate the compound's safety and tolerability and to assess the time of onset, magnitude and duration of its analgesic effect. Specifically, the study will evaluate the effect of NGX426 on hyperalgesia, an abnormally increased pain state, and allodynia, pain resulting from normally non-painful stimuli to the skin, induced by intradermal injections of capsaicin. The primary endpoint is subject self-report of spontaneous pain following the injection of capsaicin. "We believe there is a substantial commercial opportunity for NGX426 as a novel, oral analgesic," said Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines Therapeutics. "Data we have obtained in our ongoing Phase I maximum tolerated dose study demonstrate that the drug is well-tolerated at single doses up to and including 210 mg and that NGX426 is rapidly converted to tezampanel. Moreover, this capsaicin study, if successful, will enable us to further take advantage of the versatility of NGX426 and the overall tezampanel franchise." Subjects in the trial, which involves the recognized and validated capsaicin-induced pain model, will receive single doses of 90 mg and 150 mg of NGX426 versus placebo in a three-way crossover design. Tezampanel is the first AMPA/kainate-type glutamate receptor antagonist to be studied in clinical trials for chronic pain. Glutamate receptors mediate the functioning of glutamate, an important excitatory neurotransmitter. While normal glutamate production is essential, excess glutamate production, either through injury or disease, can have a range of pathological effects. By acting at both the AMPA and kainate receptor site to competitively block the binding of glutamate, tezampanel and its oral prodrug, NGX426, have the potential to treat a number of diseases and disorders. These include migraine and other forms of chronic pain such as neuropathic pain, muscle spasticity and rigidity, thrombosis, epilepsy, Parkinson's disease and a condition known as central sensitization, a persistent state of hypersensitivity to pain that is a core component of many pain conditions. About TorreyPines Therapeutics TorreyPines Therapeutics, Inc. is a biopharmaceutical company committed to providing patients with better alternatives to existing therapies through the research, development and commercialization of small molecule compounds. The company's goal is to develop versatile product candidates, each capable of treating a number of acute and chronic diseases and disorders such as migraine, chronic pain, muscle spasticity and rigidity, xerostomia and cognitive disorders. The company is currently developing four product candidates: two ionotropic glutamate receptor antagonists and two muscarinic receptor agonists. Further information is available at This press release contains forward-looking statements or predictions. Such forward-looking statements include, but are not limited to, statements regarding the potential for NGX426 as a novel, oral analgesic and the potential for tezampanel and NGX426 as treatments for migraine and other forms of chronic pain such as neuropathic pain, muscle spasticity and rigidity, thrombosis, epilepsy, Parkinson's disease and central sensitization. Such statements are subject to numerous known and unknown risks, uncertainties and other factors, which may cause TorreyPines' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements, including whether any preclinical studies or clinical trials conducted in the future, will prove successful, and if successful, whether the results can be replicated. These and other risks which may cause results to differ are described in greater detail in the "Risk Factors" section of TorreyPines' annual report on Form 10-K for the year ended December 31, 2007 and TorreyPines other SEC reports. The forward-looking statements are based on current information that is likely to change and speak only as of the date hereof. CONTACT: Company, Paul Schneider of TorreyPines Therapeutics, Inc., +1-858-623-5665, ext. 125, pschneider@torreypinestherapeutics.com; or Media, David Schull of Russo Partners, LLC, +1-212-845-4271, david.schull@russopartnersllc.com; or Investors, Rhonda Chiger of Rx Communications, +1-917-322-2569, rchiger@rxir.com, both for TorreyPines Therapeutics, Inc.

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KEGG	Wiki	ATC	Drug Bank
D06656	替占帕奈	-	DB06354

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性偏头痛	临床2期	美国	TorreyPines Therapeutics, Inc.	2006-10-01
阿片相关性障碍	临床1期	美国	Proniras Corp.初创企业	2024-10-16
物质戒断综合征	临床1期	美国	Proniras Corp.初创企业	2024-10-16

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


SFN2012	N/A	-	-	LY293558 15mg/kg	鬱廠遞選蓋範積窪顧積(鹽顧構鹽鹽壓襯膚顧艱) = 艱蓋艱簾淵獵繭衊淵襯夢願獵顧艱顧窪壓餘築 (窪獵衊積醖簾鹽艱鏇鬱 ) 更多	积极	2012-10-16
SFN2012	N/A	-	-	LY293558 20mg/kg	鬱廠遞選蓋範積窪顧積(鹽顧構鹽鹽壓襯膚顧艱) = 鹽觸廠糧衊鬱齋膚壓觸夢願獵顧艱顧窪壓餘築 (窪獵衊積醖簾鹽艱鏇鬱 ) 更多	积极	2012-10-16
SFN2010	N/A	-	-	LY293558	遞廠顧網艱鑰膚衊蓋糧(鑰範廠醖壓網範鹹鑰遞) = 選範鏇遞襯窪糧遞膚襯獵糧壓鹽壓窪製鹹壓網 (獵淵醖簾鬱糧製選淵製 ) 更多	-	2010-11-13