Phase II clinical evaluation of Omnitram in neuropathic pain

Omnitram 治疗神经病理性疼痛的 II 期临床评价

基本信息

批准号：
9317459
负责人：
STUART J KAHN
金额：
$ 65.72万
依托单位：
SYNTRIX BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9317459
关键词：
Absence of pain sensation Adjuvant Adopted Adverse effects Affect Agonist Analgesics Anticonvulsants Antidepressive Agents CYP2D6 gene Clinical Clinical Research Clinical Trials Combined Modality Therapy Complex Regional Pain Syndromes Cross-Over Studies Cross-Over Trials Cyclic GMP Diabetic Neuropathies Double-Blind Method Drug Kinetics Esthesia Exhibits France Funding Generic Drugs Germany Grant HIV Human Incidence Individual Investments Italy Japan Low Back Pain Malignant Neoplasms Metabolic Metabolism Methods Modeling National Institute of Drug Abuse Neuropathy Norepinephrine Opiate Addiction Opioid Opioid Receptor Oral Pain Pain management Painless Patient Care Patients Peripheral Nerves Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacotherapy Phase Physicians Placebo Control Placebos Plasma Population Postherpetic neuralgia Postoperative Period Production Public Health Randomized Randomized Clinical Trials Refractory Reporting Request for Proposals Resistance Risk Safety Sales Small Business Innovation Research Grant Spain Stimulus Symptoms Tablets Target Populations Testing Tramadol United Kingdom United States clinically relevant cost diabetic double-blind placebo controlled trial duloxetine economic cost effective therapy enantiomer experience genotoxicity improved inhibitor/antagonist interest mu opioid receptors novel painful neuropathy pregabalin programs public health relevance research clinical testing reuptake success systematic review

项目摘要

DESCRIPTION (provided by applicant): Neuropathic pain is caused by damage to the peripheral nerves, as occurs in diabetic neuropathy. Neuropathic pain is difficult to treat, and many patients have pain that is refractory to existing treatments. Omnitram is a novel mixed-mechanism analgesic developed by Syntrix that consists of the (-) and (+) enantiomers of O-desmethyltramadol. The (+)-enantiomer is a potent µ-opioid receptor agonist, while the (-)- enantiomer is a norepinephrine reuptake inhibitor that synergizes with the (+)-enantiomer. Omnitram is inherently an opioid-sparing opioid-adjuvant combination therapy that is predicted to have low abuse potential. O-desmethyltramadol is the primary metabolite (M1) of tramadol. Omnitram provides the same net pharmacology as tramadol, but in contrast to tramadol, does not require metabolism by cytochrome P450 2D6 (CYP2D6) for its activity (i.e. it is metabolism-independent). Individuals who are CYP2D6 poor metabolizers (PMs) fail to obtain pain relief from tramadol. The "real world" incidence of CYP2D6 PM status in patients on polypharmacotherapy is as high as 1 in 3. Omnitram is therefore an opportunity to develop an "improved tramadol" that is effective in all patients irrespective of their CYP2D6 metabolic status. Omnitram successfully completed a Phase 1b randomized, double-blind, placebo-controlled trial that demonstrated Omnitram provided significant analgesia compared to placebo in an experimental pain model in healthy subjects. This Fast-Track application aims to further the success of the Omnitram program by demonstrating analgesic efficacy in patients suffering from neuropathic pain due to diabetic neuropathy. A Cochrane systematic review concluded that tramadol is an effective treatment for neuropathic pain with efficacy similar to that reported for antidepressants and anticonvulsants. Omnitram provides the same net pharmacology as tramadol and is therefore predicted to be efficacious in treating neuropathic pain.

描述（由适用提供）：神经性疼痛是由对周围神经系统的损害引起的，如糖尿病神经病所发生的那样。神经性疼痛很难治疗，许多患者患有对现有治疗的疼痛。 Omnitram是一种由Syntrix开发的新型混合机制镇痛药，由O-甲基甲二醇的（ - ）和（+）对映体组成。（+） - 对映异构体是一种潜在的µ-阿片类综合剂，提供与曲马多相同的净药理学，但与曲马多相反，不需要细胞色素P450 2d6（CYP2D6）的活性来代谢（即它是代谢依赖性的）。 CYP2D6差代谢者（PMS）的个体无法从曲马多获得疼痛。因此，CYP2D6 PM在多药治疗中的“现实世界”事件高达3分之一。因此，Omnitram是开发“改进的Tramadol”的机会，无论其CYP2D6代谢状况如何，对所有患者均有效地有效。 Omnitram成功地完成了一个1B期随机，双盲，安慰剂对照试验，该试验证明了Omnitram在健康受试者的实验性疼痛模型中与安慰剂相比提供了明显的镇痛。这种快速轨道应用旨在通过证明糖尿病神经病引起的神经性疼痛的患者的镇痛效率来进一步取得成功的成功。 Cochrane系统评价得出的结论是，Tramadol是一种有效的神经性疼痛治疗方法，其有效性与报道的抗抑郁药和抗惊厥药相似。 Omnitram提供与Tramadol相同的净药理学，因此预计将有效地治疗神经性疼痛。