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：
8981655
负责人：
STUART J KAHN
金额：
$ 22.5万
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 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8981655
关键词：
Absence of pain sensation Adjuvant Adopted Adverse effects Affect Agonist Analgesics Anticonvulsants Antidepressive Agents Burn injury Clinical Research Clinical Trials Combined Modality Therapy Complex Regional Pain Syndromes Cross-Over Studies Cross-Over Trials Cyclic GMP Cytochrome P-450 CYP2D6 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 Marketing 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 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（由申请人提供）：神经性疼痛是由周围神经损伤引起的，如糖尿病神经病中发生的那样。神经性疼痛很难治疗，并且许多患者的疼痛是现有治疗方法难以治愈的。 Syntrix 开发的镇痛药由 O-去甲基曲马多 (O-desmethyltramadol) 的 (-) 和 (+) 对映体组成。 (+)-对映体是一种有效的镇痛剂。 µ-阿片受体激动剂，而 (-)- 对映体是一种去甲肾上腺素再摄取抑制剂，与 (+)-对映体具有协同作用，Omnitram 本质上是一种节省阿片类药物的联合疗法，预计滥用可能性较低。 -去甲基曲马多是曲马多的主要代谢物 (M1)，Omnitram 提供与曲马多相同的净药理学，但在与曲马多相比，其活性不需要细胞色素 P450 2D6 (CYP2D6) 的代谢（即，它是代谢独立的）。CYP2D6 弱代谢者 (PM) 无法从曲马多中获得疼痛缓解。接受多种药物治疗的患者中 CYP2D6 PM 状态的比例高达三分之一。因此，Omnitram 是开发“改进的“曲马多”对所有患者均有效，无论其 CYP2D6 代谢状态如何。Omnitram 成功完成了一项 1b 期随机、双盲、安慰剂对照试验，证明在健康受试者的实验性疼痛模型中，与安慰剂相比，Omnitram 提供了显着的镇痛效果。快速通道申请的目的是通过证明 Omnitram 项目对因糖尿病神经病变而患有神经性疼痛的患者的镇痛功效，以进一步取得成功。 Cochrane 系统。审查得出的结论是，曲马多是治疗神经性疼痛的有效方法，其功效与报道的抗抑郁药和抗惊厥药相似，其净药理学与曲马多相同，因此预计可有效治疗神经性疼痛。