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

• 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
• 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

 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，如糖尿病神经病中所发生的那样。神经性疼痛很难治疗，许多患者的疼痛是现有治疗方法难以治愈的。 Omnitram 是 Syntrix 开发的一种新型混合机制镇痛药，由 O-去甲基曲马多的 (-) 和 (+) 对映体组成。 (+)-对映体是一种有效的 µ-阿片受体激动剂，而 (-)-对映体是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阿片类药物辅助联合疗法，预计滥用可能性较低。 O-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，但与曲马多相反，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。在接受多种药物治疗的患者中，CYP2D6 PM 状态的“现实”发生率高达三分之一。因此，Omnitram 是开发“改进的曲马多”的一个机会，该药物对所有患者都有效，无论其 CYP2D6 代谢状态如何。 Omnitram 成功完成了 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。该快速通道申请旨在通过证明对糖尿病神经病变引起的神经性疼痛患者的镇痛功效，进一步推动 Omnitram 计划的成功。 Cochrane 系统评价得出的结论是，曲马多是治疗神经性疼痛的有效方法，其疗效与报道的抗抑郁药和抗惊厥药相似。 Omnitram 提供与曲马多相同的净药理学，因此预计可有效治疗神经性疼痛。