Civamide Nasal Spray for the Treatment of Postherpetic Neuralgia of the Trigemina

西维酰胺鼻喷雾剂治疗三叉神经带状疱疹后神经痛

• 批准号: 8545911
• 负责人: Scott B Phillips
• 金额: $ 19.56万
• 依托单位: WINSTON PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545911
• 关键词: Accounting; Adult; Adverse effects; Adverse event; Affect; Agreement; Area; Burn injury; Chronic; Clinical; Clinical Research; Cluster Headache; Communities; Controlled Study; Development; Disease; Disease Outbreaks; Dose; Double-Blind Method; Drug Formulations; Drug Interactions; Drug Kinetics; Elderly; Enrollment; Episodic Cluster Headaches; Esthesia; Face; Facial Neuralgia; Frequencies; Funding; Goals; Grant; Headache; Headache Disorders; Herpes zoster disease; Infection; Lead; Licensing; Measurable; Measures; Mediating; Medical; Migraine; Nerve; Nerve Endings; Neurologist; Neurotransmitters; Nose; Orphan Drugs; Outcome; Pain; Patient Care; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Population; Postherpetic neuralgia; Randomized; Rare Diseases; Research; Safety; Scalp structure; Secondary pain; Serious Adverse Event; Sleep; Sleep disturbances; Small Business Innovation Research Grant; Structure of mucous membrane of nose; Text; Therapeutic; Therapeutic Effect; Time; Trigeminal nerve structure; absorption; chronic pain; commercialization; diaries; effective therapy; experience; innovation; novel; novel strategies; phase 2 study; phase 3 study; primary outcome; programs; receptor; research and development; treatment duration

DESCRIPTION (provided by applicant): The project is the initial proof of concept clinical study of Civamide Nasal Spray for the treatment of postherpetic neuralgia (PHN) of the trigeminal nerve [(TN), a severely disabling facial pain syndrome]. Civamide Nasal Spray as a treatment for PHN of the [TN] has previously been granted orphan drug designation. If this study is successful in the treatment of PHN of the [TN], further clinical development will proceed, i.e., Phase 2 and Phase 3 studies to support the filing of a New Drug Application. Currently, all approved medications for treating PHN of the [TN] are systemically acting drugs. Civamide Nasal Spray is unique in that it exerts its therapeutic effect locally without systemic absorption [being detected in a pharmacokinetic study.8] The availability of a safe and effective medication for PHN of the [TN] for these patients, i.e., Civamide Nasal Spray, will thus fill an unmet medical need. Civamide, a TRPV-1 receptor modulator,1,2 is a medication [with a mechanism of action] that affects nerves by causing a depletion of neurotransmitters, thus making the nerve less able to transmit pain.25,26 PHN of the [TN] is a chronic condition characterized by extreme pain following herpes zoster infection, (commonly called shingles,) in the areas of the face and scalp which are innervated by the [TN].3,4,5 The [TN] also has superficial nerve endings in the nasal mucosa, which are the targets of Civamide Nasal Spray. By affecting these nerve endings the entire nerve's ability to transmit pain is reduced. This novel mechanism of action has been observed when Civamide Nasal Spray is applied to the nasal mucosa in subjects with headache disorders mediated by the [TN], e.g. migraine headaches and cluster headaches with resulting decreases in headache pain and frequency. This study is a 9 week, double-blind, vehicle-controlled study of adult subjects that have moderate to severe pain (a minimum of an average pain score of 4 on a 0-10 point scale) due to PHN of the [TN] for at least 12 months. The study is composed of a 1-week non-treatment Baseline Period during which subjects will be required to complete a daily diary assessing overall pain and sleep interference. The 1 week Baseline Period will be followed by a 6 week Double-Blind Treatment Period and a 2 week Observation Period. Subjects will be randomized 1:1, approximately [20] subjects per group. The primary outcome variable will be the change in the Average Daily PHN Pain Score from the Baseline Period to the last week of the Treatment Period. Adverse events will be recorded during the study.

描述(申请人提供)：该项目是西维胺鼻喷雾剂治疗三叉神经带状疱疹后神经痛(PHN)的初步概念验证临床研究[(TN)，一种严重致残的面部疼痛综合征]。作为治疗PHN的[TN]的西瓦胺鼻喷雾剂此前已被批准为孤儿药物。如果这项研究在治疗[TN]的PHN方面成功，将继续进行进一步的临床开发，即第二阶段和第三阶段研究，以支持新药申请的提交。目前，所有被批准用于治疗[TN]的PHN的药物都是具有全身作用的药物。西维胺鼻喷雾剂的独特之处在于，它在局部发挥治疗作用，而不会[在药代动力学研究中检测到]全身吸收。8]为这些患者提供一种安全有效的治疗[TN]PHN的药物，即西瓦胺鼻喷雾剂，将填补一个未满足的医疗需求 需要。希夫酰胺是一种TRPV-1受体调节剂，1，2是一种[具有作用机制]的药物，通过导致神经递质耗尽来影响神经，从而使神经更难传递疼痛。25，26[TN]的PHN是一种慢性疾病，其特征是面部和头皮受[TN]支配的带状疱疹感染后的极度疼痛(通常称为带状疱疹)。3，4，5[TN]在鼻黏膜中也有浅层神经末梢，这是希夫胺鼻腔喷雾的目标。通过影响这些神经末梢，整个神经传递疼痛的能力降低。这种新的作用机制已经被观察到，当西瓦胺鼻腔喷雾剂应用于患有由[TN]介导的头痛障碍的受试者的鼻黏膜时，例如偏头痛和丛集性头痛，结果是头痛疼痛和头痛频率的减少。这项研究是一项为期9周的双盲车辆对照研究，研究对象为成年受试者，他们因[TN]的PHN至少有12个月的中到重度疼痛(平均疼痛评分至少为4分)。这项研究由一周的非治疗基准期组成，在此期间，受试者将被要求完成每日日记，评估总体疼痛和睡眠干扰。在1周的基准期之后，将进行6周的双盲治疗和2周的观察期。受试者将以1：1的比例随机分配，每组约20名受试者。主要结果变量将是从基准期到治疗期最后一周的平均每日PHN疼痛评分的变化。研究期间将记录不良事件。