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

描述（由申请人提供）：该项目是西丁胺鼻喷雾剂治疗三叉神经带状疱疹后神经痛（PHN）[（TN），一种严重致残性面部疼痛综合征]的初步概念验证临床研究。西丁胺鼻喷雾剂作为治疗PHN的[TN]之前已被授予孤儿药认定。如果本研究成功治疗了[TN]的PHN，则将进行进一步的临床开发，即，2期和3期研究，以支持新药申请的提交。目前，所有批准用于治疗[TN] PHN的药物都是全身作用药物。Civamide鼻喷雾剂的独特之处在于，它在局部发挥其治疗作用，而不会全身吸收[在药代动力学研究中检测到。8]对于这些患者，[TN]的PHN的安全有效药物的可用性，即，Civamide鼻喷雾剂，因此将填补一个未满足的医疗 需要的Civamide是一种TRPV-1受体调节剂，1，2是一种药物[具有作用机制]，通过引起神经递质的消耗来影响神经，从而使神经传递疼痛的能力降低。[TN]的PHN是一种慢性疾病，其特征是带状疱疹感染后的极度疼痛，（通常称为带状疱疹）。[TN]在鼻粘膜中也有浅表神经末梢，这是Civamide鼻喷雾剂的靶点。通过影响这些神经末梢，整个神经传递疼痛的能力降低。当将Civamide鼻喷雾剂应用于患有由[TN]介导的头痛疾病（例如偏头痛和丛集性头痛）的受试者的鼻粘膜时，观察到了这种新的作用机制，导致头痛和频率降低。本研究是一项为期9周、双盲、溶剂对照研究，受试者因[TN] PHN而出现中度至重度疼痛（0-10分量表上平均疼痛评分至少为4分）至少12个月。本研究由1周非治疗基线期组成，在此期间，受试者需要完成每日日志，评估总体疼痛和睡眠干扰。1周基线期之后为6周双盲治疗期和2周观察期。受试者将以1：1的比例随机分配，每组约[20]例受试者。主要结局变量为平均每日PHN疼痛评分从基线期至治疗期最后一周的变化。研究期间将记录不良事件。 公共卫生相关性：三叉神经PHN是一种主要影响老年人的疾病，3，4，5他们通常因其他医疗问题而服用其他药物。因此，有效治疗三叉神经PHN的药物（如西丁胺鼻喷雾剂）的可用性，不会被全身吸收，[如药代动力学研究13所示]，因此没有全身不良反应以及药物-药物相互作用[可用的全身药物]，将代表该人群中该疾病治疗的显著改善。

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. PUBLIC HEALTH RELEVANCE: PHN of the trigeminal nerve is a condition primarily affecting the elderly,3,4,5 who are usually on other medications for other medical problems from which they suffer. Thus, the availability of an effective medication for PHN of the trigeminal nerve, such as Civamide Nasal Spray, that is not systemically absorbed, [as demonstrated in a pharmacokinetic study13], and consequently is without both systemic adverse effects as well as drug-drug interactions [of available systemic medications] would represent a significant improvement in the treatment of this disease in this population.