Development of an intranasal, direct to nerve treatment for headache disorders

开发鼻内、直接神经治疗头痛疾病

• 批准号: 10382876
• 负责人: Jonathan G Beckwith
• 金额: $ 33.69万
• 依托单位: OLFAX, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382876
• 关键词: Acetaminophen; Acute; Acute pain management; Address; Adoption; Adult; Adverse effects; Advisory Committees; Aerosols; Affect; Ambulatory Care; Analgesics; Anatomy; Anesthetics; Anterior nares; Brain; Calcitonin-Gene Related Peptide Receptor; Caregivers; Caring; Catheters; Centers for Disease Control and Prevention (U.S.); Characteristics; Chronic; Clinic; Clinical; Clinical Research; Collection; Custom; Dependence; Deposition; Development; Devices; Diagnosis; Disease; Dose; Drug Delivery Systems; Emotional; Ensure; Environment; Europe; Evaluation; Family; Feedback; Financial Hardship; Focus Groups; Formulation; Ganglia; Gossypium; Hand; Headache Disorders; Health Professional; Healthcare Systems; Helping to End Addiction Long-term; Home; Hour; Human; In Vitro; Individual; Inferior nasal concha; Intranasal Administration; Lasers; Lead; Leisures; Liquid substance; Measures; Mechanics; Medical; Medication Management; Methods; Migraine; Nasal cavity; National Institute of Neurological Disorders and Stroke; Nerve; Neurologic Symptoms; Nociception; Non-Steroidal Anti-Inflammatory Agents; Nose; Occupational; Opioid; Oral; Pain; Pain management; Patients; Pattern; Pharmaceutical Preparations; Phase; Population; Preclinical Testing; Procedures; Productivity; Quality of life; Recommendation; Regulatory Pathway; Reporting; Research; Risk; Risk Assessment; Route; Safety; Self Administration; Signal Transduction; Silicon; Small Business Innovation Research Grant; Somatosensory Cortex; Specialist; Specific qualifier value; Structure of mucous membrane of nose; Structure of trigeminal ganglion; Symptoms; System; Techniques; Technology; Testing; Therapeutic; Training; Translating; Treatment Efficacy; Trigeminal nerve structure; Work; World Health Organization; absorption; aerosolized; base; body position; clinical care; common treatment; cost; debilitating pain; design; experience; handheld equipment; in vitro testing; innovation; liquid formulation; mechanical force; medical specialties; meetings; migraine treatment; novel; oral pain; pain relief; pain signal; pain symptom; performance tests; prevent; procedure cost; propellant; prototype; research clinical testing; response; satisfaction; serotonin receptor; side effect; social; targeted treatment; therapy development; treatment strategy; verification and validation

PROJECT SUMMARY According to the US Centers for Disease Control, 14.2% of US adults report experiencing migraine symptoms within any given 3-month period, making it the second most disabling illness in the world. Diagnosed migraine is typically categorized as either episodic (2 – 14 days per month) or chronic (15 or more days per month), with each attack accompanied by a combination of debilitating pain and symptoms that persist between 4 - 72 hours. There is no absolute cure for migraine, and the overall financial burden associated with these disorders is more than $72B annually in the US and Europe. For individuals affected, however, the personal “costs” go well beyond financial and physical pain and are reflected in decreased relationship satisfaction, increased dependency on caregivers, and loss of work and social productivity. Despite increased recognition of parasympathetic activation of the trigeminovascular system through the SPG, the majority of acute migraine therapies target downstream effects of trigeminovascular activation, including CGRP receptors and 5-HT receptors. Nonspecific pain medications used in migraine (acetaminophen, NSAIDs, opioids) may have a more direct anti- nociceptive effect on the trigeminovascular system, but they either lack adequate potency for severe migraine symptoms or cause significant adverse effects. Sphenopalatine ganglion (SPG) block procedures directly target the trigeminal nerve and have been identified as an effective, in-clinic method for reducing migraine symptoms that can be administered as often as needed without the potential for severe or addictive side effects. To date, these procedures have not been considered a strong alternative to front-line medications due to their 1) Necessity for administration by a trained healthcare professional, 2) Difficult and uncomfortable route of administration, and 3) High supply and procedural costs compared to single-dose medication. In response to the increasing clinical need for alternative migraine therapies, our team comprised of migraine care specialists, device and drug developers, and clinical research specialists has created a technology for accurately delivering medication to the upper-posterior nasal cavity, enabling development of a self- administered SPG block combination product that provides rapid pain relief without the harsh and addictive side effects of existing medications. The Principal Objectives of this Phase I SBIR, separated into two distinct Aims, are to establish technical efficacy and evaluate commercial design feasibility for self-administration – a critical component for treatment efficacy. In the first aim, components affecting nasal spray characteristics will be designed and prototyped. Benchtop and in vitro performance testing will be conducted using a surrogate nasal cast and laser diffraction techniques to measure and optimize droplet size, distribution patterns, drug substance delivery rate, total drug substance delivered, and nasal cavity deposition to ensure local drug application to the SPG while meeting specifications for function and safety based on current recommendations for drug delivery devices. Aim 2 will focus on the creation of system-level designs for the delivery device through formative human factors evaluations that will bring together diverse groups of migraine patients, clinical care professionals, and key opinion leaders. The conclusion of Aim 2 will be an FDA pre-IND meeting to obtain clarification on the regulatory pathway and preclinical and clinical testing to support a successful NDA application.

项目摘要 根据美国疾病控制中心的数据，美国成年人中有14.2％的人报告在任何人中出现偏头痛症状 给定了三个月的时期，使其成为世界上第二大最残疾的疾病。诊断为偏头痛通常分类 作为一集（每月2 - 14天）或慢性（每月15天或以上），每次攻击都伴随 衰弱的疼痛和症状的结合在4-72小时之间。没有绝对治愈偏头痛， 在美国和欧洲，与这些疾病相关的总体财务燃烧每年超过$ 72B。为了 但是，受影响的个人“成本”远远超出了财务和身体痛苦，并反映在 尽管有关系满意度，对看护人的依赖增加以及工作损失和社会生产。 通过SPG，大多数 急性偏头痛疗法靶向三角血管激活的下游效应，包括CGRP受体和5-HT 受体。偏头痛（对乙酰氨基酚，NSAID，阿片类药物）中使用的非特异性止痛药可能具有更直接的抗抗 对三角血管系统的伤心效应，但它们要么缺乏适合严重偏头痛症状的效力 或引起严重的不良影响。蝶神经节（SPG）块手术直接针对三叉神经 并被确定为一种有效的临界方法，用于减少偏头痛症状 通常在需要的情况下没有潜力严重或加性副作用。迄今为止，这些程序还没有 由于其1）经过训练 医疗保健专业人员，2）困难和不舒服的管理途径，以及3）高供应和程序成本 与单剂量药物相比。为了响应替代性偏头痛疗法的临床需求日益增加 团队完成了偏头痛护理专家，设备和药物开发人员，临床研究专家创建了一个 用于准确将药物提供给上层鼻腔的技术，从而使自我发展 管理的SPG块组合产品可提供快速缓解疼痛，而无需造成伤害和上瘾的副作用 现有药物。该阶段I SBIR的主要目标分为两个不同的目标，是建立 技术效率并评估商业设计的自我管理可行性 - 治疗的关键组成部分 效率。在第一个目标中，将设计和原型设计影响鼻喷雾特性的组件。台式和 体外性能测试将使用替代鼻铸造和激光衍射技术进行测量 并优化液滴尺寸，分配模式，药物递送率，总药品和鼻腔 腔沉积以确保在满足功能和安全性规范的同时确保当地药物申请到SPG 根据目前的药物输送设备建议。 AIM 2将重点介绍为系统级设计的创建 通过形成性人为因素评估的交付设备，将偏头痛患者组成的潜水组群体 临床护理专业人员和关键意见领导者。 AIM 2的结论将是FDA预定的会议，以获得 澄清监管途径以及临床前和临床测试，以支持成功的NDA应用。