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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要根据美国疾病控制中心的数据，14.2% 的美国成年人表示在任何时间段内都会出现偏头痛症状。三个月的时间，使它成为世界上第二大最严重的致残疾病。发作性（每月 2 – 14 天）或慢性（每月 15 天或以上），每次发作都伴有持续 4 - 72 小时的衰弱性疼痛和症状的结合偏头痛没有绝对的治愈方法。在美国和欧洲，与这些疾病相关的总体经济负担每年超过 $72B。然而，受影响的个人的个人“成本”远远超出了经济和身体上的痛苦，并反映在尽管如此，关系满意度、对照顾者的依赖增加以及工作和社会生产力的损失。通过 SPG 增加对三叉血管系统副交感神经激活的认识，大多数急性偏头痛治疗针对三叉神经血管激活的下游效应，包括 CGRP 受体和 5-HT 用于治疗偏头痛的非特异性止痛药（对乙酰氨基酚、非甾体抗炎药、阿片类药物）可能具有更直接的抗偏头痛作用。对三叉血管系统有伤害性作用，但它们对严重偏头痛症状缺乏足够的效力蝶腭神经节 (SPG) 阻滞手术直接针对三叉神经。并已被确定为一种有效的临床方法，可减少偏头痛症状，可作为经常根据需要进行治疗，且不会产生严重或成瘾的副作用。迄今为止，这些手术尚未得到实施。被认为是一线药物的有力替代品，因为它们 1) 需要由经过培训的人员进行管理医疗保健专业人员，2) 给药途径困难且不舒服，以及 3) 高供应和程序成本与单剂量药物相比，为了满足替代性偏头痛疗法日益增长的临床需求，我们由偏头痛护理专家、设备和药物开发商以及临床研究专家组成的团队创建了一个准确地将药物输送到上后鼻腔的技术，从而能够发展自我施用 SPG 块组合产品，可快速缓解疼痛，且不会产生严重和成瘾的副作用第一阶段 SBIR 的主要目标分为两个不同的目标：技术功效并评估自我管理的商业设计可行性——治疗的关键组成部分在第一个目标中，将设计和原型化影响鼻喷雾特性的组件。将使用替代鼻模型和激光衍射技术进行体外性能测试来测量并优化液滴大小、分布模式、药物输送速率、药物输送总量和鼻腔空腔沉积，确保局部药物应用于 SPG，同时满足基于功能和安全的规范关于当前药物输送装置的建议，目标 2 将重点关注为药物输送装置创建系统级设计。通过形成性人为因素评估提供输送装置，将不同群体的偏头痛患者聚集在一起，目标 2 的结论将是 FDA IND 前会议，以获得临床护理专业人员和关键意见领袖的支持。澄清监管途径以及临床前和临床测试，以支持成功的 NDA 申请。