Treatment of Pain by Drug Aerosol Inhalation

药物气雾吸入治疗疼痛

• 批准号: 6999110
• 负责人: WILLIAM W SHEN
• 金额: $ 71.76万
• 依托单位: ALEXZA MOLECULAR DELIVERY CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999110
• 关键词: aerosols; analgesia; biomedical equipment development; biomedical equipment safety; cancer pain; cost effectiveness; drug abuse prevention; drug delivery systems; fentanyl; inhalation drug administration; method development; naloxone; portable biomedical equipment; surface coating; vapor

DESCRIPTION (provided by applicant): Breakthrough pain is a feared symptom afflicting the majority of cancer patients at some point in their illness. It is characterized by rapid onset, with pain intensity reaching excruciating level within several minutes, and brief duration (median duration approximately 30 minutes). Although commonly used, due to their delayed onset and long duration of action, oral opioids do not relieve breakthrough pain adequately and often result in excess plasma drug concentration after the pain has subsided, thus introduce adverse effects. A recently approved oral transmucosal fentanyl product has been commercially successful by marginally accelerating the onset of breakthrough pain treatment relative to oral opioids. However, there remains a substantial unmet need for a faster onset treatment with minimal side effects. The goal of this proposal is to develop an inhalation device for rapid systemic delivery of fentanyl, a potent opioid analgesic, for the treatment of breakthrough pain. The inhalation device applies a novel technology pioneered by Alexza MDC to generate a pure fentanyl aerosol appropriate for systemic delivery through the deep lung. Preliminary animal studies have shown rapid, IV-like, systemic delivery of several FDA-approved drugs to dogs using our technology. In Phase I of this grant, we will demonstrate the feasibility of incorporating this aerosol generation technology into a handheld, multi-dose delivery device with features ensuring patient safety and minimizing opioid abuse and diversion. In Phase II, we will determine the safety of fentanyl inhalation in animal toxicology studies, design and manufacture devices for use in clinical trials, and complete all product testing required prior to human use of our device. By the end of the grant period, we will be ready to initiate human testing of the multi-dose device. Eventual FDA approval of our fentanyl product will allow cancer patients to relieve breakthrough pain more effectively, thus improving their overall quality of life. In addition, the secure, convenient multi-dose device platform for rapid systemic delivery will likely find other valuable applications in clinical practices.

描述(由申请人提供)：突破性疼痛是一种令人恐惧的症状，在疾病的某个时候折磨着大多数癌症患者。它的特点是起病迅速，疼痛强度在几分钟内达到令人痛苦的水平，并且持续时间短(中位数持续时间约30分钟)。虽然常用，但由于其起效延迟和作用时间长，口服阿片类药物不能充分缓解突破性疼痛，往往导致疼痛消退后血浆药物浓度过高，从而产生不良反应。最近批准的一种口腔粘膜芬太尼产品在商业上取得了成功，相对于口服阿片类药物，它略微加速了突破性疼痛治疗的开始。然而，对于更快起效、副作用最小的治疗，仍有大量未得到满足的需求。这项提议的目标是开发一种吸入设备，用于快速全身给药芬太尼，一种有效的阿片类止痛剂，用于治疗突破性疼痛。该吸入器应用了Alexza MDC开创的一项新技术，以产生适合通过深肺全身给药的纯芬太尼气雾剂。初步的动物研究表明，使用我们的技术，几种FDA批准的药物可以快速、类似静脉注射的系统地输送到狗身上。在这笔赠款的第一阶段，我们将展示将这种气雾剂产生技术纳入手持式多剂量递送设备的可行性，该设备具有确保患者安全的特点，并将阿片类药物滥用和转移降至最低。在第二阶段，我们将在动物毒理学研究中确定芬太尼吸入的安全性，设计和制造用于临床试验的设备，并完成在人类使用我们的设备之前所需的所有产品测试。到授权期结束时，我们将准备开始对多剂量装置进行人体测试。最终FDA批准我们的芬太尼产品将使癌症患者能够更有效地缓解突破性疼痛，从而提高他们的整体生活质量。此外，用于快速全身给药的安全、方便的多剂量设备平台可能会在临床实践中找到其他有价值的应用。