Pilot PK Study with a Novel Nicotine Replacement Therapy for Smoking Cessati

描述（由申请人提供）：拟议的概念验证研究寻求I期STTR资助，以支持在健康吸烟者中进行新型尼古丁替代疗法（NRT）中试药代动力学（PK）试验。尽管科学家和临床医生呼吁改进NRT，特别是一种类似于吸烟产生的尼古丁药代动力学的更快的NRT，但在NRT领域的产品开发很少。这种新颖NRT的初步PK数据表明，PK类似于吸烟获得的PK。试点PK研究被设计为一项开放标签、随机、双向交叉研究，比较新型NRT和非处方含片。产品性能的差异也将评估渴望满意度和产品偏好标准。正式的产品稳定性数据也将在计划的商用集装箱封闭系统中获得。Friends研究所（FRI）[非营利性研究机构]和制药生产公司（PPI）[营利性小企业]之间的合作代表了一种利用各自组织的互补优势和专业知识的伙伴关系。PPI的成立是为了促进药物输送的创新，并协助制药公司获得其治疗产品的市场批准。PPI是这种新型NRT的专利持有人。FRI为开展严谨的科学研究提供了理想的机构合作伙伴，拥有完善的资助和研究管理、机构审查委员会和健全的质量保证体系。在这项申请中，FRI的科学家和医生将在加利福尼亚州托伦斯的FRI诊所进行试点PK研究。尼尔·贝诺维茨博士已经同意在他的UCSF实验室进行生物分析工作。这个项目的资金将推进三个目标。首先，资金将是进一步开发这种新型NRT的基础，通过确认从吸烟中获得的PK，它减少了渴望并具有理想的产品性能属性。其次，拟议研究的结果将提供药代动力学数据、渴求信息、产品性能标准和稳定性数据，我的公司需要对其商业化的企业合作伙伴感兴趣。第三，拟议研究的结果将为第二阶段研究计划提供基础，该计划将侧重于获得市场批准的监管要求。这种新颖的NRT将作为一种安全、方便、廉价的戒烟治疗药物，满足吸烟者对尼古丁的渴望，这是目前戒烟治疗无法做到的，它将提供一个真正未被满足的临床需求。因此，它有可能成为戒烟治疗的突破性产品。这种产品通过减少烟草消费和与治疗与吸烟有关的疾病有关的巨额费用，将对公众健康大有裨益。烟草使用是导致疾病、残疾和死亡的最可预防的原因。根据世界卫生组织（世卫组织）的数据，烟草使用每年导致约500万人死亡，或相当于每6.5秒就有一名现在或以前的吸烟者死于与烟草有关的疾病。如果目前的趋势继续下去，到2030年这一数字将达到800万，其中80%的过早死亡发生在低收入和中等收入国家。即使这种新型的NRT没有像预期的那样成为突破性的产品，临床医生也将在戒烟治疗的箭筒里多一支有效的箭，这对人类健康更有好处。

DESCRIPTION (provided by applicant): The proposed Proof of Concept Study seeks Phase I STTR funding to support a novel nicotine replacement therapy (NRT) pilot pharmacokinetic (PK) trail in healthy smokers. Very little by way of product development has occurred in the NRT field despite scientists' and clinicians' pleas for improved NRTs, specifically for a faster-acting NRT that resembles nicotine pharmacokinetics as produced by cigarette smoking 4-6. Preliminary PK data on this novel NRT suggests that the PK resembles that obtained from smoking a cigarette. The pilot PK study is designed as an open-label, randomized, 2-way crossover study comparing the novel NRT to the Over- the-Counter lozenge. Differences in product performance will also be evaluated for craving satisfaction and product preference criteria. Formal product stability data will also be obtained in the planned commercial container-closure-system. The collaboration between Friends Research Institute (FRI) [non-profit research institute] and Pharmaceutical Productions Inc. (PPI) [for-profit small business] represents a partnership that draws on complementary strengths and expertise of the respective organizations. PPI was formed to promote innovation in drug delivery and to assist pharmaceutical companies in obtaining market approval of their therapeutic products. PPI is the patent holder for this novel NRT. FRI provides an ideal institutional partner for conducting rigorous scientific research, with well-developed grants and research administration, an Institutional Review Board, and robust quality assurance systems. In this application, FRI scientists and physicians will perform the pilot PK study at the FRI clinic in Torrance, California. Dr. Neal Benowitz has kindly agreed to conduct the bioanalytical work at his UCSF lab. Funding for this project will advance three goals. First, funding will be fundamental to further development of this novel NRT by confirming the PK resembles that obtained from smoking cigarettes, that it reduces cravings and has desirable product performance attributes. Second, findings from the proposed study will provide pharmacokinetic data, craving information, product performance criteria, and stability data that my company needs to interest a corporate partner for its commercialization. Third, results of the proposed study will provide the foundation for a Phase II research program that will focus on the regulatory requirements for obtaining market approval. This novel NRT will provide for a real unmet clinical need as a safe, convenient, inexpensive smoking cessation therapy agent that satisfies a smoker's nicotine cravings, which current smoking cessation therapies fail to do. As such, it has potential to be a breakthrough product in smoking cessation therapy. Such a product would be a major benefit to public health by reducing tobacco consumption and the huge costs associated with treatment of smoking-related diseases. Tobacco use is the most preventable cause of disease, disability, and death. According to the World Health Organization (WHO), tobacco use results in about 5 million deaths annually - or, equivalently, every 61/2 seconds a current or former smoker dies from tobacco-smoking-related disease 9. If the current trend continues, that number will reach 8 million by 2030, with 80% of these premature deaths occurring in low- and middle-income countries 9. Even if the novel NRT does not turn out to be a breakthrough product as anticipated, the clinician will have one more effective arrow in the quiver for the treatment of smoking cessation, so much the better for human health. PUBLIC HEALTH RELEVANCE: This pilot pharmacokinetic (PK) is a Proof of Concept Study designed to substantiate that the PK from this novel nicotine replacement therapy (NRT) resembles that obtained from cigarette smoking; something that scientists' and clinicians' believe will be a major improvement in smoking cessation therapy. Further, an initial assessment of the product's performance will be determined by comparing this novel NRT to the lozenge, the most recently approved NRT. In addition to comparative PK, the two products will be compared with respect to nicotine craving satisfaction and product preference characteristics. This novel NRT promises to provide the smoker with a real unmet clinical need for a safe, convenient, inexpensive smoking cessation therapy that satisfies their nicotine cravings.