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

使用新型尼古丁替代疗法治疗吸烟 Cessati 的试点 PK 研究

• 批准号: 8396406
• 负责人: John McCarty
• 金额: $ 25.89万
• 依托单位: PHARMACEUTICAL PRODUCTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8396406
• 关键词: Adverse event; Area; Businesses; California; Cessation of life; Characteristics; Cigarette; Clinic; Clinical; Clinical Research; Collaborations; Country; Cross-Over Studies; Crossover Design; Data; Development; Disease; Drug Delivery Systems; Drug Kinetics; Environmental Tobacco Smoke; Expenditure; Exposure to; Foundations; Friends; Funding; Goals; Grant; Health; Human; Income; Institutional Review Boards; International; Legal patent; Marketing; Medical; Monitor; Nicotine; Oral; Participant; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Phase; Physicians; Plasma; Production; Productivity; Protocols documentation; Public Health; Questionnaires; Randomized; Research; Research Design; Research Institute; Research Project Grants; Route; Scientist; Small Business Technology Transfer Research; Smoker; Smoking; System; Therapeutic; Time; Tobacco; Tobacco use; Visual; Work; World Health Organization; analog; arm; cigarette smoking; commercialization; comparative; cost; craving; design; disability; experience; improved; innovation; interest; nicotine craving; nicotine replacement; novel; open label; preference; premature; primary outcome; product development; programs; quality assurance; satisfaction; secondary outcome; smoking cessation; trend

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.

描述(由申请人提供)：拟议的概念验证研究寻求第一阶段STTR资金，以支持在健康吸烟者中进行新型尼古丁替代疗法(NRT)试点药代动力学(PK)试验。尽管科学家和临床医生呼吁改善NRT，特别是一种作用更快的NRT，类似于吸烟产生的尼古丁药代动力学，但NRT领域几乎没有产品开发。关于这本小说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，将新型NRT与非处方含片进行比较。产品性能的差异也将根据渴望满足感和产品偏好标准进行评估。正式的产品稳定性数据也将在计划中的商业集装箱封闭系统中获得。Friends Research Institute(FRI)[非营利研究机构]和Pharmtics Productions Inc.(PPI)[营利性小企业]之间的合作代表了一种伙伴关系，利用了各自组织的互补优势和专业知识。PPI的成立是为了促进药物输送的创新，并帮助制药公司获得市场对其治疗产品的批准。PPI是这部小说NRT的专利持有人。FRI拥有完善的拨款和研究管理、机构审查委员会和强大的质量保证体系，为开展严格的科学研究提供了理想的机构合作伙伴。在这项申请中，Fri的科学家和医生将在加利福尼亚州托兰斯的Fri诊所进行试点PK研究。Neal Benowitz博士已经同意在他的加州大学旧金山分校的实验室进行生物分析工作。为这一项目提供资金将推进三个目标。首先，资金将是这种新型NRT进一步开发的基础，它将确认PK类似于吸烟获得的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、渴望信息、产品性能标准和稳定性数据，我的公司需要这些数据来吸引公司合作伙伴进行商业化。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将提供一个真正未得到满足的临床需求，作为一种安全、方便、廉价的戒烟疗法，它可以满足吸烟者对尼古丁的渴望，而目前的戒烟疗法无法做到这一点。因此，它有可能成为戒烟治疗的突破性产品。这种产品将通过减少烟草消费和与吸烟相关疾病的治疗相关的巨额成本，为公众健康带来重大好处。烟草使用是最可预防的疾病、残疾和死亡原因。根据世界卫生组织(WHO)的数据，吸烟每年导致约500万人死亡--相当于每61/2秒就有一名现任或前任吸烟者死于与烟草有关的疾病9。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9。即使新型NRT没有像预期的那样成为突破性产品，临床医生在戒烟治疗方面也将多出一支有效的箭，这对人类健康来说是更好的。 公共卫生相关性：这项先导性药代动力学(PK)是一项概念验证研究，旨在证实这种新型尼古丁替代疗法(NRT)的PK类似于吸烟获得的PK；科学家和临床医生认为这将是戒烟治疗的重大改进。此外，对该产品性能的初步评估将通过将这种新型NRT与最近批准的NRT片剂进行比较来确定。除了比较PK，两款产品还将在尼古丁渴求满足度和产品偏好特征方面进行比较。这种新颖的NRT承诺为吸烟者提供真正未得到满足的临床需求，即安全、方便、廉价的戒烟疗法，以满足他们对尼古丁的渴望。

项目成果

Novel rapid-acting sublingual nicotine tablet as a cigarette substitution strategy.

新型速效舌下含尼古丁片作为香烟替代策略。

• DOI: 10.1007/s00213-022-06171-z
• 发表时间: 2022
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: Rose,JedE;Behm,FrederiqueM;Botts,TanaiaL;Botts,DavidR;Willette,PerryN;Vocci,Frank;McCarty,John
• 通讯作者: McCarty,John