SMART: A Breath-based Adherence Technology to Monitor HIV Microbicide Gel Use

SMART：基于呼吸的粘附技术，用于监测 HIV 杀菌剂凝胶的使用

• 批准号: 8659647
• 负责人: DONN MICHAEL DENNIS
• 金额: $ 31.13万
• 依托单位: XHALE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8659647
• 关键词: 2-butanol; Adherence; Behavior; Behavioral; Beverages; Biological Availability; Blinded; Cellular Phone; Clinical Investigator; Clinical Trials; Communication; Crossover Design; Data; Data Set; Databases; Development; Devices; Diagnostic; Directly Observed Therapy; Dose; Economics; Exhalation; FDA approved; Face; Faculty; Florida; Food; Gases; Gel; Generations; Glycerol; Gold; Grant; HIV; Health Insurance Portability and Accountability Act; Image; Individual; Industry; Ingestion; International; Internet; Intravaginal Administration; Legal patent; Licensing; Measurement; Measures; Microbicide Trials Network; Modeling; Monitor; National Institute of Mental Health; Oral; Participant; Pharmaceutical Preparations; Phase; Pilot Projects; Placebos; Positioning Attribute; Process; Production; Prophylactic treatment; Race; Reporting; Research Personnel; Route; Safety; Sales; Sampling; Self-Administered; Small Intestines; Stomach; Syringes; System; Technology; Tenofovir; Testing; Therapeutic; Time; Universities; Vagina; Wireless Technology; Woman; Work; Workplace; base; design; drug efficacy; manufacturing process; medication compliance; men; methylethyl ketone; microbicide; pre-clinical; public health relevance; quality assurance; rectal; residence; socioeconomics; time use; tool; trait

DESCRIPTION (provided by applicant): In HIV pre-exposure prophylaxis (PrEP) trials sub-optimal oral and microbicide adherence has precluded accurate estimation of drug efficacy. Measurement of adherence is a major, unmet challenge. Other objective measures of adherence in microbicide trials have been tested, but none measure the actual use of the product. We propose to rapidly develop an alternative, breath-based, adherence monitoring tool for investigators studying microbicide administration by leveraging technology already developed for oral dosing. Xhale has developed a breath-based technology, termed the SMART(R) (Self Monitoring and Reporting Therapeutics) Adherence System, to monitor individual subject, dose-by-dose, oral medication adherence in real-time using FDA-approved GRAS flavorants as the adherence enabling marker (AEM). The AEM (e.g., 2- butanol), which is easily and safely incorporated into drug product without altering its manufacturing processes or bioavailability, is rapidly absorbed in the stomach and small intestine, and metabolized to a volatile metabolite (e.g., 2-butanone) that quickly appears in breath. As the subject provides a breath sample by "blowing" directly into the SMART(R) device (miniature gas chromatograph, mGC), a facial picture is taken. Measurement of this metabolite(s) by the mGC unambiguously documents ingestion of oral drugs by a specific individual. Detailed trial data is stored locally i the mGC device and transmitted real-time using wireless or cellular router technology to a central data repository for analysis. The latter is an internet-based database for review by authorized individuals anywhere on the globe with an internet connection. SMART(R) is portable and designed to be self-administered by subjects. Although originally designed for oral drugs, SMART(R) can be easily adapted to document placement of microbicides. Using tenofovir (TFV) gel as a model agent, the aims of this grant are to construct a SMART(R) system optimized for microbicide applications: Aim 1. Using a crossover design in men (rectal route) and women (rectal and vaginal routes), identify an optimal AEM (type and dose) for microbicide applications. (Time: 0-12 months) Aim 2. Develop strategies (i.e., multiple-barrel syringe applicators) to effectively incorporate the optimal AEM into the placement of rectal and vaginal TFV gels that requires no change in their manufacturing processes, and preserves a favorable concentration-time profile of the breath marker. (Time: 12-24 months) Aim 3. Optimize the SMART(R) device for microbicide applications. (Time: 0-24 months) Measurement of microbicide adherence using SMART(R) would allow optimal analysis of PrEP trials by providing real-time actionable adherence data. By providing a "gold standard" tool to monitor microbicide adherence, SMART(R) could not only provide a superior trial dataset, but could also be used to identify behaviors associated with poor adherence and enable strategies to mitigate them. 1

描述（由申请人提供）：在HIV暴露前预防（PrEP）试验中，次优的口服和杀微生物剂依从性妨碍了对药物疗效的准确估计。依从性的测量是一个重大的、尚未解决的挑战。对杀微生物剂试验中依从性的其他客观衡量标准已经进行了测试，但没有一个衡量产品的实际使用情况。我们建议利用已经开发的口服给药技术，为研究杀微生物剂给药的研究人员快速开发一种替代的、基于呼吸的依从性监测工具。Xhale开发了一种基于呼吸的技术，称为SMART(R)（自我监测和报告治疗）依从性系统，使用fda批准的GRAS调味剂作为依从性使能标记（AEM），实时监测个体受试者，逐个剂量，口服药物依从性。AEM（例如，2-丁醇）很容易和安全地加入到药品中，而不会改变其制造工艺或生物利用度，在胃和小肠中迅速吸收，并代谢为挥发性代谢物（例如，2-丁醇），迅速出现在呼吸中。当受试者通过直接向SMART(R)设备（微型气相色谱仪，mGC）“吹”提供呼吸样本时，会拍摄面部照片。mGC对这种代谢物的测量明确地记录了特定个体口服药物的摄入情况。详细的试验数据本地存储在mGC设备中，并使用无线或蜂窝路由器技术实时传输到中央数据存储库进行分析。后者是一个基于互联网的数据库，供全球任何地方有互联网连接的授权个人审查。SMART(R)是便携式的，设计为受试者自行管理。虽然最初是为口服药物设计的，但SMART(R)可以很容易地用于记录杀微生物剂的放置。使用替诺福韦（TFV）凝胶作为模型剂，本赠款的目的是构建一个针对杀微生物剂应用进行优化的SMART(R)系统：目标1。在男性（直肠途径）和女性（直肠和阴道途径）中采用交叉设计，确定杀菌剂应用的最佳AEM（类型和剂量）。（时间：0-12个月）制定策略（即多管注射器），以有效地将最佳AEM纳入直肠和阴道TFV凝胶的放置，而不需要改变其制造工艺，并保持良好的呼吸标记物浓度-时间分布。（时间：12-24个月）优化SMART(R)设备的杀菌剂应用。（时间：0-24个月）使用SMART(R)测量杀微生物剂粘附性，通过提供实时可操作的粘附性数据，可以对PrEP试验进行最佳分析。通过提供一个“金标准”工具来监测杀微生物剂的依从性，SMART(R)不仅可以提供一个优越的试验数据集，还可以用来识别与依从性差相关的行为，并制定缓解这些行为的策略。1