XHALE, INC. — Department of Health and Human Services SBIR Phase I: 105

Description

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 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 butanone that quickly appears in breath As the subject provides a breath sample by andquot blowingandquot 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 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 months Aim 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 months Aim Optimize the SMART R device for microbicide applications Time 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 andquot gold standardandquot 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 PUBLIC HEALTH RELEVANCE In HIV pre exposure prophylaxis trials such as VOICE sub optimal oral and vaginal product adherence has precluded accurate estimation of drug efficacy We propose to rapidly develop an alternative breath based adherence monitoring tool for clinical investigators studying vaginal and rectal routes of drug microbicide Measurement of microbicide adherence using exhaled breath would allow optimal analysis of pre exposure prophylaxis trials and other clinical trials using vaginal and rectal gels