POTENTIAL EFFECTS OF FOOD ON A NOVEL DRUG DELIVERY SYSTEM (DDS) TO DELIVER A THERAPEUTIC COMPOUND IN THE COLON

Abstract

Abstract The clinical remission rate in moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) has plateaued at ~15-20% despite the approval of multiple therapeutics. Research has shown that an inadequate amount of drug at the disease site in the colon may be responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to autonomously identify colon entry based on gastrointestinal (GI) anatomy, independent of the variable GI physiological conditions, and deliver a bolus of a liquid drug formulation to the colon mucosa to improve efficacy and reduce systemic toxicity. In this study, we aim to evaluate the safety, tolerability, and functionality of the DDS devices in fasted and fed states in normal healthy volunteers (NHV). NHV were enrolled and administered a single DDS device at each week in either the fasted state or in 1 of 3 possible fed schedules over ~ 4 weeks. Subjects were fasted overnight and were dosed in the morning (fasted schedule) or fasted overnight and consumed a light breakfast with equivalent calories and protein/fat content of egg-beater meal either immediately before administration of DDS device (fed schedule #1), 30 minutes post-dose (fed schedule #2), or 2 hours pre-dose (fed schedule #3). Devices were recovered from the feces, and data were extracted from the capsule to confirm the function of the colon entry call and activation of payload release. A total of twelve NHV (N=12) were enrolled in this study. Eleven subjects completed all four fasted/fed dosing schedules over 4 weeks, while one subject was withdrawn due to non-compliance with device recovery. Overall, the DDS device was well-tolerated in all enrolled subjects with a total of 46 devices dosed in this study. Mild AEs were reported as possibly related to the device in two subjects, including vomiting (N=1) and nausea (N=1) following device administration which was resolved on the same day. No other device-related AEs were reported in this study. Out of 44 devices administered to 11 subjects, 43 were successfully recovered, and device data was successfully recovered from 39 devices for device function evaluation. Thirty-nine devices for which data was recovered (100%) had successfully identified colon entry calls (S4) and activated H2 gas cells for delivery in all fasted/fed schedules (Table 1). Thirty-eight (38) out of 39 recovered devices (97.4%) had successfully activated the payload release function, and one did not (Table 1). The results from this study demonstrated that the DDS device was well-tolerated and functioned as intended in NHV subjects in these four fasted/fed dosing schedules and confirmed that the potential food effect of a light breakfast meal on the device function of the DDS device is minimal.