S1061 A Scintigraphic Study to Evaluate the Localization and Delivery Function of a Drug Delivery System (DDS) Device in Patients With Active Ulcerative Colitis (UC) in a Fasted State

Abstract

Introduction: The clinical remission in moderate to severe ulcerative colitis (UC) and Crohn’s has plateaued at ∼15-20% even with the approval of multiple biologics/drugs. Altas study clearly demonstrated that the lack of adequate amount of drug at the diseased site is responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to identify colon entry based on the gastrointestinal (GI) anatomy and deliver a bolus dose of a therapeutic compound to the colon mucosa to improve efficacy and reduce systemic toxicity. DDS was shown to be well-tolerated and functioned as intended in identifying and releasing radiotracer in the colon of normal healthy volunteers (NHV). Here, we aim to evaluate the safety and functionality of DDS in active UC patients in a fasted state. Methods: Patients with endoscopy and histology confirmed UC and active UC status defined as having Mayo score ≥ 2 or elevated Fecal Calprotectin Protein or high sensitivity C-reactive protein within one month of the screening visit were eligible for the study. Each patient was fasted overnight and dosed with a single DDS capsule prior to resuming a normal diet. Each capsule was filled with radioactive marker 111In-DTPA to independently identify DDS localization and to visualize payload release; water radiolabeled with 99mTc-DTPA was co-administered with the DDS to delineate GI landmarks by gamma scintigraphy. The GI transit of DDS and delivery location of the radiotracer were confirmed by serial gamma scintigraphy imaging. Results: This is a preliminary analysis of an ongoing study of active UC patients with Mayo scores between 3-8 enrolled and dosed in the study. GI transit metrics of DDS were consistent with the variable GI motility and the frequent bowel movements observed among active UC patients. DDS device demonstrated correct localization identification of colon entry and release of radiotracer in the colon regardless of variable GI motility, the level of inflammation, or blood in the colon of UC patients compared to NHV (Table), confirmed by gamma scintigraphy image analysis. The dispersion of the radiotracer adequately covered the colon from the site of release throughout the remainder of the colon. Conclusion: This result demonstrated that DDS functioned as intended in identifying and releasing the payload in the colon regardless of GI motility or disease status. Table 1. - GI transits, Residence Time, and Radiotracer (111In-DTPA) Delivery Location of DDS Device post-dose in Active UC patients (PM-602) and Normal Healthy Volunteers (NHV) (PM-601) Subject Mayo score Gastric emptying time (min) Small intestine Residence time (min) Arrival Time at Cecum (min) 1st Capsule release In-111 (min) Capsule location at the time of 1st capsule release Capsule Recovery Time (hrs) No. of Bowel Movements required to recover Capsule 602-116-001 6 104 169 273 324 Cecum 47.67 3 602-116-002 3 23 122 145 190 Cecum 26.50 3 602-116-003 8 38 292 330 354 Cecum 32.83 5 601-NHV (N = 11)* Median N/A 29 228 270 368 Cecum/Asc Colon/Splenic Flexure 23.99 1 (n=6)2 (n=4)3 (n=1) *Excluded one subject due to anomalous transit of the DDS device from the stomach to the duodenum and then back into the stomach.