Jesse L. Carlin, PhD, Christos Polymeropoulos, MD, Michaela Fisher, BS, Garrett Johannsen, BS, Changfu Xiao, PhD, Gunther Birznieks, MS, Mihael H. Polymeropoulos, MD, PhD Vanda Pharmaceuticals, Inc., Washington, DC Introduction: Tradipitant is a novel NK1R antagonist studied in diabetic and idiopathic gastroparesis. This report presents the analysis from the open-label arm of a multicenter, randomized, double-blind, placebo-controlled study (VP-VLY-686-3301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis. Methods: N=531 idiopathic and diabetic gastroparesis patients with delayed gastric emptying received open label 85mg tradipitant BID for 12 Weeks. Nausea was assessed using the 5-point Gastroparesis Core Symptom Daily Diary. Gastroparesis symptoms were assessed every 2 weeks in clinic using the Gastroparesis Cardinal Symptom Index (GCSI). An exposure response analysis was performed to control for low drug exposure. We used a threshold of ≤140ng/ml tradipitant blood concentration at any visit to classify participants in the High (n=309) and Low (n=218) PK Populations. Results: Patients improved the average nausea score significantly from baseline after 12 weeks tradipitant (improvement of -1.01 vs 2.14 at baseline, p< 0.0001). A significant improvement was also seen in the percent of nausea free days (an addition of 51.76% of days for tradipitant vs. 19.62% at baseline, p< 0.0001). Improvement was also seen in total score for GCSI after 12 weeks (1.50 vs 2.81 at baseline, p< 0.0001).
Patients in the High PK group significantly improved average nausea score compared to the Low PK group at Week 12 (improvement of -1.19 vs -0.78, p< 0.0001). A significant improvement was also seen in the percent of nausea free days (an addition of 35.6% of days for High PK versus 22.6% for Low PK, p=0.0002). Discussion: Tradipitant demonstrated statistically significant improvement from baseline in average nausea severity and percentage of nausea-free days in this 12 week open label study in both idiopathic and diabetic gastroparesis subjects. Additionally, a strong exposure response in nausea improvement was observed when comparing subjects with high drug exposure vs low drug exposure.
Disclosures: Jesse L. Carlin: Vanda Pharmaceuticals – Employee, Stock-publicly held company(excluding mutual/index funds). Christos Polymeropoulos: Vanda Pharmaceuticals, Inc. – Employee, Stock-publicly held company(excluding mutual/index funds). Michaela Fisher: Vanda Pharmaceuticals, Inc. – Employee, Stock-publicly held company(excluding mutual/index funds). Garrett Johannsen: Vanda Pharmaceuticals, Inc. – Employee, Stock-publicly held company(excluding mutual/index funds). Changfu Xiao: Vanda pharmaceuticals inc. – Employee. Gunther Birznieks: Vanda Pharmaceuticals, Inc. – Employee, Stock-publicly held company(excluding mutual/index funds). Mihael H. Polymeropoulos: Vanda Pharmaceuticals, Inc. – President and CEO.
Jesse L. Carlin, PhD, Christos Polymeropoulos, MD, Michaela Fisher, BS, Garrett Johannsen, BS, Changfu Xiao, PhD, Gunther Birznieks, MS, Mihael H. Polymeropoulos, MD, PhD. P2045 - Exposure-Response Efficacy Analysis of Tradipitant in Idiopathic and Diabetic Gastroparesis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
