S3123 Exposure-Response Efficacy Analysis of Tradipitant in Idiopathic and Diabetic Gastroparesis

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 85 mg tradipitant twice per day 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 ≤140 ng/ml tradipitant blood concentration at any visit to classify participants in the high (n = 309) and low (n = 218) pharmacokinetics (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 percentage of nausea free days (an addition of 35.6% of days for high PK versus 22.6% for low PK; P = 0.0002). Conclusion: 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.