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: The open label arm of Study 3301 enrolled n=531 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea, and at least 1 vomiting episode. Patients received 85 mg tradipitant twice daily for 12 weeks. Nausea was assessed using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Gastroparesis symptoms were assessed every 2 weeks in clinic using the Gastroparesis Cardinal Symptom Index (GCSI).
An exposure response subgroup analysis was performed to control for low drug exposure. A threshold of ≤140ng/ml tradipitant blood concentration at any visit was used to classify participants in the High (n=309) and Low (n=218) PK Populations. Results were further stratified to compare average nausea severity and gastroparesis symptoms at baseline nausea severity scores of ≥2 and ≥2.5 for Low (n=129 and n=89, respectively) and High (n=170 and n=110, respectively) PK subgroups.
Results: Patients in the High PK subgroup had statistically improved nausea severity at Week 12 compared to the Low PK subgroup (-1.19 vs. -0.78, respectively; p< 0.0001), including at baseline nausea severity scores of ≥2 (-1.61 vs. -0.98, respectively; p< 0.0001) and ≥2.5 (-1.77 vs. -1.03, respectively; p< 0.0001). The High PK subgroup also had statistically significant improvement in nausea-free days at Week 12 compared to Low PK (+35.65% vs. +22.56%, respectively; p=0.0002), including at baseline nausea scores of ≥2 (+36.36% vs. 18.15%, respectively; p=0.0002) and ≥2.5 (+33.44% vs. 14.11%, respectively; p=0.0009).
Discussion: A significant exposure response was seen in both idiopathic and diabetic gastroparesis patients receiving open label tradipitant for 12 weeks. Patients with higher blood levels of tradipitant significantly improved in average nausea severity and in overall gastroparesis symptoms compared to patients with low drug blood levels.
Disclosures:
Jesse Carlin: Vanda Pharmaceuticals, Inc. – 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).
Paula Moszczynski: 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, Stock-publicly held company(excluding mutual/index funds).
Gunther Birznieks: Vanda Pharmaceuticals, Inc. – Employee, Stock-publicly held company(excluding mutual/index funds).
Mihael Polymeropoulos: Vanda Pharmaceuticals, Inc. – Advisory Committee/Board Member, Employee, CEO, Stock-publicly held company(excluding mutual/index funds).
Jesse L.. Carlin, PhD, Christos Polymeropoulos, MD, Michaela Fisher, BS, Paula Moszczynski, MS, Garrett Johannsen, BS, Changfu Xiao, PhD, Gunther Birznieks, MS, Mihael Polymeropoulos, MD, PhD. P5062 - Exposure-Response Analysis of Open Label Tradipitant in Idiopathic and Diabetic Gastroparesis in Study VP-VLY-686-3301, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
