S1588 Pooled Efficacy Analysis of Tradipitant in Idiopathic and Diabetic Gastroparesis Study VP-VLY-686-3301 and VP-VLY-686-2301

Introduction: Tradipitant is a novel NK-1 receptor antagonist studied in diabetic and idiopathic gastroparesis for short-term relief of nausea. This report presents the pooled analysis from 2 multicenter, randomized, double-blind, placebo-controlled studies (VP-VLY-686-3301 and VP-VLY-686-2301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis. Methods: N=342 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea were included in the pooled ITT (Intent-to-Treat) population. Subjects were randomized to 85mg tradipitant twice a day (n=175) or placebo (n=167) and endpoints were assessed at Week 4. Nausea was assessed with the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptom improvement was evaluated with the Patient Global Impression of Change (PGI-C) and Overall Patient Benefit (OPB) scales. Sensitivity analyses were performed to control for confounders. Results: In a pooled analysis of double-blind subjects in the ITT population of Study 1 and Study 2, tradipitant demonstrated a clinically meaningful and statistically significant improvement in average nausea at week 4 (-1.15 for tradipitant v. -0.85 for placebo, P=0.0138). Significant improvement was seen in the number of nausea free days (20.96% improvement for tradipitant v. 12.52% for placebo, P=0.0085). Tradipitant also showed improvement in other gastroparesis symptoms as measured by the GCSI total score (-0.99 for tradipitant v. -0.76 for placebo, P=0.0265). Responder rates for PGI-C were 79.3% on tradipitant versus 69% on placebo at week 4 (P value = 0.036). For the Overall Patient Benefit, more patients improved on tradipitant versus placebo with 85.3% v. 71.2% at week 4 (P= 0.002). Sensitivity analysis adjusting for drug compliance confirmed the PK population (tradipitant blood levels ≥ 140ng/mL) in the pooled data set (n=284). In the pooled PK Population, tradipitant significantly improved average nausea at week 4 with -1.38 for tradipitant v. -0.85 for placebo (P=0.0001). Conclusion: Pooling the data provided an opportunity to analyze a much larger data set, increase statistical power, and confirm results and subpopulations from the 2 separate studies. In the pooled analysis, we observed a clinically meaningful and significant effect on change of nausea severity at week 4. Improvements were also seen across core gastroparesis symptoms and overall measures of gastroparesis.