Background: Patients with diabetic and idiopathic gastroparesis with delayed gastric emptying and moderate to severe nausea were enrolled into a phase II multicenter, randomized, double-blind, placebo-controlled trial. Subjects were randomized to receive oral 85mg tradipitant bid or placebo (1:1) for 4 weeks. Of the 152 patients, 60% of patients had idiopathic and 40% had diabetic gastroparesis.
Methods: The primary outcome was change in average nausea from baseline, measured using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptoms were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM).
Results: A statistically significant and clinically meaningful improvement in nausea and overall gastroparesis symptoms was observed in patients on tradipitant. Subjects receiving tradipitant had a significant decrease in their average nausea score compared to placebo with LS mean difference (95% CI) of -0.53 (-0.92, -0.13, p=0.0099) as well as a significant increase in nausea free days (28.8% increase on tradipitant compared to 15.0% increase on placebo, p=0.0160). A clinically meaningful response of 1-point or more improvement on the GCSI total score was observed in 46.0% of patients on tradipitant compared to 24.2% of patients on placebo (p=0.0086).
Conclusions: Tradipitant treatment resulted in statistically and clinically meaningful improvements in nausea and overall gastroparesis symptoms. Tradipitant was well tolerated with comparable rates of adverse events between tradipitant and placebo groups. These robust efficacy results suggest tradipitant has the potential to become a first line treatment for idiopathic and diabetic gastroparesis.
J.L. Carlin: Employee; Self; Vanda Pharmaceuticals, Inc. V.R. Lieberman: Employee; Self; Vanda Pharmaceuticals, Inc. Stock/Shareholder; Self; Vanda Pharmaceuticals, Inc. A. Dahal: Employee; Self; Vanda Pharmaceuticals, Inc. Stock/Shareholder; Self; Vanda Pharmaceuticals, Inc. M.S. Keefe: Employee; Self; Vanda Pharmaceuticals. Stock/Shareholder; Self; Vanda Pharmaceuticals. C. Xiao: Employee; Self; Vanda pharmaceutical inc. G. Birznieks: Employee; Self; Vanda Pharmaceuticals. M.H. Polymeropoulos: Employee; Self; Vanda Pharmaceuticals Inc.