A randomized, double‐blind, placebo‐controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis

Abstract

AbstractBackgroundThis study assessed the efficacy and safety of velusetrag—a 5‐HT4 agonist with pan‐gastrointestinal prokinetic activity—for gastroparesis symptom management and gastric emptying (GE).MethodsIn this multicenter, double‐blind, randomized, placebo‐controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7‐day mean Gastroparesis Cardinal Symptom Index 24‐h composite score (GCSI‐24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs).Key Results232 subjects (183 females; 113 idiopathic gastroparesis) received treatment from February 2015 through June 2017. Least‐squares mean improvement from baseline GCSI‐24H (primary endpoint) at week 4 was −1.5 following velusetrag 5 mg vs −1.1 following placebo (treatment difference, −0.4; 95% confidence interval, −0.75 to −0.03; nominal p = 0.0327; Hochberg‐adjusted p = 0.0980 [not significant]). Symptom improvement from baseline was achieved only with velusetrag 5 mg, which resulted in greater improvement from baseline vs placebo in all gastroparesis core symptoms, especially in subjects with idiopathic gastroparesis. Improvement from baseline GE by GES was greater in subjects receiving velusetrag (all doses) vs placebo; >70% of subjects receiving velusetrag 30 mg had GE normalization at 4 h. Treatment‐emergent AEs were generally mild.Conclusions and InferencesVelusetrag treatment was generally well‐tolerated and associated with improved GE vs placebo in subjects with diabetic or idiopathic gastroparesis; however, only the lowest dose, velusetrag 5 mg, was associated with short‐term improvement in gastroparesis symptoms.ClinicalTrials.govNCT02267525.