Velusetrag accelerates gastric emptying in subjects with gastroparesis: a multicentre, double‐blind, randomised, placebo‐controlled, phase 2 study

Summary Background Gastroparesis is a serious gastrointestinal (GI) condition characterised by delayed gastric emptying (GE). Velusetrag—a potent, selective, pan‐gastrointestinal 5‐hydroxytryptamine type 4 receptor agonist—is under investigation for treatment of GI motility disorders including gastroparesis. Aims To assess the efficacy and safety of velusetrag for accelerating GE in subjects with diabetic or idiopathic gastroparesis. Methods In this multicentre, randomised, double‐blind, placebo‐controlled, three‐period fixed‐sequence crossover phase 2 study, subjects with diabetic or idiopathic gastroparesis received oral velusetrag (5, 15 or 30 mg) or placebo once daily for 7 days each. The primary outcome was proportion of subjects achieving ≥20% reduction in GE half‐time (GE t1/2) from each treatment period baseline on day 7. Absolute and percent changes from baseline GE t1/2 were also assessed. GE was measured using a [13C]‐octanoate breath test. Safety was evaluated from treatment‐emergent adverse events (TEAEs). Results Thirty‐four subjects (67.6% female; mean age, 46.3 years; 52.9% with diabetic gastroparesis) were included. Treatment with velusetrag 30 mg significantly increased the proportion of subjects with ≥20% reduction from baseline GE t1/2 compared with placebo (52% vs 5%, P = 0.002), and GE t1/2 was numerically reduced following all three doses of velusetrag relative to placebo treatment. Efficacy was similar between subjects with diabetic and idiopathic gastroparesis. Velusetrag treatment was generally well tolerated; most TEAEs were mild and related to GI transit acceleration. Conclusions Velusetrag accelerates GE in subjects with diabetic or idiopathic gastroparesis and is generally well tolerated in this population (Clinicaltrials.gov NCT01718938). The proportion of subjects with a ≥20% decrease in gastric emptying half‐time from baseline was significantly greater following velusetrag 30 mg compared with placebo in the intent‐to‐treat population after 7 days of treatment (52% vs 5%, adjusted P = 0.002).