Velusetrag accelerates gastric emptying in subjects with gastroparesis: a multicentre, double-blind, randomised,...

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.

To assess the efficacy and safety of velusetrag for accelerating GE in subjects with diabetic or idiopathic gastroparesis.

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 t_1/2 ) from each treatment period baseline on day 7. Absolute and percent changes from baseline GE t_1/2 were also assessed. GE was measured using a [¹³ C]-octanoate breath test. Safety was evaluated from treatment-emergent adverse events (TEAEs).

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 t_1/2 compared with placebo (52% vs 5%, P = 0.002), and GE t_1/2 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.

Velusetrag accelerates GE in subjects with diabetic or idiopathic gastroparesis and is generally well tolerated in this population (Clinicaltrials.gov NCT01718938).