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

Abstract

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 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).

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 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.

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