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Velusetrag accelerates gastric emptying in subjects with gastroparesis: a multicentre, double‐blind, randomised, placebo‐controlled, phase 2 study
Author(s) -
Kuo Braden,
Barnes Chris N.,
Nguyen Deanna D.,
Shaywitz David,
Grimaldi Maria,
Renzulli Cecilia,
Canafax Daniel,
Parkman Henry P.
Publication year - 2021
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.16344
Subject(s) - gastroparesis , medicine , placebo , gastric emptying , gastroenterology , crossover study , adverse effect , stomach , alternative medicine , pathology
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 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).