Velusetrag

This 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).

In 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).

232 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.

Velusetrag 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.

NCT02267525.

Bisacodyl is a member of the diphenylmethane family and is considered to be a stimulant laxative. It has a dual prokinetic and secretory action and needs to be converted into the active metabolite bis‐(p‐hydroxyphenyl)‐pyridyl‐2‐methane (BHPM) in the gut to achieve the desired laxative effect. Bisacodyl acts locally in the large bowel by directly enhancing the motility, reducing transit time, and increasing the water content of the stool. A recent network meta‐analysis concluded that bisacodyl showed similar efficacy to prucalopride, lubiprostone, linaclotide, tegaserod, velusetrag, elobixibat, and sodium picosulfate for the primary endpoint of ≥3 complete spontaneous bowel movements (CSBM)/week and an increase of ≥1 CSBM/week over baseline. The meta‐analysis also found that bisacodyl may be superior to the other laxatives for the secondary endpoint of change from baseline in the number of spontaneous bowel movements per week in patients with chronic constipation. This observation stimulated the authors to review the available literature on bisacodyl, which has been available on the market since the 1950 s.

The aim of the current review was to provide an overview of the historic background, structure, function, and mechanism of action of bisacodyl. Additionally, we discuss the important features and studies for bisacodyl to understand its peculiar characteristics and guide its use in clinical practice, but also stimulate research on open questions.