YKP10811, a novel selective agonist of the serotonin 5-hydroxytryptamine-4 receptor, was superior to placebo in accelerating GI and colonic transit and improving bowel function in patients with functional constipation, according to recent study data.
The mechanism of action of YKP10811 (SK Biopharmaceuticals) “appears to be related to stimulation of intestinal and colonic motility,” Michael Camilleri, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, told Healio Gastroenterology. “Incidentally, it also accelerated gastric emptying of solid food in the same patients. Approval after pivotal trials would add to the therapeutic strategies to treat patients with chronic functional constipation, particularly those who do not respond to first line therapies or the more severely affected patients, such as those with slow transit constipation.”
Camilleri and colleagues performed a phase 2 study in which they randomly assigned patients with functional constipation (mean age, 42.8 years) to receive once-daily placebo (n = 11) or 10 mg (n = 15), 20 mg (n = 16) or 30 mg (n = 15) YKP10811 for 8 days. Patients kept a bowel function diary based on the Bristol Stool Form Scale throughout the study period and underwent scintigraphic assessment of gastric, small-bowel and colonic transit of solids from days 7 to 9.
YKP10811 was associated with acceleration in colon filling at 6 hours (P < .05) and accelerated gastric emptying of ascending colon emptying (P = .016) and colonic transit at 24 (P < .01) and 48 hours (P = .019). There also was increased stool consistency during the study period. The 10-mg and 20-mg doses were most effective overall in accelerating colonic transit, and no serious adverse events occurred.
“YKP10811 accelerated transit at all levels in the gastrointestinal tract and improved bowel functions in patients with functional constipation,” the researchers wrote. “Thus, YKP10811 is likely to be of benefit to patients with functional constipation without rectal evacuation disorders.”
“Recently approved drugs for constipation in the United States have been secretagogues, such as lubiprostone and linaclotide,” Camilleri said. “Prucalopride, another selective 5-HT4 receptor agonist, is approved in many countries but not yet in the United States. There is currently no approved 5-HT4 receptor agonist for constipation, after the withdrawal of tegaserod, which was less selective than the newer generation of 5-HT4 receptor agonists.” – by Adam Leitenberger
Disclosure: The researchers report no relevant financial disclosures.