Elobixibat, a minimally absorbed inhibitor of ileal bile acid transporter (IBAT), is safe and effective for treating chronic constipation, according to results from a phase 3 trial.
"This new medication actually enhances a natural laxative that we all have in our gastrointestinal tract," Dr. Michael Camilleri of the Mayo Clinic in Rochester, Minnesota, the study's senior author, told Reuters Health by phone.
While only a minority of cases of functional constipation can be traced to a deficiency in bile acid, he added, "I think we can generalize that this medication would work for all comers with constipation, not just the ones that have a deficiency."
Bile acids help relieve constipation by inducing water secretion and speeding colonic transit, and elobixibat is believed to target both mechanisms, Dr. Camilleri and his colleagues note in The Lancet Gastroenterology & Hepatology, online May 24.
They randomly assigned 133 patients to receive 10 mg of elobixibat or placebo for two weeks, after a two-week flush-out period. They also conducted an open-label study in 341 patients, who took 5 to 15 mg of elobixibat a day for 52 weeks.
In the short-term study, patients on elobixibat had a mean 6.4 bowel movements during the first week of treatment, versus 1.7 for the placebo group. Nearly half of the patients in the open-label trial had adverse drug reactions, most frequently mild gastrointestinal issues.
In both studies, mild abdominal pain and diarrhea were the most commonly reported adverse drug reactions. One patient on elobixibat developed an inguinal hernia, which was considered to be a moderate adverse drug reaction.
EA Pharma and Mochida Pharmaceutical Co., both based in Tokyo, funded the research and are marketing elobixibat in Japan and other Asian countries. Employees of EA Pharma and Albireo AB (Gothenburg, Sweden) helped conduct the research.
While a large phase 2b trial of elobixibat was conducted in the U.S., Dr. Camilleri noted, phase 3 trials have not been done in the U.S. or Europe. "I do anticipate that at some point in time, this compound or something very similar to it will progress to the clinical trials that are needed for approval in the U.S. and Europe," he said.
About half of patients with chronic constipation are not satisfied with available treatments, Dr. Satish Rao of the Medical College of Georgia in Augusta notes in an accompanying editorial. "Elobixibat, through its unique mechanism of action, opens the door for another novel approach to treating chronic constipation."
While the results are "promising," Dr. Rao adds, he calls for them to be confirmed in "more rigorous, long-term, phase 3, placebo-controlled trials of at least 3-6 months' duration, using more robust primary efficacy endpoints."