Nakajima A, et al. - Researchers examined elobixibat regarding its efficacy for short-term treatment of chronic constipation, and safety, patient satisfaction, and quality of life with long-term treatment. Elobixibat treatment was noted resolving constipation in the short-term. Both short-term and long-term treatments were well tolerated. This novel approach is thus supported as a valuable option to increase intracolonic concentrations of endogenous bile acid for the treatment of chronic constipation.

Methods

• In Japan, two phase 3 studies of patients (aged 20–80 years) with at least 6 months of chronic constipation were performed; the patients satisfied Rome III criteria for functional constipation, including fewer than three spontaneous bowel movements per week.
• The first trial was a 2-week, randomised, double-blind, placebo-controlled study; it included patients enrolled at 16 clinics.
• Patients (after a 2-week run-in period) were randomly assigned (1:1) to either elobixibat 10 mg/day for 2 weeks or placebo.
• They performed randomisation without stratification using permuted block method (block size six).
• They achieved masking to treatment allocation with identical appearances of elobixibat and placebo, which were supplied in sealed, opaque containers.
• Patients, investigators and analysts were concealed regarding group assignment.
• The second trial was an open-label, 1-year study; it included patients enrolled at 34 clinics or hospitals.
• All patients received elobixibat; participants could titrate the dose to 5 mg/day or 15 mg/day, or maintain the 10 mg/day dose.
• Participants took the study drug as an oral tablet once per day before breakfast in both studies.
• The change from baseline (ie, last week of the 2-week run-in) in the frequency of spontaneous bowel movements during week 1 of treatment was assessed as the primary outcome of the 2-week randomised trial.
• Safety (type, severity, and incidence of adverse drug reactions) at all times from treatment initiation was assessed as the primary outcome of the 52-week open-label trial.
• They performed all efficacy analyses based on the modified intention-to-treat (ITT) population without imputation for any missing data.
• All patients who received at least one dose of study drug were included in safety analyses.

Results

• In the 2-week randomised trial, 133 patients from Nov 4, 2015 to June 11, 2016 were assigned to treatment: 70 to elobixibat (69 included in the modified ITT and safety populations) and 63 to placebo.
• Researchers noted greater frequency of spontaneous bowel movements per week during week 1 of treatment with elobixibat (least-squares mean 6·4, 95% CI 5·3–7·6) than with placebo (1·7, 1·2–2·2), p<0·0001).
• From Oct 31, 2015 to March 15, 2017, 341 patients were allocated to 52 weeks of elobixibat (340 included in the modified ITT and safety populations).
• An adverse drug reaction was encountered in 163 (48%) patients in the 52-week trial, the most common of which were mild gastrointestinal disorders (in 135 [40%] patients).
• One patient reported inguinal hernia with elobixibat in the 52-week study as a moderate adverse drug reaction.
• In both trials, the most common adverse drug reactions included mild abdominal pain (13 [19%] patients with elobixibat and one [2%] with placebo in the 2-week randomised trial, and 82 [24%] patients in the 52-week trial) and diarrhoea (nine [13%] patients with elobixibat and none with placebo in the 2-week randomised trial and 50 [15%] in the 52-week trial).