Introduction 

Chronic constipation, the sixth most frequent gastrointestinal complaint, has reported a prevalence of 16%. The use of laxatives and medications that change the function of the intestinal epithelium are associated with abdominal pain, diarrhea, nausea, dehydration and electrolyte abnormalities in short term and increased risk of resistance or habituation and atonic colon in long-term. Elobixibat, a locally acting ileal bile acid transporter inhibitor, accelerates colonic transit. It aids in looser stool consistency, decreased constipation rating and reduced straining compared with placebo and is associated with a significantly greater number of spontaneous bowel movements per week and improved bloating severity.

Aim

To assess efficacy and safety of elobixibat for short-term treatment of chronic constipation in Indian patients

Patient Profile 

Method

Study Design

• Prospective, randomized, multicenter, double‑blind, placebo‑controlled, parallel‑group, phase III study
• Patients were randomized to elobixibat 5 mg or to placebo groups for two weeks

Endpoints

• Primary efficacy endpoint: change in weekly frequency of spontaneous bowel movements (SBMs) at the end of treatment over baseline
• Secondary efficacy endpoints: proportion of patients with complete spontaneous bowel movement (CSBM) “response” (≥3 CSBMs/week and an increase of ≥1 CSBM/week from baseline), proportion of patients with a SBM within 24 hours after the first dose of study drug and median time to first SBM

Results 

Efficacy 

• Elobixibat significantly improved weekly frequency of SBMs as compared to placebo (3.83 vs. 2.68, least square mean difference: 1.15; p = 0.008) at the end of treatment in patients with chronic constipation (Figure 1)
• A significantly greater proportion of patients achieved CSBM “response” with elobixibat versus placebo (49.33% vs. 26.76%, difference 22.57%, p = 0.005)
• A higher proportion of patients in the elobixibat group achieved a SBM within 24 hours after the first dose of study drug versus those in the placebo group (51% vs. 37%)
• The median time to first SBM was shorter with elobixibat as compared to placebo (11 hours and 26 minutes vs. 22 hours and 30 minutes) showing clinically meaningful onset of action with the use of elobixibat

Figure 1: Effect of elobixibat on the primary endpoint in comparison with placebo

Safety   

• Most of the adverse events (AEs) were mild in severity (reported in 95% patients)
• Mild AEs were reported in both study groups (elobixibat 60% vs. placebo 35%) and moderate were reported in only elobixibat as compared to placebo (5% vs. 0)        
• Abdominal pain was the most commonly reported AE (elobixibat 7.89% vs. placebo 4.05%) followed by abdominal distention (elobixibat 3.95% vs. placebo 4.05%) and dry mouth (elobixibat 2.63% vs. placebo 1.35%)
• No deaths or serious AEs occurred
• No clinically significant abnormalities were observed in vital signs, clinical laboratory parameters and physical examination data

Conclusion 

• Elobixibat was well tolerated and effective in improving bowel movement frequency within two weeks of treatment in Indian patients with chronic constipation
• Elobixibat offered the benefits of good tolerability, earlier onset of action, short treatment durations and convenient once-daily dosing in difficult to treat chronic functional constipation

Indian J Gastroenterol. 2025; 44(3): 336-344