Efficacy and Safety of Linaclotide in Indian Patients with Chronic Constipation- A Randomized, Multicentre, Double Blind, Placebo Controlled, Parallel-Group Study

Background: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor, that causes secretion of chloride and bicarbonate into the intestinal lumen, increasing luminal fluid secretion and accelerating intestinal transit. In this study, we aimed to determine the efficacy and safety of Linaclotide over 12-weeks treatment for chronic constipation in Indian patients. Methods: The current study was a randomized, double-blind, parallel-group, placebo-controlled phase III trial aimed at assessing the efficacy and safety of Linaclotide (72 mcg/145 mcg) in Indian patients with chronic constipation over a treatment duration of 12 weeks. The study intended to include patients who had chronic constipation lasting at least 6 months and met the Rome IV criteria for functional constipation. The efficacy endpoints for this trial were proportion of patients with complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) overall response. Results: Between April, 2023, and June, 2024, 316 patients were randomized into the 12-week trial. In mITT population [N=283 (Linaclotide=142 and placebo=141)], the responder proportions for CSBM and SBM between Linaclotide and placebo demonstrated significant statistical differences of 9.08% (95% CI: 0.79%, 17.37%) and 20.79% (95% CI: 9.54%, 32.04%), respectively. The most common adverse event (AE) was abdominal pain [Linaclotide=5 patients (3.2%) vs placebo=8 patients (5.1%)]. Conclusions: Linaclotide was well tolerated and improved bowel movement within twelve weeks of treatment in Indian patients with chronic constipation.