Correspondence to Author: Saroj Kant Sinha¹,Manas Kumar Mondal², D P Yadav³, B Ramesh Kumar⁴, Anumula Kavitha⁵, Piyush Agarwal^6*, Brajesh Kumar Jha⁶, Jaganmohan Somagoni⁶, Sanketh Kumar Chakilam⁶, Pramod Kumar Potluri⁶. 

1. Post Graduate Institute of Medical Education and Research (PGIEMR), Chandigarh, India
2. Department of Gastroenterology, Nil Ratan Sirkar Medical College and Hospital, Kolkata, India
3. Institute of Medical Sciences, Banaras Hindu University (BHU), Varanasi, India.
4. Osmania General Hospital, Department of Gastroenterology, Hyderabad, India
5. Government General Hospital, Department of Gastroenterology, Guntur, India.
6. Global Clinical Management, Dr. Reddy’s Laboratories Ltd, Hyderabad, India

DOI: 10.52338/jjogastro.2025.4979

Abstract:

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%)].
Conclusion: Linaclotide was well tolerated and improved bowel movement within twelve weeks of treatment in Indian patients with chronic constipation.

Keywords: Linaclotide, Defecation, Guanylate cyclase C receptor, Constipation, Intention to treat analysis

Citation:

Piyush Agarwal, Efficacy and Safety of Linaclotide in Indian Patients with Chronic Constipation- A Randomized, Multicentre, Double Blind, Placebo Controlled, Parallel-Group Study. Japanese Journal of Gastroenterology 2025.