Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub‐cohort analysis of a phase III, randomized, double‐blind, placebo‐controlled trial

OBJECTIVE: To conduct a sub‐cohort analysis to evaluate the efficacy and safety of linaclotide in Chinese patients with constipation‐predominant irritable bowel syndrome (IBS‐C) using data from a completed trial (NCT01880424). METHODS: In this phase III, double‐blind, placebo‐controlled trial, IBS‐C patients were randomized to receive linaclotide (290 μg/d) or placebo for 12 weeks. Efficacy was assessed with two co‐primary responder end‐points (12‐wk abdominal pain/discomfort: ≥30% reduction in either score with neither deteriorating from baseline for ≥6 wks; 12‐wk IBS degree of relief: score ≤2 for ≥ 6 wks), seven secondary endpoints and several additional end‐points. RESULTS: In total, 659 Chinese IBS‐C patients received linaclotide (n = 327) or placebo (n = 332). The 12‐week abdominal pain/discomfort end‐point was met in 62.1% and 53.3% of the linaclotide‐treated and placebo‐treated patients, respectively (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.05‐1.96, P = 0.023); the 12‐week IBS degree of relief end‐point was achieved in 32.7% and 16.9% of the patients treated with linaclotide and placebo, respectively (OR 2.40, 95% CI 1.66‐3.47, P < 0.001). The linaclotide‐treated patients had a shorter time to the first spontaneous bowel movement than the placebo‐treated patients (23.6 h vs 43.7 h, P < 0.001). Linaclotide produced significantly greater improvement than placebo in all secondary end‐points from the first 2 weeks (all P < 0.001). Diarrhea was reported in 8.3% of linaclotide‐treated patients and 1.2% of placebo‐treated patients. CONCLUSION: Linaclotide (290 μg/d) was efficacious and well‐tolerated in Chinese IBS‐C patients with a rapid onset of effect.