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.