Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions.

Abstract

BACKGROUND AND AIM:

Linaclotide is a guanylate cyclase-C agonist approved in multiple countries to treat irritable bowel syndrome with constipation (IBS-C). China has unmet need for well-tolerated therapy that is effective in treating both bowel and abdominal symptoms of IBS-C. This trial evaluated linaclotide's efficacy and safety in IBS-C patients in China and other regions.

METHODS:

This Phase 3, double-blind trial randomized IBS-C patients to once-daily oral 290-μg linaclotide or placebo at centers in China, North America, and Oceania. Patients reported bowel and abdominal symptoms daily; adverse events were monitored. Co-primary and secondary endpoints were tested using a predefined three-step serial gatekeeping multiple comparisons procedure.

RESULTS:

The intent-to-treat population included 839 patients (mean age = 41 years; 82% female; 81% Asian). The trial met all co-primary and secondary endpoints. Co-primary responder criteria were met by 60.0% of linaclotide patients versus 48.8% of placebo patients for abdominal pain/discomfort (≥ 30% decrease for ≥ 6/12 weeks; P < 0.05), and 31.7% of linaclotide versus 15.4% of placebo patients for IBS degree of relief (score ≤ 2 for ≥ 6/12 weeks; P < 0.0001). Secondary 12-week change-from-baseline endpoints (spontaneous bowel movement/complete spontaneous bowel movement frequency, stool consistency, straining, abdominal pain, abdominal discomfort, and abdominal bloating) were significantly improved with linaclotide versus placebo (all P < 0.0001). Diarrhea was the most common adverse event (9.4% linaclotide, 1.2% placebo). Discontinuation rates due to diarrhea were low (0.7% linaclotide, 0.2% placebo).

CONCLUSIONS:

Once-daily 290-μg linaclotide improved bowel habits, abdominal symptoms, and global measures in a predominantly Chinese IBS-C population.

• Authors: Yunsheng Yang, Jingyuan Fang, Xiaozhong Guo, Ning Dai, Xizhong Shen, Youlin Yang, Jing Sun, Bal Raj Bhandari, David S Reasner, Jacquelyn A Cronin, Mark G Currie, Jeffrey M Johnston, Peter Zeng, Niwat Montreewasuwat, George Zhijian Chen, Sam Lim
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 33 Issue 5 Pg. 980-989 (May 2018) ISSN: 1440-1746 [Electronic] Australia
• PMID: 29319191 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Guanylyl Cyclase C Agonists
• Peptides
• linaclotide

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Constipation (drug therapy, etiology)
• Diarrhea (chemically induced)
• Double-Blind Method
• Female
• Guanylyl Cyclase C Agonists (administration & dosage, adverse effects)
• Humans
• Irritable Bowel Syndrome (complications, drug therapy)
• Male
• Middle Aged
• Peptides (administration & dosage, adverse effects)
• Treatment Outcome
• Young Adult