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Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions.
J Gastroenterol Hepatol 2018; 33(5):980-989JG

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+Show Affiliations

Chinese PLA General Hospital, Beijing, China.Renji Hospital, Shanghai, China.General Hospital of Shenyang Military Region of Chinese PLA, Shenyang, China.Sir Run Shaw Hospital, Hangzhou, China.Zhongshan Hospital, Shanghai, China.First Affiliated Hospital of Harbin Medical University, Harbin, China.Ruijin Hospital, Shanghai, China.Delta Research Partners, Monroe, Louisiana, USA.Ironwood Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.Ironwood Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.Ironwood Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.Ironwood Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.AstraZeneca AB, Shanghai, China.AstraZeneca AB, Shanghai, China.AstraZeneca AB, Shanghai, China.AstraZeneca AB, Shanghai, China. Duke-NUS Medical School Office of Clinical Sciences, Singapore.

Pub Type(s)

Clinical Trial, Phase III
Journal Article

Language

eng

PubMed ID

29319191

Citation

Yang, Yunsheng, et al. "Linaclotide in Irritable Bowel Syndrome With Constipation: a Phase 3 Randomized Trial in China and Other Regions." Journal of Gastroenterology and Hepatology, vol. 33, no. 5, 2018, pp. 980-989.
Yang Y, Fang J, Guo X, et al. Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions. J Gastroenterol Hepatol. 2018;33(5):980-989.
Yang, Y., Fang, J., Guo, X., Dai, N., Shen, X., Yang, Y., ... Lim, S. (2018). Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions. Journal of Gastroenterology and Hepatology, 33(5), pp. 980-989. doi:10.1111/jgh.14086.
Yang Y, et al. Linaclotide in Irritable Bowel Syndrome With Constipation: a Phase 3 Randomized Trial in China and Other Regions. J Gastroenterol Hepatol. 2018;33(5):980-989. PubMed PMID: 29319191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions. AU - Yang,Yunsheng, AU - Fang,Jingyuan, AU - Guo,Xiaozhong, AU - Dai,Ning, AU - Shen,Xizhong, AU - Yang,Youlin, AU - Sun,Jing, AU - Bhandari,Bal Raj, AU - Reasner,David S, AU - Cronin,Jacquelyn A, AU - Currie,Mark G, AU - Johnston,Jeffrey M, AU - Zeng,Peter, AU - Montreewasuwat,Niwat, AU - Chen,George Zhijian, AU - Lim,Sam, Y1 - 2018/03/12/ PY - 2017/09/11/received PY - 2017/12/22/revised PY - 2018/01/01/accepted PY - 2018/1/11/pubmed PY - 2018/8/11/medline PY - 2018/1/11/entrez KW - abdominal pain KW - constipation KW - guanylate cyclase KW - irritable bowel syndrome SP - 980 EP - 989 JF - Journal of gastroenterology and hepatology JO - J. Gastroenterol. Hepatol. VL - 33 IS - 5 N2 - 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. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/29319191/Linaclotide_in_irritable_bowel_syndrome_with_constipation:_A_Phase_3_randomized_trial_in_China_and_other_regions_ L2 - https://doi.org/10.1111/jgh.14086 DB - PRIME DP - Unbound Medicine ER -