Clinical—Alimentary TractLinaclotide Improves Abdominal Pain and Bowel Habits in a Phase IIb Study of Patients With Irritable Bowel Syndrome With Constipation
Section snippets
Study Design
A randomized, double-blind, parallel-group, placebo-controlled, phase IIb study was conducted at 92 clinical centers in the United States and Canada between March 2007 (first patient randomized) and February 2008 (last patient completed). The study was performed in accordance with the Declaration of Helsinki and US21 Code of Federal Regulations and registered on clinicaltrials.gov (NCT00460811). Written informed consent was obtained from each patient prior to participation in the study. The
Patient Disposition, Demographics, and Baseline Characteristics
Nine hundred ninety-six (996) patients signed consent forms, of whom 254 were screen failures and 322 were pretreatment failures. Four hundred twenty patients were randomized to 1 of the 5 treatment arms of the study and received study medication (safety population, N = 420). All but 1 of these patients had at least 1 assessment of the primary efficacy end point (intent-to-treat population, n = 419). A total of 83 (19.8%) patients did not complete the study: 25 (6.0%) because of AEs, 4 (1.0%)
Discussion
The results of this large, 12-week, placebo-controlled trial show that across a wide range of doses linaclotide statistically significantly improved multiple symptoms of IBS-C, including abdominal pain, bloating, and constipation. Linaclotide also resulted in statistically significant improvements in several global measurements. Linaclotide's effects occurred within the first week of therapy and were sustained for the entire 3-month duration of this study. Thus, linaclotide resulted in
Acknowledgments
The authors thank the investigators for their participation in this study and Nicole LaVallee, PhD, who independently reviewed the data set and confirmed the analyses.
Clinicaltrials.gov ID: NCT00460811.
The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by Nicole LaVallee, PhD, a biostatistician
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Cited by (202)
Placebo Response Rates in Trials of Licensed Drugs for Irritable Bowel Syndrome With Constipation or Diarrhea: Meta-analysis
2022, Clinical Gastroenterology and HepatologyCitation Excerpt :Of these, 15 articles reported on 17 RCTs of licensed drugs versus placebo in IBS-C,15–18,20,21,26–34 and 15 articles reported on 17 trials in IBS-D.19,22,23,35–46 The 17 trials in IBS-C contained 4603 patients assigned to placebo. There were 2 RCTs of lubiprostone in IBS-C reported in 1 article,18 6 trials of linaclotide,15,21,26–29 three RCTs of plecanatide reported in 2 articles,17,30 three RCTs of tenapanor,16,20,31 and 3 trials of tegaserod.32–34 The 17 trials in IBS-D contained 3908 patients randomized to placebo.
Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain
2022, Trends in Pharmacological SciencesFocus on Pharmacotherapy for Irritable Bowel Syndrome with Constipation
2021, Gastroenterology Clinics of North America
Conflicts of interest The authors disclose the following: Jeffrey Johnston, Caroline Kurtz, James MacDougall, B. J. Lavins, Mark Currie, Donald Fitch, Chris O'Dea, and Mollie Baird are employees of Ironwood Pharmaceuticals. Anthony Lembo is a paid consultant to Ironwood Pharmaceuticals.
Funding Supported by Ironwood Pharmaceuticals.