dc.contributor.author | Rao, Satish | |
dc.contributor.author | Shiff, Steven J | |
dc.contributor.author | Lavins, Bernard J | |
dc.contributor.author | Jia, Xinwei D | |
dc.contributor.author | Shi, Kelvin | |
dc.contributor.author | MacDougall, James E | |
dc.contributor.author | Shao, James Z | |
dc.contributor.author | Eng, Paul | |
dc.contributor.author | Fox, Susan M | |
dc.contributor.author | Schneier, Harvey A | |
dc.contributor.author | Kurtz, Caroline B | |
dc.contributor.author | Johnston, Jeffrey M | |
dc.contributor.author | Lembo, Anthony J. | |
dc.contributor.author | Currie, Mark G. | |
dc.date.accessioned | 2013-05-02T14:32:18Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Rao, Satish, Anthony J. Lembo, Steven J. Shiff, Bernard J. Lavins, Mark G. Currie, Xinwei D. Jia, Kelvin Shi, et al. 2012. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. The American Journal of Gastroenterology 107(11): 1714-1724. | en_US |
dc.identifier.issn | 0002-9270 | en_US |
dc.identifier.issn | 1572-0241 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10609764 | |
dc.description.abstract | Objectives: Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C). Methods: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μg oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period. There were four primary end points, the Food and Drug Administration's (FDA's) primary end point for IBS-C (responder: improvement of ≥30% in average daily worst abdominal pain score and increase by ≥1 complete spontaneous bowel movement (CSBM) from baseline (same week) for at least 50% of weeks assessed) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored. Results: The trial evaluated 800 patients (mean age=43.5 years, female=90.5%, white=76.9%). The FDA end point was met by 136/405 linaclotide-treated patients (33.6%), compared with 83/395 placebo-treated patients (21.0%) (P<0.0001) (number needed to treat: 8.0, 95% confidence interval: 5.4, 15.5). A greater percentage of linaclotide patients, compared with placebo patients, reported for at least 6/12 treatment period weeks, a reduction of ≥30% in abdominal pain (50.1 vs. 37.5%, P=0.0003) and an increase of ≥1 CSBM from baseline (48.6 vs. 29.6%, P<0.0001). A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points (P<0.05). Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points (P<0.001). During the RW period, patients remaining on linaclotide showed sustained improvement; patients re-randomized from linaclotide to placebo showed return of symptoms, but without worsening of symptoms relative to baseline. Diarrhea, the most common AE, resulted in discontinuation of 5.7% of linaclotide and 0.3% of placebo patients. Conclusions: Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | doi:10.1038/ajg.2012.255 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504311/pdf/ | en_US |
dash.license | LAA | |
dc.title | A 12-Week, Randomized, Controlled Trial with a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Linaclotide in Irritable Bowel Syndrome with Constipation | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | The American Journal of Gastroenterology | en_US |
dash.depositing.author | Lembo, Anthony J. | |
dc.date.available | 2013-05-02T14:32:18Z | |
dc.identifier.doi | 10.1038/ajg.2012.255 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Lembo, Anthony | |