For 26 weeks Linaclotide vs placebo (n =802): Treatment-emergent Ae: 56.2 (228/406) vs 53.0 (210/396); p =0.39; Diarrhea 19.five vs 3.5 ; p ,0.0001; (discontinued remedy resulting from diarrhea: 5.7 vs 0.three ); Discontinued treatment due to Ae: 5.7 vs 0.3 ; SAe: 0.5 (1 asthma, 1 pericardial effusion and pericarditis) vs 0.5 (1 chronic cholecystitis, 1 duodenitis, gastroenteritis, hiatal hernia, esophagitis, renal cyst, and urinary tract infection) Linaclotide vs placebo (n =805): Treatment-emergent Ae: 65.4 (263/03) vs 56.six (228/402); p ,0.05; Diarrhea 19.7 vs 2.5 ; p ,0.0001 (discontinued Trial 31, NCT00948818 (i) 26-week abdominal pain/discomfort responders and 26-week IBS degreeof-relief responders (responders for 13 out of 26 weeks therapy); (ii) the IBS-QoL and eQ-5D instruments; (iii) Other symptoms tool frequency, stool consistency, severity of straining and abdominal bloating (i) 12-week abdominal pain/discomfort responders: linaclotide vs placebo, Trial 31: 54.Furo[3,2-c]pyridine custom synthesis 8 vs 41.eight ; Trial 302: 54.1 vs 38.five ; P , 0.001 (ii) 12-week IBS degree-of-relief responders, Trial 31: 37.0 vs 18.5 ; Trial 302: 39.four vs 16.six ; P , 0.0001 Specifics reported in Rao 2012 and Chey 2012 (n =1607). Linaclotide vs placebo: all round Ae incidence: 56 vs 53 . Diarrhea: Trial 31: 19.5 vs 3.5 ; Trial 302: 19.7 vs two.5 (Discontinued therapy as a consequence of diarrhea 5.7 vs 0.3 and four.5 vs 0.two , respectively). SAes: ,2 in each groups (none related to diarrhea). Depending on data from Chey 2012, Rao 2012, but this pooled analysis reported eMA endpointssecondary endpoints Efficacy (primary endpoints) Adverse events (Ae) noteModified Rome II criteria, 12 weeks with the year with abdominal pain or abdominal discomfort that had two of three predefined options, and ,three SBMs per week, 1 added bowel symptom, and NRS 3 for daily abdominal discomfort at its worst, with typical ,3 CSBMs per week and #5 SBMs per week during the 14 days just before randomization linaclotide 290 g od (n =405) vs placebo (n =395) for 12 weeks; followed by a 4-week randomized withdrawal (Rw) period Modified Rome II criteria, 12 weeks in the year with abdominal pain or abdominal discomfort that had 2 of 3 predefined attributes, and ,three SBMs Trial 302, NCTAuthors study designcountry, study periodQuigleyPooled information of two Phase III doubleblind RCTs (Trial 31, NCT00948818 and Trial 302, NCT00938717)United states of america and Canada, multicentre, July 2009 eptemberRaoPhase III double-blind RCT118 centers (111 within the Usa, 7 in Canada) from July 2009 ulyClinical Medicine Insights: Gastroenterology 2013:CheyPhase III double-blind RCT102 centers inside the Usa, July 2009 eptemberperweek, 1 extra bowel symptom, and NRS 3 for daily abdominal pain at its worst, with typical ,3 CSBMs per week and #5 SBMs per week9/12, at weeks 1?six, (ii) 30 lower in average daily worst abdominal discomfort 36.(R)-(Tetrahydrofuran-2-yl)methanol site 9 vs 17.PMID:24605203 4 , NNT 5.1 (three.9, 7.4); (iii) three CSBMs and an increase of 1 CSBM,15.7 vs 3.five , NNT eight.two (six.two, 12.1); (iv) combined responder 12.0 vs 2.five , NNT ten.five (7.7, 16.8), P , 0.0001 in all evaluation linaclotide 75 g (n =79), 150 g (n =82), 300 g (n =84) or 600 g (n =89) od vs placebo (n =85) for 12 weeks Enhance in weekly CSBM during the 12-week therapy period from baseline “75 CSBM responder” (a patient for 75 on the remedy weeks, had a weekly CSBM three and an increase 1); improved in SBM, Daily bowel movement and abdominal symptoms assessment; weekly assessments of sufficient relief of IBS symptoms, worldwide relief o.