Weeks 12, 32.4 vs 13.two , NNT 5.2 (four.0, 7.three) at weeks 16, for at least linaclotide 290 g od (n =401) vs placebo (n =403) for 26 weeks Linaclotide vs placebo (n =802): Treatment-emergent Ae: 56.two (228/406) vs 53.0 (210/396); p =0.39; Diarrhea 19.five vs 3.5 ; p ,0.0001; (discontinued remedy resulting from diarrhea: five.7 vs 0.3 ); Discontinued treatment because of Ae: 5.7 vs 0.three ; SAe: 0.5 (1 asthma, 1 pericardial effusion and pericarditis) vs 0.five (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 56.6 (228/402); p ,0.05; Diarrhea 19.7 vs two.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: 54.8 vs 41.8 ; 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 16.6 ; P , 0.0001 Details reported in Rao 2012 and Chey 2012 (n =1607). Linaclotide vs placebo: overall Ae incidence: 56 vs 53 . Diarrhea: Trial 31: 19.5 vs 3.five ; Trial 302: 19.7 vs two.five (Discontinued treatment resulting from diarrhea five.7 vs 0.3 and four.five vs 0.two , respectively). SAes: ,2 in each groups (none related to diarrhea). According to data from Chey 2012, Rao 2012, but this pooled evaluation reported eMA endpointssecondary endpoints Efficacy (primary endpoints) Adverse events (Ae) noteModified Rome II criteria, 12 weeks from the year with abdominal pain or abdominal discomfort that had two of 3 predefined features, and ,three SBMs per week, 1 further bowel symptom, and NRS three for every day abdominal pain at its worst, with typical ,3 CSBMs per week and #5 SBMs per week in the course of the 14 days 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 of your year with abdominal discomfort or abdominal discomfort that had 2 of three predefined functions, and ,3 SBMs Trial 302, NCTAuthors study designcountry, study periodQuigleyPooled data of two Phase III doubleblind RCTs (Trial 31, NCT00948818 and Trial 302, NCT00938717)Usa and Canada, multicentre, July 2009 eptemberRaoPhase III double-blind RCT118 centers (111 within the United states of america, 7 in Canada) from July 2009 ulyClinical Medicine Insights: Gastroenterology 2013:CheyPhase III double-blind RCT102 centers in the United states, July 2009 eptemberperweek, 1 additional bowel symptom, and NRS 3 for everyday abdominal pain at its worst, with average ,3 CSBMs per week and #5 SBMs per week9/12, at weeks 16, (ii) 30 reduce in typical everyday worst abdominal discomfort 36.Anidulafungin 9 vs 17.Mifanertinib (dimaleate) four , NNT five.PMID:24065671 1 (3.9, 7.4); (iii) three CSBMs and an increase of 1 CSBM,15.7 vs three.5 , NNT 8.two (six.2, 12.1); (iv) combined responder 12.0 vs 2.five , NNT 10.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 Increase in weekly CSBM through the 12-week remedy period from baseline “75 CSBM responder” (a patient for 75 of your treatment weeks, had a weekly CSBM 3 and a rise 1); improved in SBM, Daily.