Ely’ relieved for 6 weeks FDA end point responder: 30 improvement in average every day worst NRS and enhance 1 CSBM from Activin A Protein site baseline in the identical week for at least 9 in the 12 weeks (i) 30 lower in abdominal discomfort, (ii) 3 CSBMs and an increase of 1 CSBM from baseline, and (iii) combined responder: a patient who met criteria for each i and ii in the identical week. 12-week modify from baseline in abdominal pain, abdominal discomfort, abdominal bloating, stool frequency (CSBM and SBM weekly prices), stool consistency (BSFS), and severity of straining; abdominal pain and CSBM responders; 12-week change from baseline in abdominal fullness and abdominal cramping, IBS symptom severity, constipation severity, adequate relief of IBS-C symptoms, degree of relief of IBS symptoms, and Apolipoprotein E/APOE Protein Biological Activity treatment satisfaction. Adverse events have been monitored Similar as Rao 2012 Similar as Rao 2012 (i) FDA endpoint: linaclotide vs placebo: 33.six vs 21.0 , OR 1.9 (1.four, two.7), P ,0.0001, NNT 8.0 (5.4, 15.5); for at the very least 9/12 (ii) 30 lower in worst abdominal discomfort 34.3 vs 27.1 , OR 1.4 (1.0, 1.9), P=0.03, NNT 13.8 (7.4, 116.1); (iii) 3 CSBMs and an increase of 1 CSBM 19.5 vs 6.three , OR 3.7 (two.three, 5.9), P ,0.0001, NNT 7.6 (five.6, 11.six); (iv) combined responder 12.1 vs 5.1 , OR two.six (1.5, four.5), P=0.0004, NNT 14.2 (9.2, 31.3) (i) FDA endpoint: linaclotide vs placebo: 33.7 vs 13.9 , NNT five.1 (3.9, 7.1) at weeks 1?2, 32.four vs 13.2 , NNT five.2 (4.0, 7.3) at weeks 1?6, for at the least linaclotide 290 g od (n =401) vs placebo (n =403) for 26 weeks Linaclotide vs placebo (n =802): Treatment-emergent Ae: 56.2 (228/406) vs 53.0 (210/396); p =0.39; Diarrhea 19.5 vs three.five ; p ,0.0001; (discontinued treatment as a result of diarrhea: five.7 vs 0.three ); Discontinued remedy because of 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 56.6 (228/402); p ,0.05; Diarrhea 19.7 vs 2.five ; 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 treatment); (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 38.5 ; P , 0.001 (ii) 12-week IBS degree-of-relief responders, Trial 31: 37.0 vs 18.5 ; Trial 302: 39.4 vs 16.six ; P , 0.0001 Details reported in Rao 2012 and Chey 2012 (n =1607). Linaclotide vs placebo: all round Ae incidence: 56 vs 53 . Diarrhea: Trial 31: 19.five vs 3.5 ; Trial 302: 19.7 vs two.5 (Discontinued treatment as a result of diarrhea five.7 vs 0.3 and 4.5 vs 0.2 , respectively). SAes: ,two in each groups (none connected to diarrhea). Depending on information from Chey 2012, Rao 2012, but this pooled analysis reported eMA endpointssecondary endpoints Efficacy (key endpoints) Adverse events (Ae) noteModified Rome II criteria, 12 weeks from the year with abdominal discomfort or abdominal discomfort that had 2 of 3 predefined features, and ,3 SBMs per week, 1 further bowel symptom, and NRS three for everyday abdominal discomfort at its worst, with typical ,three CSBMs per week and #5 SBMs per week during the 14 days prior to randomization linaclotide 290 g od (n =405) vs placebo (n =395) f.
