Daily IVRS measurements included worst abdominal pain (WAP), stool consistency, bowel frequency, rectal urgency, and frequency of stool incontinence. Weekly measurement included the IBS Global Symptom score on a 0−4 scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), where patients were asked “How would you rate your IBS symptoms overall over the past 7 days?” During monthly clinic visits, patients completed patient-reported outcomes questionnaires, including the IBS-Symptom Severity Score (IBS-SSS; scaled 0−500

with higher scores indicating more severe symptoms), IBS-quality of life (IBS-QOL; scaled 0−100 with higher scores indicating better quality of life), and EuroQoL-5 Dimension (EQ-5D; scaled 0−1 with lower scores indicating better quality of life) Selleckchem VX-809 and answered the question “Over the past week have you had adequate relief of your IBS symptoms?” Safety assessments included capture of adverse events, clinical laboratory results, 12-lead electrocardiograms, vital signs, and physical examinations. As an additional safety precaution, IVRS-generated notifications were sent to investigators to discontinue patients from the study for click here IVRS-confirmed constipation if the patients’ diary

entries indicated a lack of a bowel movement on 4 consecutive days on more than one occasion or the lack of a bowel movement on any 7 consecutive days (irrespective of whether an adverse event of constipation was reported). Additionally, the absence of diary entry on a given day was treated as the absence of a bowel movement by the IVRS; programmatic IVRS study withdrawal

notifications were generated for patients that were noncompliant with the IVRS for the same criteria as the absence of a bowel movement. Eligible patients were male or female aged 18 to 65 years who met the Rome III criteria for IBS-D,3 and who reported a mean daily WAP score of ≥3.0 (on a 0−10 numerical rating scale, where 0 indicates no pain and 10 worst pain imaginable) and mean daily stool consistency score of ≥5.5 on the Bristol Stool Scale (1 = hard, lumpy stools and 7 = watery, liquid stools) in the cAMP week before randomization. Patients were also required to have had a colonoscopy within the past 5 years for any alarm feature, such as weight loss, nocturnal symptoms, familial history of colon cancer, or blood mixed with stool. Patients with histories of inflammatory bowel disease, celiac disease, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, impaired intestinal circulation, major vein thrombophlebitis, hypercoagulable states, major gastric, hepatic, pancreatic, or intestinal surgery, or evidence of significant hepatic or renal disease were excluded.