a 12-week study with a 4-week randomized withdrawal period to evaluate the efficacy and safety of tenapanor for the treatment of ibs-c

Conditions: Constipation Predominant Irritable Bowel Syndrome

Summary: this phase 3, 12-week, randomized, double-blind, placebo-controlled, multi-center study will evaluate the safety and efficacy of tenapanor in subjects with constipation-predominant irritable bowel syndrome (ibs-c) as defined by the rome iii criteria and who have active disease as determined after a two-week screening period. subjects who qualify and are randomized into the study will either receive 50mg bid of tenapanor or placebo bid for 12 week treatment period and then undergo a 4 week placebo controlled randomized withdrawal.

during the 12-week treatment period, subjects will record daily assessments including: frequency and timing of bowel movements; sensation and complete bowel emptying; consistency of bowel movements; degree of straining, worst abdominal pain, abdominal discomfort, abdominal bloating, abdominal fullness and abdominal cramping. subjects will also record weekly assessments including: adequate relief of ibs severity, and constipation severity. at the end of the 12-week treatment period, there will be a 4-week randomized withdrawal period in which subjects who complete the study in tenapanor group will be randomized to either tenapanor 50mg bid or placebo bid (1:1) and subjects who complete the study in the placebo group will be assigned to receive tenapanor 50mg bid.

Eligibility criteria:
inclusion criteria: * 18 to 75 years old * females must be of non-childbearing potential; if of child-bearing potential, must have negative pregnancy test and confirm the use of one of the appropriate means of contraception. * males must agree to use an appropriate method of barrier contraception or have documented surgical sterilization * subject meets definition of ibs-c using rome iii criteria for the diagnosis of ibs * a colonoscopy based on aga guidelines; every 10 years at ≥ 50 years old, or the occurrence of any warning signs exclusion criteria: * functional diarrhea as defined by rome iii criteria * ibs with diarrhea (ibs-d), mixed ibs (ibs-m), or unsubtyped ibs as defined by rome iii criteria * diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the gi tract within 6 months prior to screening, or active disease within 6 months prior to screening; including but not limited to cancer, inflammatory bowel disease, diverticulitis, duodenal ulcer, erosive esophagitis, gastric ulcer, pancreatitis (within 12 months of screening), cholelithiasis, amyloidosis, ileus, non-controlled gerd, gastrointestinal obstruction, ischemic colitis or carcinoid syndrome. * subject has a history or current evidence of laxative abuse (in the clinical judgment of the physician) * hepatic dysfunction (alt \[sgpt\] or ast \[sgot\] \>2.5 times the upper limit of normal) or renal impairment (serum creatinine \> 2mg/dl) * any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year * any surgery on the stomach, small intestine or colon, excluding appendectomy or cholecystectomy (unless within 60 days of screening visit)