A 26-Week Study to Evaluate the Efficacy and Safety of Tenapanor in IBS-C

During the 26-week double-blind treatment period, subjects will record daily assessments
including: frequency and timing of bowel movements; sensation of complete bowel emptying;
consistency of bowel movements; degree of straining, worst abdominal pain, abdominal
discomfort, abdominal bloating, abdominal fullness and abdominal cramping; and use and timing
of rescue medication. Subjects will also record weekly assessments including: adequate relief
of IBS symptoms, degree of relief of IBS symptoms, IBS severity, and constipation severity.

Inclusion Criteria:

- Males or females aged 18 to 75 years, inclusive

- 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 appropriate methods 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

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 or carcinoid syndrome.

- Potential CNS cause of constipation (e.g., Parkinson's disease, spinal cord injury, or
multiple sclerosis)

- Subject has a history or current evidence of laxative abuse (in the clinical judgment
of physician)

- Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or
renal impairment (serum creatinine >2 mg/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 and
cholecystectomy (unless within 60 days of screening visit)