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

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.

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)