The Plecanatide Chronic Idiopathic Constipation (CIC) Study

Inclusion Criteria:

• Male or female aged 18-75, inclusive

• Body Mass Index = 18-35 kg/m2, inclusive

• Meets modified Rome III criteria for functional chronic idiopathic constipation for atleast 3 months with symptom onset for at least 6 months. Note: For this trial,patients with manual maneuvers required for >25% of defecations will not be eligiblefor participation.

• Less than 3 CSBMs per week at baseline and during pretreatment

• Completed a colonoscopy in accordance with medical guidelines as appropriate, with noclinically significant findings

• Patient is willing to discontinue use of supplemental fiber, laxatives, prescriptionand nonprescription medications, herbal or dietary supplements intended to treatconstipation during the screening, pre-treatment, treatment and 2-week post-treatmentperiods

• Willing to maintain a stable diet during the study.

• Patients with hemorrhoids and/or diverticulosis (NOT diverticulitis) CAN be enteredinto the study.

Exclusion Criteria:

• Loose stool (mushy) or watery (Bristol score- 6 or 7) stool in the absence of anylaxative or prohibited medicine for > 25% of BMs during the 3 months prior toscreening visit OR during the 14 day treatment period

• Patient meets the Rome III criteria for Irritable Bowel Syndrome (IBS-C)

• Active peptic ulcer disease not adequately treated or not stable

• History of cathartic colon, laxative, enema abuse, or ischemic colitis.

• Fecal impaction within 3 months of screening

• Patient has had /has any: diseases or conditions associated with constipation (GI orCNS), structural abnormality of the GI tract or gastric bypass surgery, pelvic floordysfunction, pseudo-obstruction, active infectious gastritis, diverticulitis, analfissures or any disease or condition that can affect GI motility or defecation or canbe associated with abdominal pain

• Unexplained and clinically significant "alarm symptoms" including lower GI bleeding,iron-deficiency anemia, weight loss or systemic signs of infection or colitis.

• Major surgery within 60 days of screening.