The Plecanatide Irritable Bowel Syndrome With Constipation Study (IBS-C)
The Plecanatide Irritable Bowel Syndrome With Constipation Study (IBS-C)
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in
 patients with IBS-C.
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in
 patients with IBS-C. Patients will undergo a Screening Period to determine eligibility. After
 completing a Screening Visit patients will undergo a 2-week Pre-Treatment assessment using
 the Interactive Voice Response System (IVRS) during which they will complete daily
 assessments of bowel movements (BMs), stool consistency (Bristol Stool Form Scale- BSFS),
 abdominal pain or abdominal discomfort and other symptoms associated with IBS-C. Data from
 the two-week IVRS Pre-treatment assessment are used to define the patient's baseline from
 which change will be determined. Patients who meet all entry criteria will be randomized to
 one of five treatment groups ( 0.3mg,1.0mg,3.0mg,9mg,or Placebo) on Day 1 of the Treatment
 Period. Patients will take an oral dose of study drug daily (QD) for 12 weeks and continue
 the daily IVRS diaries (BMs, abdominal pain, other symptoms). On Weeks 2, 4, 8, and 12,
 patients will return to the clinic to undergo safety and efficacy assessments. For 2 weeks
 after completing dosing, (i.e., Post-Treatment Period), patients will continue to complete
 daily IVRS diaries. Patients will then return to the clinical site for a final follow-up
 visit (End of Study Visit). The planned duration of participation in this study will be
 approximately 112 days from signing of informed consent through post-treatment or 145 days if
 30 day washout of a prohibited concomitant medication or stabilization of a medical condition
 is required before Pre-Treatment (up to 148 days, with all windows considered).
Inclusion Criteria:

 -  Male or female aged 18-75, inclusive

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

 -  Meets modified Rome III criteria for irritable bowel syndrome with constipation which
 includes abdominal pain or discomfort for at least 3 days/month in the last 3 months
 with symptom onset for at least 6 months.

 -  Less than 3 CSBMs and less than 6 SBMs per week during the last 3 months.

 -  Hard or lumpy stools ≥ 25 % of defecations

 -  Patient has average abdominal pain intensity scores ≥ 3 (scale 0-10)for the combined 2
 week pre-treatment period

 -  Patient is willing to discontinue use of supplemental fiber, laxatives, prescription
 and nonprescription medications, herbal or dietary supplements intended to treat
 constipation during the screening, pre-treatment, treatment and 2-week post-treatment
 periods

 -  Willing to maintain a stable diet during the study.

 -  Patients with hemorrhoids and/or diverticulosis (NOT diverticulitis) CAN be entered
 into the study.

 Exclusion Criteria:

 -  Loose stool (mushy) or watery stool in the absence of any laxative or prohibited
 medicine for > 25% of BMs during the 3 months prior to screening visit OR during the
 14 day pre-treatment period

 -  Patient has diarrhea-predominant or mixed ( diarrhea and constipation cycling or
 diarrhea and normal cycling) IBS.

 -  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: structural abnormality of the GI tract or gastric bypass
 surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis,
 diverticulitis, anal fissures or any disease or condition that can affect GI motility
 or defecation or can be 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.