Second Plecanatide Study In Irritable Bowel Syndrome With Constipation (IBS-C)

Study Overview
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Brief Summary
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This study in patients with IBS-C is a randomized, double-blind, placebo-controlled, parallel-group clinical trial with 12 weeks of study drug therapy.

Detailed Description
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This study in patients with IBS-C is a randomized, double-blind, placebo-controlled, parallel-group clinical trial with 12 weeks of study drug therapy. Screening/Baseline: Patients will undergo an up to 28-day Screening/Baseline period to allow for any necessary diagnostic procedures, allow for required washout of medications and to determine study eligibility. If otherwise eligible based on screening criteria, patients will undergo a 2-week baseline assessment using an electronic diary where they will record daily assessments of bowel movements (BMs), stool consistency (Bristol Stool Form Scale-BSFS), abdominal pain and other IBS-related symptoms. Data from the two-week electronic diary assessment just prior to the randomization visit will be used to confirm IBS-C and study eligibility as well as define the patient's baseline from which change will be determined. Treatment: Patients who meet all entry criteria will be randomized (1:1:1) to one of three blinded treatment groups on Day 1 of the Treatment period. Patients will take an oral dose of study drug OD for 12 weeks and continue the daily electronic diaries (BMs, rescue medication use, abdominal pain, and other symptoms). During treatment weeks 4, 8, and 12, patients will return to the clinic to undergo safety and efficacy assessments. Post-Treatment: For 2 weeks after completing dosing, patients will continue to complete daily electronic diaries. Patients will then return to the clinical site for a final follow-up visit during Week 14 following randomization. The planned duration of participation in this study will be at least 116 days from signing of informed consent through post-treatment or up to approximately 135 days with visit windows considered.

Official Title
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Second Phase 3 Randomized, 12-Week, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Conditions
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Irritable Bowel Syndrome Characterized by Constipation

Intervention / Treatment
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* Drug: Plecanatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Adult patients between the ages of 18 and 85 years (inclusive) with a diagnosis of IBS based on ROME III diagnostic criteria and meeting criteria for diagnosis of the constipation predominant subtype - IBS-C Exclusion Criteria: Refusal or inability to sign informed consent for the trial Refusal or inability to complete daily Episodic (real-time) BM / RM calls, End of Day daily Calls, and/or complete electronic questionnaires BMI ≥ 40 or < 18 Women of child bearing potential who refuse to use an acceptable method of birth control for the duration of the trial Women who are pregnant or lactating Diagnosis of IBS-D or IBS-M Organic or obstructive disease of the small or large intestine Use of laxatives other than the study-supplied rescue medication (Dulcolax®, bisacodyl) Use of a prohibited concomitant medication within the time frame prior to screening outlined in the study protocol for that medication Unstable medical illness Bilirubin > 3X ULN in the absence of a conjugation defect Any laboratory value > 3X ULN unless discussed and approved by the study Medical Monitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 3.0 mg plecanatide<br>Plecanatide 3.0 mg dosed daily for 12 weeks | Drug: Plecanatide<br> <br> |
| Active Comparator: 6.0 mg plecanatide<br>Plecanatide 6.0 mg dosed daily for 12 weeks | Drug: Plecanatide<br> <br> |
| Active Comparator: Matching placebo<br>Placebo dosed daily for 12 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Overall Responders - ITT Population | An Overall Responder was a patient who was a weekly responder (i.e., decrease of 30% from baseline for abdominal pain intensity and an increase of at least 1 complete spontaneous bowel movement in the same week) for at least 6 of the 12 treatment weeks. | 12 weeks | 
| Number of Abdominal Pain Responders for at Least 6 of 12 Treatment Weeks | An Abdominal Pain Intensity Responder was a patient who had a decrease of 30 % from baseline for abdominal pain intensity. Baseline is the mean of non-missing abdominal pain scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. | 12 Weeks | 
| Number of Stool Frequency Responder for at Least 6 of the 12 Treatment Weeks | A Stool Frequency Responder was a patient who experienced an increase of at least one CSBM (complete spontaneous bowel movement) per week from baseline. Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Sustained Efficacy Responders | A Sustained Efficacy Responder was a patient who was an Overall Responder who also was a Weekly Responder, i.e., decreased of 30% from baseline for abdominal pain intensity and increased of at least one CSBM (complete spontaneous bowel movement) in the same week for at least 2 of the 4 weeks in month 3 of the Treatment Period. | 12 Weeks | 
| Change From Baseline in Stool Consistency | Change from baseline in stool consistency based upon the Bristol Stool Form Scale (BSFS). Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. BSFS Rating 1 to 7: Separate hard lumps, like nuts (hard to pass) Sausage-shaped but lumpy Like a sausage but with cracks on its surface Like a sausage or snake, smooth and soft Soft blobs with clear-cut edges (passed easily) Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces, entirely liquid | Baseline and 12-Week | 
| Change From Baseline in Straining | Change from baseline in Straining Score over the 12-week treatment period. Baseline was the mean of non-missing straining scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The severity of straining during a bowel movement was measured using an 11-point scale (0-10 rating; 0 = no straining; 10 = worst straining). | Baseline and 12-Week | 
| Change From Baseline in CSBMs (CSBMs/Week)Complete Spontaneous Bowel Movement | Change from baseline over the 12-week Treatment Period in CSBM (Complete Spontaneous Bowel Movement) Frequency Rate (CSBMs/Week). Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. | Baseline and 12-Week | 
| Number of Patients With a SBM Within 24 Hours After First Dose of Study Medication | A responder was any patient with a SBM within 24 hours after the first dose of study drug. | Up to 24 hours after the first dose of study drug | 
| Change From Baseline in Abdominal Pain | Change from baseline in abdominal pain as measured with an 11-point (0-10) Numerical Rating Scale from 0 (None) to 10 (Worst Possible). Baseline was the mean of the non-missing abdominal pain scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The average daily abdominal pain score was the average of the non-missing worst daily abdominal pain scores (on a 0 to 10 scale) in the given week. | Baseline and 12-Week |