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

Phase 3

Completed

Conditions: Irritable Bowel Syndrome Characterized by Constipation

Interventions: Drug: Plecanatide
Drug: Placebo

Registration Number: NCT02387359

Lead Sponsor: Bausch Health Americas, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1054

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 > 35 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
6.0 mg plecanatide	Plecanatide	Plecanatide 6.0 mg dosed daily for 12 weeks
3.0 mg plecanatide	Plecanatide	Plecanatide 3.0 mg dosed daily for 12 weeks
Matching placebo	Placebo	Placebo dosed daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Number of Abdominal Pain Responders for at Least 6 of 12 Treatment Weeks	12 Weeks	An Abdominal Pain Intensity Responder was a patient who had a decrease of 30% from baseline for abdominal pain intensity. Baseline was 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.
Number of Stool Frequency Responder for at Least 6 of the 12 Treatment Weeks	12 weeks	A Stool Frequency Responder is defined as 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.
Number of Overall Responders - ITT Population	12 Weeks	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 one complete spontaneous bowel movement in the same week) for at least 6 of the 12 treatment weeks.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Abdominal Pain	Baseline and 12-Week	Change from baseline in abdominal pain as measured with an 11-point (0-10) Numerical Rating Scale from 0 (No) to 10 (Worst Possible). 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.
Change From Baseline in Stool Consistency	Baseline and 12-Week	Change from baseline in stool consistency based upon the Bristol Stool Form Scale (BSFS) Rating 1 to 7. 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: 1. Separate hard lumps, like nuts (hard to pass) 2. Sausage-shaped but lumpy 3. Like a sausage but with cracks on its surface 4. Like a sausage or snake, smooth and soft 5. Soft blobs with clear-cut edges (passed easily) 6. Fluffy pieces with ragged edges, a mushy stool 7. Watery, no solid pieces, entirely liquid
Number of Patients With a SBM Within 24 Hours After the First Dose	Up to 24 hours after first dose of study drug	Number of patients with a SBM (spontaneous bowel movement) within 24 hours after the first dose of study drug
Number of Sustained Efficacy Responders	12 weeks	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.
Change From Baseline in Straining	Baseline and 12-week	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).
Change From Baseline in CSBM Frequency Rate	Baseline and 12-Week	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.