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

Phase 2
Completed
Conditions
Irritable Bowel Syndrome Characterized by Constipation
Interventions
Drug: Placebo
Registration Number
NCT01722318
Lead Sponsor
Bausch Health Americas, Inc.
Brief Summary

This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in patients with IBS-C.

Detailed Description

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
428
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo, one tablet by mouth daily for 12 weeks
Plecanatide 0.3mgPlecanatidePlecanatide 0.3mg, one tablet by mouth daily for 12 weeks
Plecanatide 1.0mgPlecanatidePlecanatide 1.0mg one tablet by mouth daily for 12 weeks
Plecanatide 3.0mgPlecanatidePlecanatide 3.0mg, one tablet by mouth daily for 12 weeks
Plecanatide 9.0mgPlecanatidePlecanatide 9.0mg, one tablet by mouth daily for 12 weeks
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)12 weeks Treatment Period

The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population)12-Week Treatment Period

Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst.

Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population)12-Week Treatment Period

The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale \[BSFS\] from 1 to 7.

1. = separate hard lumps like nuts (difficult 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)

Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population)12-Week Treatment Period

The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe

Trial Locations

Locations (97)

San Marcus Research Clinic, Inc.

🇺🇸

Miami, Florida, United States

Genoma Research Group, Inc.

🇺🇸

Miami, Florida, United States

South Medical Research Group, Inc.

🇺🇸

Miami, Florida, United States

Oklahoma Foundation for Digestive Research

🇺🇸

Oklahoma City, Oklahoma, United States

Lynn Health Science Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Quality Research, Inc.

🇺🇸

San Antonio, Texas, United States

New River Valley Research Institute

🇺🇸

Christiansburg, Virginia, United States

Lynn Institute of the Ozarks

🇺🇸

Little Rock, Arkansas, United States

Eastern Research, Inc

🇺🇸

Hialeah, Florida, United States

Columbus Clinical Services, LLC

🇺🇸

Miami, Florida, United States

Gastrointestinal Associates, PA

🇺🇸

Jackson, Mississippi, United States

Health Awareness, Inc.

🇺🇸

Jupiter, Florida, United States

Urology Center of Florida

🇺🇸

Pompano Beach, Florida, United States

Clinical Research of Central Florida

🇺🇸

Winter Haven, Florida, United States

CTL Research

🇺🇸

Eagle, Idaho, United States

Medex Healthcare Research, Inc

🇺🇸

Chicago, Illinois, United States

Centex Studies, Inc.

🇺🇸

Houston, Texas, United States

Clinical Research Institute of Michigan, LLC

🇺🇸

Chesterfield, Michigan, United States

Heartland Research Associates, LLC

🇺🇸

Augusta, Kansas, United States

MGG Group Co., Inc., Chevy Chase Clinical Research

🇺🇸

Chevy Chase, Maryland, United States

Center for Digestive Health

🇺🇸

Troy, Michigan, United States

Carolina Digestive Health Associates

🇺🇸

Davidson, North Carolina, United States

St. Louis Center for Clinical Research

🇺🇸

Saint Louis, Missouri, United States

Central Sooner Research

🇺🇸

Norman, Oklahoma, United States

Montana Health Research Institute, Inc.

🇺🇸

Billings, Montana, United States

MediSpect Medical Research, LLC

🇺🇸

Boone, North Carolina, United States

Asheville Gastroenterology Associates, PA

🇺🇸

Asheville, North Carolina, United States

Internal Medical Associates of Grand Island, PC

🇺🇸

Grand Island, Nebraska, United States

On Site Clinical, LLC

🇺🇸

Charlotte, North Carolina, United States

Great Lakes Gastroenterology

🇺🇸

Mentor, Ohio, United States

LeBauer Research Associates, P.A.

🇺🇸

Greensboro, North Carolina, United States

Clinical Trials of North Carolina, LLC

🇺🇸

Cary, North Carolina, United States

Hometown Urgent Care and Occupational Health

🇺🇸

Columbus, Ohio, United States

Franklin Gastroenterology, PLLC

🇺🇸

Franklin, Tennessee, United States

Consultants in Gastroenterology

🇺🇸

Columbia, South Carolina, United States

Texas Tech Medical Center

🇺🇸

El Paso, Texas, United States

Physician PrimeCare Research Institute, PLLC dba Health Texas Research Institute

🇺🇸

San Antonio, Texas, United States

Pioneer Research Solutions, Inc.

🇺🇸

Sugar Land, Texas, United States

Horizons Clinical Research Center, LLC

🇺🇸

Denver, Colorado, United States

Medical Center for Clinical Research

🇺🇸

San Diego, California, United States

Lynn Institute of the Rockies

🇺🇸

Colorado Springs, Colorado, United States

Advanced Research Associates, LLC

🇺🇸

Glendale, Arizona, United States

Elite Clinical Trials, LLC

🇺🇸

Phoenix, Arizona, United States

SC Clinical Research, Inc.

🇺🇸

Garden Grove, California, United States

Advanced Rx Clinical Research, Inc.

🇺🇸

Artesia, California, United States

Genova Clinical Research, Inc.

🇺🇸

Tucson, Arizona, United States

GW Research, Inc.

🇺🇸

Chula Vista, California, United States

Consultants for Clinical Research of South Florida

🇺🇸

Boynton Beach, Florida, United States

Meridien Research

🇺🇸

Tampa, Florida, United States

Quality Clinical Research, Inc.

🇺🇸

Omaha, Nebraska, United States

Memphis Gastroenterology Group, PC

🇺🇸

Germantown, Tennessee, United States

Accord Clinical Research, LLC

🇺🇸

Port Orange, Florida, United States

Medoff Medical / Vital re:Search

🇺🇸

Greensboro, North Carolina, United States

Digestive Health Specialists of the Southeast

🇺🇸

Dothan, Alabama, United States

Cahaba Research

🇺🇸

Birmingham, Alabama, United States

Adobe Clinical Research, LLC

🇺🇸

Tucson, Arizona, United States

Community Clinical Trials

🇺🇸

Orange, California, United States

Anaheim Clinical Trials, LLC

🇺🇸

Anaheim, California, United States

Healthcare Partners Medical Group

🇺🇸

Pasadena, California, United States

Grossmont Center for Clinical Research

🇺🇸

La Mesa, California, United States

Jupiter Research, Inc.

🇺🇸

Jupiter, Florida, United States

Medical Research Unlimited, LLC

🇺🇸

Hialeah, Florida, United States

MNH Surgical Center

🇺🇸

Maitland, Florida, United States

Palm Beach Research Center

🇺🇸

West Palm Beach, Florida, United States

Mount Vernon Clinical Research, LLC

🇺🇸

Sandy Springs, Georgia, United States

Georgia Regents University

🇺🇸

Augusta, Georgia, United States

Louisiana Research Center, LLC

🇺🇸

Shreveport, Louisiana, United States

Research Integrity, LLC

🇺🇸

Owensboro, Kentucky, United States

IHA Chelsea Family & Internal Medicine

🇺🇸

Chelsea, Michigan, United States

Novex Clinical Research, LLC

🇺🇸

New Bedford, Massachusetts, United States

The Center for Clinical Trials

🇺🇸

Biloxi, Mississippi, United States

Prism Research

🇺🇸

Saint Paul, Minnesota, United States

St. Luke's Hospital

🇺🇸

New York, New York, United States

Cumberland Research Associates, LLC

🇺🇸

Fayetteville, North Carolina, United States

Wake Research Associates, LLC

🇺🇸

Raleigh, North Carolina, United States

Options Health Research, LLC

🇺🇸

Tulsa, Oklahoma, United States

Southeast Medical Research

🇺🇸

North Charleston, South Carolina, United States

ClinSearch, LLC

🇺🇸

Chattanooga, Tennessee, United States

North Texas Family Medicine

🇺🇸

Plano, Texas, United States

Blue Ridge Medical Research/Gastroenterology Associates of Central Virginia

🇺🇸

Lynchburg, Virginia, United States

Arrowhead Family Health Center PC dba Arrowhead Health Centers

🇺🇸

Glendale, Arizona, United States

Memorial Research Medical Clinic d/b/a Orange Country Research Center

🇺🇸

Tustin, California, United States

Chattanooga Medical Research LLC

🇺🇸

Chattanooga, Tennessee, United States

Gastroenterology Research of New Orleans

🇺🇸

Hammond, Louisiana, United States

Ridgeview Research

🇺🇸

Chaska, Minnesota, United States

Delta Research Partners, LLC

🇺🇸

Bastrop, Louisiana, United States

Associates in Gastroenterology

🇺🇸

Hermitage, Tennessee, United States

Bay State Clinical Trials, Inc.

🇺🇸

Watertown, Massachusetts, United States

Palmetto Clinical Research

🇺🇸

Summerville, South Carolina, United States

Boston Clinical Trials

🇺🇸

Boston, Massachusetts, United States

Rockford Gastroenterology Associates

🇺🇸

Rockford, Illinois, United States

Compass Research, LLC

🇺🇸

Orlando, Florida, United States

PMG Research of Winston-Salem, LLC

🇺🇸

Winston-Salem, North Carolina, United States

Women Under Study, LLC

🇺🇸

New Orleans, Louisiana, United States

Austin Center for Clinical Research

🇺🇸

Austin, Texas, United States

DCT-AACT, LLC dba Discovery Clinical Trials

🇺🇸

Austin, Texas, United States

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