Efficacy and Safety of Plecanatide in Children 6 to <18 Years With Irritable Bowel Syndrome With Constipation (IBS-C) ((IBS-C))

A Randomized, Double-blind, Placebo-Controlled, Dose Ranging, Parallel-Group Study of the Efficacy and Safety of Plecanatide in Children 6 to <18 Years of Age With Irritable Bowel Syndrome With Constipation (IBS-C)

The goal of this clinical trial is to learn if plecanatide can improve bowel function and relieve symptoms of irritable bowel syndrome with constipation (IBS-C) in children and adolescents aged 6 to <18 years. The main questions it aims to answer are:

• Does plecanatide increase the number of spontaneous bowel movements (SBMs) compared to placebo?
• Is plecanatide safe and well tolerated in this pediatric population? Researchers will compare plecanatide at different doses to a placebo (a look-alike substance with no active drug) to see if plecanatide improves bowel function.

Participants will:

• Take plecanatide or placebo orally once daily for 4 weeks
• Complete daily symptom diaries
• Attend clinic visits for assessments and safety checks

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Constipation
• Intervention / Treatment: Drug: Plecanatide; Drug: Matching placebo

Detailed Description

This study is a randomized, double-blind, placebo-controlled, dose-ranging clinical trial designed to evaluate the safety, efficacy, and pharmacokinetics of plecanatide in pediatric patients aged 6 to <18 years with irritable bowel syndrome with constipation (IBS-C). IBS-C is a condition that causes abdominal pain and infrequent, hard bowel movements.

The study includes two age cohorts:

Group A: 6 to 11 years Group B: 12 to <18 years

Participants are randomly assigned to receive one of four plecanatide doses (0.5 mg, 1.0 mg, 2.0 mg, or 3.0 mg) or placebo. All treatments were taken orally once daily for 4 weeks following a 28-day screening/baseline period. After treatment, participants were followed for 2 weeks.

The primary objective is to determine whether plecanatide increases the number of spontaneous bowel movements (SBMs) compared to placebo.

Secondary objectives include:

Time to first bowel movement after starting treatment Changes in stool consistency Changes in abdominal pain and discomfort Overall safety and tolerability of plecanatide

Safety assessments include monitoring adverse events, laboratory tests, and treatment compliance. Participants recorded daily bowel habits and symptoms in an electronic diary and attended scheduled clinic visits for evaluations.

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Saraland, Alabama, United States, 36571
      • Bausch Site 178
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Bausch Site 176
  • California
    • Corona, California, United States, 92879
      • Bausch Site 160
    • Garden Grove, California, United States, 92845
      • Bausch Site 147
    • Los Angeles, California, United States, 90036
      • Bausch Site 142
    • Ventura, California, United States, 93003
      • Bausch Site 143
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Bausch Site 175
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Bausch Site 197
  • Florida
    • Doral, Florida, United States, 33122
      • Bausch Site 135
    • Hialeah, Florida, United States, 33012
      • Bausch Site 190
    • Miami, Florida, United States, 33126
      • Bausch Site 150
    • Miami, Florida, United States, 33134
      • Bausch Site 130
    • Miami, Florida, United States, 33136
      • Bausch Site 165
    • Tampa, Florida, United States, 33607
      • Bausch Site 110
  • Georgia
    • Atlanta, Georgia, United States, 30315
      • Bausch Site 174
    • Atlanta, Georgia, United States, 30342
      • Bausch Site 132
    • Stockbridge, Georgia, United States, 30281
      • Bausch Site 148
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Bausch Site 115
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Bausch Site 139
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Bausch Site 192
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Bausch Site 172
    • Crowley, Louisiana, United States, 70526
      • Bausch Site 180
    • Lafayette, Louisiana, United States, 70508
      • Bausch Site 112
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Bausch Site 220
  • Ohio
    • Akron, Ohio, United States, 44308
      • Bausch Site 145
    • Cleveland, Ohio, United States, 44106
      • Bausch Site 194
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Bausch Site 111
  • Texas
    • Austin, Texas, United States, 78723
      • Bausch Site 195
    • Cedar Park, Texas, United States, 78613
      • Bausch Site 225
    • Dallas, Texas, United States, 75243
      • Bausch Site 173
    • Houston, Texas, United States, 77030
      • Bausch Site 193
    • Houston, Texas, United States, 77087
      • Bausch Site 170
    • San Antonio, Texas, United States, 78215
      • Bausch Site 140
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Bausch Site 120
  • Washington
    • Bellevue, Washington, United States, 98007
      • Bausch Site 146

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

A patient will be eligible for study participation if he or she meets all of the following criteria:

1. Male or female child or adolescent age 6 to < 18;
2. Meets ROME IV criteria for child/adolescent IBS-C defined as:

For at least 2 months before diagnosis the patient has had:

1. Abdominal pain at least 4 days per month associated with one or more of the following:

   1. Related to defecation
   2. A change in frequency of stool
   3. A change in form (appearance) of stool;
2. The pain does not resolve with resolution of the constipation (children in whom the pain resolves have functional constipation, not irritable bowel syndrome);
3. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition
4. More than one-fourth (25%) of bowel movements with Bristol stool form types 1 or 2 and less than one-fourth (25%) of bowel movements with Bristol stool form types 6 or 7 on the BSFS or 4 or 5 on the mBSFS-C;

3. Patient's parent/guardian/LAR is able to voluntarily provide written, signed, and dated consent and patient is able to voluntarily provide assent as per IRB guidance; 4. Patient and patient's parent/guardian/LAR demonstrates an understanding, ability, and willingness to fully comply with protocol requirements and study procedures (e.g., acceptance of venipuncture, acceptance of urine drug screen for opiates, visit schedule, complete daily electronic diary reporting).

EXCLUSION CRITERIA

A patient will be excluded from the study if he or she meets any of the following criteria:

1. The patient has a mental age <4 years in the investigator's opinion;
2. The patient has previously been diagnosed with anorectal malformations, neurological deficits, or anatomical anomalies that would constitute a predisposition to constipation;
3. The patient currently requires iron supplements, amitriptyline, or other tricyclic antidepressants for depression, opioid-containing medications or compounds for pain, or has other conditions that require medications known to cause constipation. A patient with an onset of constipation prior to the use of these medications and who has been on a stable dose for at least 8 weeks prior to Screening might be considered eligible for this study if the investigator deems these medications do not significantly contribute to the patient's constipation. Screening of these patients needs to be approved by the medical monitor and the sponsor;
4. The patient is pregnant or lactating;

5. Females age 12 to < 18 or females age 6 to 11 of childbearing potential (defined as post menarche) who does not agree to practice one of the following medically acceptable methods of birth control throughout the study;

   • Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before study drug administration.
   • Total abstinence from sexual intercourse (since the last menses before study drug administration
   • Intrauterine device.
   • Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream.
6. The patient follows a diet not considered normal by the investigator for the patient's age, relative to variety of food, caloric content, and quantity. The patient must have been on a stable diet for at least 30 days prior to Screening;
7. The patient's mobility or normal exercise tolerance is compromised in the investigator's opinion;
8. The patient has a history of an eating disorder;
9. The patient has clinical or laboratory signs and symptoms of significant cerebral, respiratory, renal, hepatobiliary, pancreatic, intestinal (including acute appendicitis, inflammatory bowel disease, or undiagnosed abdominal pain), endocrinologic, or infectious disease that in the investigator's judgment could interfere with study assessments or completion of the study. (Note: A patient with a history of thyroid disease may be enrolled if he or she has normal T3 and T4 at Screening. If the patient is taking medication for active thyroid disease, his or her T3 and T4 level must be within normal limits and the dose of any medication used to treat it must be stable for at least 30 days prior to Screening);
10. The patient has any other medical condition or is receiving concomitant medication or therapy that would in the investigator's opinion compromise his or her safety or compliance with the study protocol or compromise data collection;
11. The patient has a history or evidence of drug or alcohol abuse in the 12 months before Screening;
12. The patient has a hypersensitivity, allergy, or contraindication to plecanatide;
13. The patient has received any experimental drug, including linaclotide and lubiprostone, or experimental therapy within 30 days of study start;
14. The patient is unable to tolerate protocol-prescribed rescue medication (Dulcolax®), or unwilling to use it as the only laxative for the duration of the trial;
15. The patient has taken a medication considered to be a protocol-defined prohibited prior or concomitant medication or supplement as defined in section 3.3.2;
16. The patient and his or her caregiver are unable to communicate well with the study staff and comply with the study requirements (restrictions, appointments, and examination schedule). (The patient/caregiver must be able to complete required Daily BM and Symptom diary entries during the Screening/Baseline period and for the duration of the study. The patient/caregiver must also agree to provide contact information to receive daily reminders should the patient not complete the daily electronic diary entries or require password resets);
17. The patient has been screened for or participated in this or another Synergy study in the past;

18. The patient has a sibling that is currently participating or has participated in another Synergy study.

    Exclusion Criteria Based on Baseline Diary Entries

19. Patient reports having more than 1 loose, mushy stool (Diary-recorded stool consistency of 6 on the Bristol Stool Form Scale (BSFS or 4 on the modified Bristol Stool Form Scale for Children [mBSFSC]) or any watery stool (Diary-recorded stool consistency of 7 on the BSFS or 5 on the mBSFS-C) with any SBM that occurred in the absence of laxative use on the calendar day of the BM or the calendar day before the BM during each 7-day (week) period before the randomization day and up to the day of randomization;
20. ≥ 3 CSBMs per week for either week of the 2-week baseline diary assessment immediately preceding the randomization visit;
21. > 6 SBMs per week for either week of the 2-week baseline diary assessment immediately preceding the randomization visit;

22. Patient reports worst abdominal pain intensity (WAPI) scores in the 2-week baseline diary that meet either of the following:

    1. WAPI score of 0 on the 11-point Numeric Rating Scale or Wong-Baker Faces® Pain Rating Scale for more than two days during each week of the 2-week baseline diary period.
    2. An average WAPI < 3 for either of the two weeks of the baseline diary;
23. Completion of < 5 of the 7 required daily diary entries in each week of the 2-week baseline diary assessment immediately preceding the randomization visit;
24. Use of rescue medication (Dulcolax®, bisacodyl) for more than 2 days during either of the two weeks of the 2-week baseline diary assessment immediately preceding the randomization visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5 mg plecanatide; Plecanatide 0.5 mg Taken orally once daily for 4 weeks Group A: 6 to 11 years old	Drug: Plecanatide; Taken orally daily for 4 weeks; Other Names: Trulance
Experimental: 3.0 mg plecanatide; Plecanatide 3.0 mg Taken orally daily for 4 weeks Group B: 12 to < 18 years old	Drug: Plecanatide; Taken orally daily for 4 weeks; Other Names: Trulance
Experimental: 1.0 mg plecanatide - Group A; Plecanatide 1.0 mg Taken orally daily for 4 weeks Group A: 6 to 11 years old	Drug: Plecanatide; Taken orally daily for 4 weeks; Other Names: Trulance
Experimental: 2.0 mg plecanatide; Plecanatide 2.0 mg Taken orally daily for 4 weeks Group B: 12 to 18 Years of Age	Drug: Plecanatide; Taken orally daily for 4 weeks; Other Names: Trulance
Placebo Comparator: Matching placebo - Group A; Matching placebo Taken orally daily for 4 weeks Group A: 6 to 11 years old	Drug: Matching placebo; Taken orally daily for 4 weeks; Other Names: No other names
Experimental: 1.0 mg plecanatide - Group B; Plecanatide 1.0 mg Taken orally daily for 4 weeks Group B: ≥ 12 to < 18 Years of Age	Drug: Plecanatide; Taken orally daily for 4 weeks; Other Names: Trulance
Placebo Comparator: Matching Placebo - Group B; Matching placebo Taken orally daily for 4 weeks Group B: 12 to < 18 years old	Drug: Matching placebo; Taken orally daily for 4 weeks; Other Names: No other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups	Weekly SBM rate computed for each week	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups..	Weekly frequency was calculated as the number of abdominal pain episodes and abdominal discomfort episodes per week, based on daily diary entries. Baseline was the average weekly frequency during the 2-week baseline assessment period. Values shown are mean change from baseline (SD).	Baseline to Week 4
Change From Baseline in Severity of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups..	Severity of abdominal pain and abdominal discomfort was recorded daily using an electronic diary on a 0-10 numeric rating scale (0 = no pain/discomfort; 10 = worst possible). Weekly averages were calculated; baseline was the average score during the 2-week baseline period. Values shown are mean change from baseline.	Baseline to Week 4
Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM)	Weekly frequency of complete spontaneous bowel movements (CSBMs) was calculated based on daily diary entries. Baseline was the average weekly frequency during the 2-week baseline period. Values shown are mean change from baseline (SD) at end of 4 weeks of study.	Baseline to Week 6
Change From Baseline in Frequency of Bowel Movements (BM)	Weekly frequency of bowel movements (BMs) was calculated based on daily diary entries. Baseline was the average weekly frequency during the 2-week baseline period. Values shown are mean change from baseline (SD).	Baseline to Week 4
Time to First Bowl Movement (in Days)	This outcome was analyzed as a time-to-event variable (time to first complete spontaneous bowel movement), and confidence intervals were estimated using Kaplan-Meier methods.	Day 1 to first BM during Treatment Period
Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C)	Weekly stool consistency scores based on BSFS (≥12 years) or mBSFS-C (6-11 years). BSFS Scale is a 7 point scale, from Type 1 (Hard to pass) to Type 7 (entirely liquid). mBSFS-C is a 5 point scale, from Type 1 (hard to pass) to Type 5 (watery, no solid pieces).	Baseline to Week 4
Use of Rescue Medication	Number of rescue medication tablets (Dulcolax® 5 mg) used during the 4-week treatment period. Subjects were instructed to use rescue medication only if ≥72 hours had passed since last bowel movement.	Baseline to Week 4
Change From Baseline in Frequency of Fecal Incontinence	Weekly fecal incontinence episodes recorded in daily diary.	Baseline to Week 4
Change From Baseline in Severity of Defecation Pain	Severity of abdominal pain scored daily on a 0-10 numeric rating scale (0 = no pain, 10 = worst possible pain). Weekly averages were calculated from daily scores.	Baseline to Week 4
Change From Baseline in Frequency of Pain With Defecation	Pain with defecation was recorded in daily diaries as the number of episodes per week. Results represent the mean change from baseline in weekly frequency.	Baseline to Week 4
Change From Baseline in Frequency of Large Diameter Stools	Weekly frequency of large diameter stools recorded in daily diary.	Baseline to Week 4

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Study Director: John Lahey, Bausch Health

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2018
• Primary Completion (Actual): November 25, 2024
• Study Completion (Actual): November 25, 2024

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; plecanatide
• Other Study ID Numbers: SP304202-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No