Irritable Bowel Syndrome With Constipation
Conditions
Brief summary
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
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.
Interventions
DRUGPlecanatide
Taken orally daily for 4 weeks
DRUGMatching placebo
Taken orally daily for 4 weeks
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | Baseline to Week 4 | Weekly SBM rate computed for each week |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Severity of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Baseline to Week 4 | 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. |
| Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | Baseline to Week 6 | 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. |
| Change From Baseline in Frequency of Bowel Movements (BM) | Baseline to Week 4 | 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). |
| Time to First Bowl Movement (in Days) | Day 1 to first BM during Treatment Period | 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. |
| Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | Baseline to Week 4 | 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). |
| Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Baseline to Week 4 | 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). |
| Change From Baseline in Frequency of Fecal Incontinence | Baseline to Week 4 | Weekly fecal incontinence episodes recorded in daily diary. |
| Change From Baseline in Severity of Defecation Pain | Baseline to Week 4 | 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. |
| Change From Baseline in Frequency of Pain With Defecation | Baseline to Week 4 | 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. |
| Change From Baseline in Frequency of Large Diameter Stools | Baseline to Week 4 | Weekly frequency of large diameter stools recorded in daily diary. |
| Use of Rescue Medication | Baseline to Week 4 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.5 mg Plecanatide Plecanatide 0.5 mg Taken orally once daily for 4 weeks Group A: 6 to 11 years old | 30 |
| 1.0 mg Plecanatide - Group A Plecanatide 1.0 mg Taken orally daily for 4 weeks Group A: 6 to 11 years old | 29 |
| Matching Placebo - Group A Matching placebo Taken orally daily for 4 weeks Group A: 6 to 11 years old | 29 |
| 1.0 mg Plecanatide - Group B Plecanatide 1.0 mg Taken orally daily for 4 weeks Group B: 12 to 18 years old | 34 |
| 2.0 mg Plecanatide Plecanatide 2.0 mg Taken orally daily for 4 weeks Group B: 12 to \< 18 years old | 32 |
| 3.0 mg Plecanatide Plecanatide 3.0 mg Taken orally daily for 4 weeks Group B: 12 to \< 18 years old | 32 |
| Matching Placebo - Group B Matching placebo Taken orally daily for 4 weeks Group B: 12 to \< 18 years old | 32 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Non-Compliance with eDiary | 1 | 0 | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Non-Compliance with Study Drug | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Participant moved and was unable to complete study | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Matching Placebo - Group B | 3.0 mg Plecanatide | 0.5 mg Plecanatide | 2.0 mg Plecanatide | 1.0 mg Plecanatide - Group B | Matching Placebo - Group A | 1.0 mg Plecanatide - Group A |
|---|---|---|---|---|---|---|---|---|
| Age, Customized Age Group Group A: Age 6 to 11 | 88 Participants | 0 Participants | 0 Participants | 30 Participants | 0 Participants | 0 Participants | 29 Participants | 29 Participants |
| Age, Customized Age Group Group B: Age 12 to <18 | 130 Participants | 32 Participants | 32 Participants | 0 Participants | 32 Participants | 34 Participants | 0 Participants | 0 Participants |
| BMI at Screening | 22.385 kg/m^2 STANDARD_DEVIATION 6.035 | 23.74 kg/m^2 STANDARD_DEVIATION 4.867 | 23.26 kg/m^2 STANDARD_DEVIATION 6.23 | 19.82 kg/m^2 STANDARD_DEVIATION 4.961 | 23.66 kg/m^2 STANDARD_DEVIATION 4.46 | 24.85 kg/m^2 STANDARD_DEVIATION 7.129 | 19.64 kg/m^2 STANDARD_DEVIATION 5.59 | 20.87 kg/m^2 STANDARD_DEVIATION 6.678 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 177 Participants | 28 Participants | 27 Participants | 23 Participants | 24 Participants | 25 Participants | 23 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 4 Participants | 5 Participants | 7 Participants | 8 Participants | 9 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height at Screening (m) | 1.51 meters STANDARD_DEVIATION 0.159 | 1.63 meters STANDARD_DEVIATION 0.086 | 1.58 meters STANDARD_DEVIATION 0.079 | 1.37 meters STANDARD_DEVIATION 0.136 | 1.60 meters STANDARD_DEVIATION 0.097 | 1.63 meters STANDARD_DEVIATION 0.091 | 1.38 meters STANDARD_DEVIATION 0.131 | 1.36 meters STANDARD_DEVIATION 0.135 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 188 Participants | 30 Participants | 30 Participants | 26 Participants | 25 Participants | 28 Participants | 22 Participants | 27 Participants |
| Region of Enrollment United States | 218 Participants | 32 Participants | 32 Participants | 30 Participants | 32 Participants | 34 Participants | 29 Participants | 29 Participants |
| Sex: Female, Male Female | 126 Participants | 20 Participants | 20 Participants | 16 Participants | 20 Participants | 20 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 92 Participants | 12 Participants | 12 Participants | 14 Participants | 12 Participants | 14 Participants | 14 Participants | 14 Participants |
| Weight at Screening | 52.73 kilograms STANDARD_DEVIATION 20.231 | 63.60 kilograms STANDARD_DEVIATION 16.62 | 58.21 kilograms STANDARD_DEVIATION 16.223 | 37.53 kilograms STANDARD_DEVIATION 11.98 | 60.72 kilograms STANDARD_DEVIATION 14.05 | 66.35 kilograms STANDARD_DEVIATION 22.402 | 38.79 kilograms STANDARD_DEVIATION 17.07 | 39.55 kilograms STANDARD_DEVIATION 15.118 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 29 | 0 / 29 | 0 / 34 | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 2 / 30 | 5 / 29 | 1 / 29 | 7 / 34 | 3 / 32 | 3 / 32 | 2 / 32 |
| serious Total, serious adverse events | 0 / 30 | 0 / 29 | 0 / 29 | 0 / 34 | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
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
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | 0.6 Number of SBMs per week | Standard Deviation 2.24 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | 0.8 Number of SBMs per week | Standard Deviation 1.75 |
| Matching placebo - Group A | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | 0.6 Number of SBMs per week | Standard Deviation 1.53 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | 1.0 Number of SBMs per week | Standard Deviation 2.08 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | 1.1 Number of SBMs per week | Standard Deviation 2.2 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | .70 Number of SBMs per week | Standard Deviation 2.45 |
| Matching Placebo - Group B | Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency Over the 4 Week Treatment Period Compared to Placebo and Across Treatment Groups | -0.2 Number of SBMs per week | Standard Deviation 1.95 |
Secondary
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).
Time frame: Baseline to Week 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -2.7 Episodes per week | Standard Deviation 2.27 |
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -2.5 Episodes per week | Standard Deviation 2.18 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -2.2 Episodes per week | Standard Deviation 2.38 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -2.1 Episodes per week | Standard Deviation 2.35 |
| Matching placebo - Group A | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -1.4 Episodes per week | Standard Deviation 2.47 |
| Matching placebo - Group A | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -1.3 Episodes per week | Standard Deviation 2.44 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -1.3 Episodes per week | Standard Deviation 1.49 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -0.9 Episodes per week | Standard Deviation 1.59 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -1.6 Episodes per week | Standard Deviation 2.34 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -1.5 Episodes per week | Standard Deviation 2.22 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -1.4 Episodes per week | Standard Deviation 2.26 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -1.1 Episodes per week | Standard Deviation 2.03 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Pain | -1.6 Episodes per week | Standard Deviation 2.56 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Abdominal Pain and Abdominal Discomfort Over the 4-week Treatment Period Compared to Placebo and Across Treatment Groups.. | Frequency of Abdominal Discomfort | -1.3 Episodes per week | Standard Deviation 2.43 |
Secondary
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).
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Bowel Movements (BM) | 0.5 Number of BMs per week | Standard Deviation 2.24 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Bowel Movements (BM) | 0.8 Number of BMs per week | Standard Deviation 1.7 |
| Matching placebo - Group A | Change From Baseline in Frequency of Bowel Movements (BM) | 0.6 Number of BMs per week | Standard Deviation 1.52 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Bowel Movements (BM) | 0.8 Number of BMs per week | Standard Deviation 2.06 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Bowel Movements (BM) | 1.0 Number of BMs per week | Standard Deviation 2.23 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Bowel Movements (BM) | 0.8 Number of BMs per week | Standard Deviation 2.263 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Bowel Movements (BM) | 0 Number of BMs per week | Standard Deviation 2.05 |
Secondary
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.
Time frame: Baseline to Week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | 0.7 Change in Number of CSBMs per week | Standard Deviation 1.73 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | 0.2 Change in Number of CSBMs per week | Standard Deviation 0.75 |
| Matching placebo - Group A | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | 0.2 Change in Number of CSBMs per week | Standard Deviation 0.91 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | 0.4 Change in Number of CSBMs per week | Standard Deviation 0.85 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | 0.1 Change in Number of CSBMs per week | Standard Deviation 1.07 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | 0.7 Change in Number of CSBMs per week | Standard Deviation 1.79 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Complete Spontaneous Bowel Movements (CSBM) | -0.1 Change in Number of CSBMs per week | Standard Deviation 0.47 |
Secondary
Change From Baseline in Frequency of Fecal Incontinence
Weekly fecal incontinence episodes recorded in daily diary.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Fecal Incontinence | 0.3 Number of episodes per week | Standard Deviation 2.1 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Fecal Incontinence | 1.9 Number of episodes per week | Standard Deviation 4.36 |
| Matching placebo - Group A | Change From Baseline in Frequency of Fecal Incontinence | 1.1 Number of episodes per week | Standard Deviation 3.04 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Fecal Incontinence | 0.9 Number of episodes per week | Standard Deviation 2.58 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Fecal Incontinence | 2.3 Number of episodes per week | Standard Deviation 5.33 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Fecal Incontinence | 1.0 Number of episodes per week | Standard Deviation 2.73 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Fecal Incontinence | 1.3 Number of episodes per week | Standard Deviation 3.29 |
Secondary
Change From Baseline in Frequency of Large Diameter Stools
Weekly frequency of large diameter stools recorded in daily diary.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Large Diameter Stools | 0 Number of episodes per week | Standard Deviation 0.28 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Large Diameter Stools | 0 Number of episodes per week | Standard Deviation 0.48 |
| Matching placebo - Group A | Change From Baseline in Frequency of Large Diameter Stools | 0.1 Number of episodes per week | Standard Deviation 0.57 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Large Diameter Stools | 0.0 Number of episodes per week | Standard Deviation 0.61 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Large Diameter Stools | -0.1 Number of episodes per week | Standard Deviation 0.49 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Large Diameter Stools | 0.0 Number of episodes per week | Standard Deviation 0.4 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Large Diameter Stools | 0.1 Number of episodes per week | Standard Deviation 0.67 |
Secondary
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.
Time frame: Baseline to Week 4
Population: All randomized participants who received at least one dose of study drug and had both baseline and post-baseline pain frequency assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Frequency of Pain With Defecation | -0.3 Change in Episodes per week | Standard Deviation 2.64 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Frequency of Pain With Defecation | -0.8 Change in Episodes per week | Standard Deviation 2.97 |
| Matching placebo - Group A | Change From Baseline in Frequency of Pain With Defecation | -0.3 Change in Episodes per week | Standard Deviation 2.91 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Frequency of Pain With Defecation | 0.4 Change in Episodes per week | Standard Deviation 2.33 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Frequency of Pain With Defecation | -0.5 Change in Episodes per week | Standard Deviation 2.29 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Frequency of Pain With Defecation | -0.8 Change in Episodes per week | Standard Deviation 2.55 |
| Matching Placebo - Group B | Change From Baseline in Frequency of Pain With Defecation | -0.7 Change in Episodes per week | Standard Deviation 2.58 |
Secondary
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.
Time frame: Baseline to Week 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: 0.5 mg plecanatide | 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 | -3.3 Severity score (0-10 scale) | Standard Deviation 3.07 |
| Experimental: 0.5 mg plecanatide | 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 Discomfort | -3.4 Severity score (0-10 scale) | Standard Deviation 2.97 |
| Experimental: 1.0 mg plecanatide - Group A | 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 | -2.3 Severity score (0-10 scale) | Standard Deviation 2.72 |
| Experimental: 1.0 mg plecanatide - Group A | 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 Discomfort | -2.4 Severity score (0-10 scale) | Standard Deviation 2.83 |
| Matching placebo - Group A | 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 | -2.3 Severity score (0-10 scale) | Standard Deviation 2.33 |
| Matching placebo - Group A | 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 Discomfort | -2.40 Severity score (0-10 scale) | Standard Deviation 2.51 |
| Experimental: 1.0 mg plecanatide - Group B | 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 | -2.2 Severity score (0-10 scale) | Standard Deviation 2.37 |
| Experimental: 1.0 mg plecanatide - Group B | 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 Discomfort | -1.9 Severity score (0-10 scale) | Standard Deviation 2.58 |
| Experimental: 2.0 mg plecanatide | 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 | -2.8 Severity score (0-10 scale) | Standard Deviation 2.19 |
| Experimental: 2.0 mg plecanatide | 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 Discomfort | -3.0 Severity score (0-10 scale) | Standard Deviation 2.23 |
| Experimental: 3.0 mg plecanatide | 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 | -2.56 Severity score (0-10 scale) | Standard Deviation 2.27 |
| Experimental: 3.0 mg plecanatide | 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 Discomfort | -2.5 Severity score (0-10 scale) | Standard Deviation 2.36 |
| Matching Placebo - Group B | 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 | -2 Severity score (0-10 scale) | Standard Deviation 2.36 |
| Matching Placebo - Group B | 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 Discomfort | -2.0 Severity score (0-10 scale) | Standard Deviation 2.46 |
Secondary
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.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Severity of Defecation Pain | -2.4 Severity Score 0-10 scale | Standard Deviation 3.13 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Severity of Defecation Pain | -2.6 Severity Score 0-10 scale | Standard Deviation 3.16 |
| Matching placebo - Group A | Change From Baseline in Severity of Defecation Pain | -2.6 Severity Score 0-10 scale | Standard Deviation 3.62 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Severity of Defecation Pain | -2.3 Severity Score 0-10 scale | Standard Deviation 2.98 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Severity of Defecation Pain | -2.5 Severity Score 0-10 scale | Standard Deviation 2.17 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Severity of Defecation Pain | -1.8 Severity Score 0-10 scale | Standard Deviation 2.7 |
| Matching Placebo - Group B | Change From Baseline in Severity of Defecation Pain | -1.6 Severity Score 0-10 scale | Standard Deviation 2.83 |
Secondary
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).
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 1.2 Score (BSFS or mBSFS-C) | Standard Deviation 1.12 |
| Experimental: 1.0 mg plecanatide - Group A | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 0.8 Score (BSFS or mBSFS-C) | Standard Deviation 1.18 |
| Matching placebo - Group A | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 1.2 Score (BSFS or mBSFS-C) | Standard Deviation 0.72 |
| Experimental: 1.0 mg plecanatide - Group B | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 1.1 Score (BSFS or mBSFS-C) | Standard Deviation 1.24 |
| Experimental: 2.0 mg plecanatide | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 1.4 Score (BSFS or mBSFS-C) | Standard Deviation 1.5 |
| Experimental: 3.0 mg plecanatide | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 1.9 Score (BSFS or mBSFS-C) | Standard Deviation 1.35 |
| Matching Placebo - Group B | Change From Baseline in Stool Consistency (Based on Bristol Stool Form Scale, BSFS or Modified Bristol Stool Form Scale for Children, mBSFS-C) | 0.7 Score (BSFS or mBSFS-C) | Standard Deviation 0.96 |
Secondary
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.
Time frame: Day 1 to first BM during Treatment Period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: 0.5 mg plecanatide | Time to First Bowl Movement (in Days) | 4.1 Days |
| Experimental: 1.0 mg plecanatide - Group A | Time to First Bowl Movement (in Days) | 2.58 Days |
| Matching placebo - Group A | Time to First Bowl Movement (in Days) | 5.35 Days |
| Experimental: 1.0 mg plecanatide - Group B | Time to First Bowl Movement (in Days) | 1.68 Days |
| Experimental: 2.0 mg plecanatide | Time to First Bowl Movement (in Days) | 2.05 Days |
| Experimental: 3.0 mg plecanatide | Time to First Bowl Movement (in Days) | 2.57 Days |
| Matching Placebo - Group B | Time to First Bowl Movement (in Days) | 2.69 Days |
Secondary
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.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: 0.5 mg plecanatide | Use of Rescue Medication | 1.3 Number of Tablets | Standard Deviation 3.6 |
| Experimental: 1.0 mg plecanatide - Group A | Use of Rescue Medication | 0.7 Number of Tablets | Standard Deviation 3.22 |
| Matching placebo - Group A | Use of Rescue Medication | 0.4 Number of Tablets | Standard Deviation 1.18 |
| Experimental: 1.0 mg plecanatide - Group B | Use of Rescue Medication | 2.4 Number of Tablets | Standard Deviation 8.73 |
| Experimental: 2.0 mg plecanatide | Use of Rescue Medication | 0.2 Number of Tablets | Standard Deviation 0.59 |
| Experimental: 3.0 mg plecanatide | Use of Rescue Medication | 1.6 Number of Tablets | Standard Deviation 5.02 |
| Matching Placebo - Group B | Use of Rescue Medication | 2.4 Number of Tablets | Standard Deviation 6.68 |