Irritable Bowel Syndrome Characterized by Constipation
Conditions
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.
Interventions
DRUGPlecanatide
DRUGPlacebo
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
| 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 |
| 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 |
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Matching Placebo Placebo tablets dosed once daily for 12 weeks | 354 |
| 3.0 mg Plecanatide Plecanatide 3.0 mg tablets dosed once daily for 12 weeks | 351 |
| 6.0 mg Plecanatide Plecanatide 6.0 mg tablets dosed once daily for 12 weeks | 349 |
| Total | 1,054 |
Baseline characteristics
| Characteristic | Matching Placebo | 3.0 mg Plecanatide | 6.0 mg Plecanatide | Total |
|---|---|---|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 13.71 | 43.0 years STANDARD_DEVIATION 13.76 | 43.2 years STANDARD_DEVIATION 13.34 | 43.1 years STANDARD_DEVIATION 13.6 |
| Sex: Female, Male Female | 272 Participants | 267 Participants | 266 Participants | 805 Participants |
| Sex: Female, Male Male | 82 Participants | 84 Participants | 83 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 354 | 0 / 351 | 2 / 347 |
| other Total, other adverse events | 16 / 354 | 37 / 351 | 28 / 347 |
| serious Total, serious adverse events | 5 / 354 | 4 / 351 | 2 / 347 |
Outcome results
Primary
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 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.
Time frame: 12 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Matching Placebo | Number of Abdominal Pain Responders for at Least 6 of 12 Treatment Weeks | 112 Participants |
| 3.0 mg Plecanatide | Number of Abdominal Pain Responders for at Least 6 of 12 Treatment Weeks | 145 Participants |
| 6.0 mg Plecanatide | Number of Abdominal Pain Responders for at Least 6 of 12 Treatment Weeks | 156 Participants |
Primary
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 one complete spontaneous bowel movement in the same week) for at least 6 of the 12 treatment weeks.
Time frame: 12 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Matching Placebo | Number of Overall Responders - ITT Population | 63 Participants |
| 3.0 mg Plecanatide | Number of Overall Responders - ITT Population | 106 Participants |
| 6.0 mg Plecanatide | Number of Overall Responders - ITT Population | 103 Participants |
Primary
Number of Stool Frequency Responder for at Least 6 of the 12 Treatment 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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Matching Placebo | Number of Stool Frequency Responder for at Least 6 of the 12 Treatment Weeks | 124 Participants |
| 3.0 mg Plecanatide | Number of Stool Frequency Responder for at Least 6 of the 12 Treatment Weeks | 169 Participants |
| 6.0 mg Plecanatide | Number of Stool Frequency Responder for at Least 6 of the 12 Treatment Weeks | 157 Participants |
Secondary
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 (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.
Time frame: Baseline and 12-Week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Abdominal Pain | Baseline | 6.10 score on a scale | Standard Deviation 1.793 |
| Matching Placebo | Change From Baseline in Abdominal Pain | Week 12 change from baseline | -1.79 score on a scale | Standard Deviation 2.196 |
| 3.0 mg Plecanatide | Change From Baseline in Abdominal Pain | Baseline | 5.94 score on a scale | Standard Deviation 1.704 |
| 3.0 mg Plecanatide | Change From Baseline in Abdominal Pain | Week 12 change from baseline | -2.11 score on a scale | Standard Deviation 2.215 |
| 6.0 mg Plecanatide | Change From Baseline in Abdominal Pain | Week 12 change from baseline | -2.46 score on a scale | Standard Deviation 2.37 |
| 6.0 mg Plecanatide | Change From Baseline in Abdominal Pain | Baseline | 5.95 score on a scale | Standard Deviation 1.76 |
Secondary
Change From Baseline in CSBM Frequency Rate
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.
Time frame: Baseline and 12-Week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in CSBM Frequency Rate | Baseline | 0.23 CSBMs per week | Standard Deviation 0.44 |
| Matching Placebo | Change From Baseline in CSBM Frequency Rate | Week 12 change from baseline | 0.86 CSBMs per week | Standard Deviation 1.904 |
| 3.0 mg Plecanatide | Change From Baseline in CSBM Frequency Rate | Baseline | 0.22 CSBMs per week | Standard Deviation 0.465 |
| 3.0 mg Plecanatide | Change From Baseline in CSBM Frequency Rate | Week 12 change from baseline | 1.46 CSBMs per week | Standard Deviation 2.565 |
| 6.0 mg Plecanatide | Change From Baseline in CSBM Frequency Rate | Baseline | 0.28 CSBMs per week | Standard Deviation 0.527 |
| 6.0 mg Plecanatide | Change From Baseline in CSBM Frequency Rate | Week 12 change from baseline | 1.41 CSBMs per week | Standard Deviation 2.586 |
Secondary
Change From Baseline in Stool Consistency
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
Time frame: Baseline and 12-Week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Stool Consistency | Baseline | 2.06 score on a scale | Standard Deviation 1.012 |
| Matching Placebo | Change From Baseline in Stool Consistency | Week 12 change from baseline | 1.06 score on a scale | Standard Deviation 1.357 |
| 3.0 mg Plecanatide | Change From Baseline in Stool Consistency | Baseline | 2.02 score on a scale | Standard Deviation 0.918 |
| 3.0 mg Plecanatide | Change From Baseline in Stool Consistency | Week 12 change from baseline | 1.59 score on a scale | Standard Deviation 1.592 |
| 6.0 mg Plecanatide | Change From Baseline in Stool Consistency | Baseline | 1.98 score on a scale | Standard Deviation 0.913 |
| 6.0 mg Plecanatide | Change From Baseline in Stool Consistency | Week 12 change from baseline | 1.86 score on a scale | Standard Deviation 1.593 |
Secondary
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).
Time frame: Baseline and 12-week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Straining | Baseline | 6.39 score on a scale | Standard Deviation 1.991 |
| Matching Placebo | Change From Baseline in Straining | Week 12 change from baseline | -1.87 score on a scale | Standard Deviation 2.464 |
| 3.0 mg Plecanatide | Change From Baseline in Straining | Baseline | 6.47 score on a scale | Standard Deviation 1.828 |
| 3.0 mg Plecanatide | Change From Baseline in Straining | Week 12 change from baseline | -2.69 score on a scale | Standard Deviation 2.422 |
| 6.0 mg Plecanatide | Change From Baseline in Straining | Baseline | 6.50 score on a scale | Standard Deviation 1.822 |
| 6.0 mg Plecanatide | Change From Baseline in Straining | Week 12 change from baseline | -2.88 score on a scale | Standard Deviation 2.464 |
Secondary
Number of Patients With a SBM Within 24 Hours After the First Dose
Number of patients with a SBM (spontaneous bowel movement) within 24 hours after the first dose of study drug
Time frame: Up to 24 hours after first dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Matching Placebo | Number of Patients With a SBM Within 24 Hours After the First Dose | 118 Participants |
| 3.0 mg Plecanatide | Number of Patients With a SBM Within 24 Hours After the First Dose | 168 Participants |
| 6.0 mg Plecanatide | Number of Patients With a SBM Within 24 Hours After the First Dose | 175 Participants |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Matching Placebo | Number of Sustained Efficacy Responders | 61 Participants |
| 3.0 mg Plecanatide | Number of Sustained Efficacy Responders | 99 Participants |
| 6.0 mg Plecanatide | Number of Sustained Efficacy Responders | 96 Participants |