Irritable Bowel Syndrome With Diarrhea
Conditions
Keywords
IBS, Diarrhea, IBS-D, Irritable Bowel Syndrome, Abdominal pain, Bloating
Brief summary
The purpose of this study is to determine the daily dose of mesalamine granules that will provide adequate relief from symptoms of IBS with diarrhea.
Interventions
DRUGPlacebo
placebo capsules once daily for 12 weeks
DRUGMesalamine Granules 750 mg
750 mg mesalamine granules once daily for 12 weeks
DRUGMesalamine Granules 1500 mg
1500 mg mesalamine granules once daily for 12 weeks
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 No maximum
Healthy volunteers
No
Inclusion criteria
Male or non-pregnant, non-lactating female subjects Diagnosed with IBS confirmed by the Rome III criteria Meet the following IBS symptom scores in all categories during the diary eligibility period: * An average daily score of greater than or equal to 3 for abdominal pain * An average daily score of greater than or equal to 3 for bloating * An average daily score of 5 or greater for stool consistency using the Bristol Stool Scale * Does not have adequate relief of IBS symptoms (weekly reported) over the past 7 days on the first day of screening and on the day of randomization
Exclusion criteria
* Present with hard or lumpy stools (Type 1 or Type 2) on the Bristol Stool form Scale during the diary eligibility period * history of inflammatory bowel disease * has Type 1 or 2 diabetes * pregnant or lactating * history of HIV or hepatitis B or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 3 months | A weekly responder in abdominal pain is defined as a ≥30% improvement from baseline in the weekly average abdominal pain score on a 10-point scale (0=no pain - 10= worst possible pain). A weekly responder in stool consistency is defined as ≥50% reduction in the number of days in a week with stool consistency of Type 6 or 7 compared with baseline using the Bristol Stool Scale. Monthly responders are subjects who are weekly responders in both abdominal pain and stool consistency for at least two out of four weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Are Monthly Responders in Both Abdominal Pain and Stool Consistency for at Least 2 Months During the 3-month Treatment Period | 3 months | A weekly responder in abdominal pain is defined as a ≥30% improvement from baseline in the weekly average abdominal pain score on a 10-point scale (0=no pain - 10= worst possible pain). A weekly responder in stool consistency is defined as ≥50% reduction in the number of days in a week with stool consistency of Type 6 or 7 compared with baseline using the Bristol Stool Scale. Monthly responders are subjects who are weekly responders in both abdominal pain and stool consistency for at least two out of four weeks. |
Countries
United States
Participant flow
Recruitment details
Study Period: 09Aug2010 to 16Aug2011. 20 Study Sites; US Only. Study locations were a variety including: Gastrointestinal, Family Practice, Medical Centers and/or University setting
Pre-assignment details
Failure to meet baseline IBS symptom scores (based on diary responses)
Participants by arm
| Arm | Count |
|---|---|
| Mesalamine Granules 1500 mg Mesalamine Granules 1500 mg : 1500 mg mesalamine granules once daily for 12 weeks | 51 |
| Mesalamine Granules 750 mg Mesalamine Granules 750 mg : 750 mg mesalamine granules once daily for 12 weeks | 47 |
| Placebo Placebo : placebo capsules once daily for 12 weeks | 50 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 4 | 3 |
Baseline characteristics
| Characteristic | Mesalamine Granules 750 mg | Placebo | Mesalamine Granules 1500 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 6 Participants | 2 Participants | 2 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 48 Participants | 48 Participants | 137 Participants |
| Age, Continuous | 44.4 years STANDARD_DEVIATION 16 | 44.6 years STANDARD_DEVIATION 12.04 | 42.5 years STANDARD_DEVIATION 13.17 | 43.8 years STANDARD_DEVIATION 13.73 |
| Region of Enrollment United States | 47 participants | 50 participants | 51 participants | 148 participants |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 32 Participants | 92 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 19 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 51 | 9 / 47 | 7 / 50 |
| serious Total, serious adverse events | 0 / 51 | 1 / 47 | 0 / 50 |
Outcome results
Primary
The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months.
A weekly responder in abdominal pain is defined as a ≥30% improvement from baseline in the weekly average abdominal pain score on a 10-point scale (0=no pain - 10= worst possible pain). A weekly responder in stool consistency is defined as ≥50% reduction in the number of days in a week with stool consistency of Type 6 or 7 compared with baseline using the Bristol Stool Scale. Monthly responders are subjects who are weekly responders in both abdominal pain and stool consistency for at least two out of four weeks.
Time frame: 3 months
Population: Intent to Treat Population included all randomized subjects who ingested at least one dose of study drug. Analysis of study data was based on observed cases, missing data remained missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mesalamine Granules 1500 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 2 months | 13 participants |
| Mesalamine Granules 1500 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 0 month | 18 participants |
| Mesalamine Granules 1500 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 3 months | 11 participants |
| Mesalamine Granules 1500 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 1 month | 9 participants |
| Mesalamine Granules 750 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 2 months | 5 participants |
| Mesalamine Granules 750 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 1 month | 5 participants |
| Mesalamine Granules 750 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 3 months | 10 participants |
| Mesalamine Granules 750 mg | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 0 month | 27 participants |
| Placebo | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 3 months | 8 participants |
| Placebo | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 0 month | 28 participants |
| Placebo | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 1 month | 8 participants |
| Placebo | The Number of Months That Subjects Are Monthly Responders in Both IBS-related Abdominal Pain AND Stool Consistency During the Entire Three Months. | 2 months | 6 participants |
Comparison: Proportional odds model was used to compare the number of months the subjects are responders.p-value: 0.032795% CI: [1.068, 4.664]Proportional Odds Model
p-value: 0.72695% CI: [0.531, 2.483]Proportional Odds Model
Secondary
Proportion of Subjects Who Are Monthly Responders in Both Abdominal Pain and Stool Consistency for at Least 2 Months During the 3-month Treatment Period
A weekly responder in abdominal pain is defined as a ≥30% improvement from baseline in the weekly average abdominal pain score on a 10-point scale (0=no pain - 10= worst possible pain). A weekly responder in stool consistency is defined as ≥50% reduction in the number of days in a week with stool consistency of Type 6 or 7 compared with baseline using the Bristol Stool Scale. Monthly responders are subjects who are weekly responders in both abdominal pain and stool consistency for at least two out of four weeks.
Time frame: 3 months
Population: Intent to Treat Population included all randomized subjects who ingested at least one dose of study drug. Analysis of study data was based on observed cases, missing data remained missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamine Granules 1500 mg | Proportion of Subjects Who Are Monthly Responders in Both Abdominal Pain and Stool Consistency for at Least 2 Months During the 3-month Treatment Period | 24 participants |
| Mesalamine Granules 750 mg | Proportion of Subjects Who Are Monthly Responders in Both Abdominal Pain and Stool Consistency for at Least 2 Months During the 3-month Treatment Period | 15 participants |
| Placebo | Proportion of Subjects Who Are Monthly Responders in Both Abdominal Pain and Stool Consistency for at Least 2 Months During the 3-month Treatment Period | 14 participants |
p-value: 0.043295% CI: [1.027, 5.467]Regression, Logistic
p-value: 0.605995% CI: [0.515, 3.115]Regression, Logistic