Irritable Bowel Syndrome With Diarrhea
Conditions
Keywords
IBS, IBS-D, IBS with diarrhea, Diarrhea, Irritable bowel syndrome with diarrhea
Brief summary
This study will evaluate the effectiveness and safety of repeat treatment with rifaximin 550 mg three times a day in patients with IBS with diarrhea who respond to initial treatment of rifaximin 550 mg three times a day.
Detailed description
It is important in chronic conditions to have information about how a product that is intended for short course administration in order to confer prolonged benefit should be administered beyond the first cycle of use once symptoms reappear. This Phase 3 study will evaluate the efficacy and safety of repeat treatment with rifaximin 550 mg three times daily (TID) for 14 days in subjects with IBS-D who respond to an initial treatment course with rifaximin 550 mg TID for 14 days. This study consists of several treatment phases outlined below: Screening/Treatment 1 Phase. Subjects will receive single-blind placebo TID for 7-13 days and answer daily IBS symptom-related questions. Treatment 2 Phase. Eligible subjects will receive open-label rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up. Responders will continue into Maintenance Phase 1. Nonresponders will withdraw from the study. Maintenance Phase 1. Subjects will continue the treatment-free follow-up period for up to 18 weeks until either: 1) they experience recurrence or 2) enrollment is met in the Treatment 3 Phase (Double Blind Repeat Treatment Phase). Subjects who do not meet recurrence criteria by the end of the Maintenance Phase 1 will withdraw from the study. Treatment 3 Phase/ Double Blind Repeat Treatment Phase. Subjects who meet criteria for recurrence will be randomized 1:1 to receive either rifaximin 550 mg TID or placebo TID for 2 weeks with a 4-week treatment-free follow-up. Primary efficacy analysis will be performed at the end of the Treatment 3 Phase (at Week 6 of the double-blind period). Maintenance Phase 2. All subjects continued into an additional treatment-free follow-up period of up to 6 weeks (Maintenance Phase 2). Treatment 4 Phase/Second Repeat Treatment Phase. Subjects will receive the same double-blind treatment as previously assigned in the Treatment 3 Phase for 2 weeks with a 4-week treatment-free follow-up. A lactulose breath test sub-study will be conducted at select sites.
Interventions
DRUGopen-label rifaximin
550 mg three times a day (open-label)
3 times a day (double-blind)
DRUGdouble-blind rifaximin
550 mg three times a day (double-blind)
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* IBS confirmed by Rome III diagnostic criteria. * At least 18 years of age. * Colonoscopy within the past 10 years to rule out inflammatory bowel disease; or flexible sigmoidoscopy if \< 50 years of age or previous colonoscopy \> 10 years prior. * Willing to maintain a stable diet. including vitamins, supplements, and nutraceuticals.
Exclusion criteria
* Diabetes (Type 1 or 2). * Lactose intolerance and not controlled by a lactose-free diet. * Pregnant or planning to become pregnant or is lactating. * History of HIV or hepatitis B or C. * Participation in investigational study within past 30 days. * Taking rifaximin or any other antibiotic within past 60 days. * Unstable cardiovascular or pulmonary disease, with change in treatment in last 30 days due to worsening disease condition. * History of GI surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Repeat Treatment Responders | 4-week treatment-free follow-up in double-blind repeat treatment phase. | Subjects who respond to repeat treatment in both IBS-related abdominal pain and stool consistency. The proportion of patients who responded to repeat treatment during the first double-blind repeat treatment phase is presented. Response is defined as improvement from baseline in abdominal pain AND reduction from baseline in diarrhea. |
Countries
Germany, United Kingdom, United States
Participant flow
Pre-assignment details
The screening phase included a 10 (±3) day run-in treatment period, during which subjects received single-blind placebo and completed a daily IBS symptom diary. Subjects who had active symptoms of IBS with diarrhea, and satisfied other entry criteria, entered the open-label period of study.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Rifaximin Only The 1943 subjects in this group did not continue into the double-blind period of the study. Open-label treatment was rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up. | 1,943 |
| Double-blind Rifaximin (Retreatment) The 328 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the rifaximin group for the double-blind retreatment period. | 328 |
| Double-blind Placebo (Retreatment) The 308 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the placebo group for the double-blind retreatment period. | 308 |
| Total | 2,579 |
Baseline characteristics
| Characteristic | Open-label Rifaximin Only | Double-blind Rifaximin (Retreatment) | Double-blind Placebo (Retreatment) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 0 Participants | 1 Participants | 9 Participants |
| Age, Categorical >=65 years | 172 Participants | 39 Participants | 29 Participants | 240 Participants |
| Age, Categorical Between 18 and 65 years | 1763 Participants | 289 Participants | 278 Participants | 2330 Participants |
| Age, Continuous | 46.3 years STANDARD_DEVIATION 13.5 | 47.9 years STANDARD_DEVIATION 14.2 | 45.6 years STANDARD_DEVIATION 13.8 | 46.4 years STANDARD_DEVIATION 13.7 |
| Sex: Female, Male Female | 1319 Participants | 222 Participants | 219 Participants | 1760 Participants |
| Sex: Female, Male Male | 624 Participants | 106 Participants | 89 Participants | 819 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 | 198 / 2,579 | 74 / 328 | 69 / 308 |
| serious Total, serious adverse events | 28 / 2,579 | 4 / 328 | 4 / 308 |
Outcome results
Primary
Repeat Treatment Responders
Subjects who respond to repeat treatment in both IBS-related abdominal pain and stool consistency. The proportion of patients who responded to repeat treatment during the first double-blind repeat treatment phase is presented. Response is defined as improvement from baseline in abdominal pain AND reduction from baseline in diarrhea.
Time frame: 4-week treatment-free follow-up in double-blind repeat treatment phase.
Population: Intent-to-treat population, defined as patients who received ≥ 1 dose of study drug in the double-blind period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Rifaximin (Retreatment) | Repeat Treatment Responders | 32.6 percentage of patients |
| Double-blind Placebo (Retreatment) | Repeat Treatment Responders | 25.0 percentage of patients |
Comparison: A worst case analysis was performed, in which patients with \< 4 days of IBS symptom data in a given week were considered as non-responders for that week.p-value: 0.0232Cochran-Mantel-Haenszel