A Phase II, Multicentre, Randomised, Double-blind, Placebo Controlled, Proof of Concept Study of Efficacy and Safety of Rifamycin SV-MMX® 600 mg Tablets Administered Three or Two Times Daily to Patients With Diarrhoea-predominant Irritable Bowel Syndrome (IBS-D)
Overview
- Phase
- Phase 2
- Intervention
- Rifamycin SV 600mg t.i.d.
- Conditions
- Diarrhea-predominant Irritable Bowel Syndrome
- Sponsor
- Cosmo Technologies Ltd
- Enrollment
- 279
- Locations
- 29
- Primary Endpoint
- Proportion of subjects with relief from abdominal pain and improved stool consistency.
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The objective of this study is to evaluate the safety and efficacy Rifamycin SV-MMX® 600 mg tablets for patients with diarrhoea-predominant irritable bowel syndrome when administered two to three times daily.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed Consent: signed written informed consent before inclusion in the study
- •Sex and Age: males/females, ≥18 year old
- •IBS Diagnosis: confirmed IBS-D diagnosis per Rome IV criteria
- •Symptoms: active symptoms of IBS at baseline (day 1) as measured by average daily scores for at least 7 days before baseline:
- •abdominal pain score ≥3 using an 11-point numeric rating scale and
- •bloating score: 2-4 inclusive and
- •stool consistency: score 6 or 7 (measured by the Bristol stool form scale) for at least 2 days from day -7 to day -1
- •and by a negative response to the global IBS symptom assessment question and to the IBS-related bloating assessment question both given weekly during the screening phase up to day 1 before randomisation:
- •"In the past 7 days, have you had adequate relief of your IBS symptoms?" \[No\] and
- •"In the past 7 days, have you had adequate relief of your IBS symptom of bloating?"\[No\]
Exclusion Criteria
- •IBS: symptoms of constipation at baseline:
- •less than 3 bowel movements a week and
- •stool consistency score ≤2 for ≥2 days in a week
- •Screening phase: failure to record the daily symptom assessments in the diary cards for at least 7 days before baseline
- •Gastroenteric: underlying gastrointestinal diseases including ulcerative colitis, Crohn's disease, pancreatitis, any active infectious, haemorrhagic or inflammatory disorder not related to IBS-D, gastrointestinal motility disorders such as ileus, gastroparesis or pseudoobstruction, gastroduodenal ulcer, gastrointestinal malignancy or potentially fatal diseases if not full in remission (5 years from diagnosis and without maintenance treatment), amyloidosis and cholelithiasis if cholecystectomy not performed
- •Intolerance: ascertained underlying lactose intolerance with response to diet or any other malabsorption syndrome with the exclusion of asymptomatic lactose malabsorption
- •Coeliac disease: ascertained or presumptive underlying coeliac disease
- •Bile: ascertained or presumptive bile acid malabsorption or bile acid induced diarrhoea
- •Diabetes: underlying diabetes type I or II
- •Thyroid: abnormal thyroid function not controlled by thyroid medications
Arms & Interventions
Treatment group 1: dose regimen 1
Rifamycin SV-MMX® 600 mg modified release tablets, three times daily (t.i.d.)
Intervention: Rifamycin SV 600mg t.i.d.
Treatment group 2: dose regimen 2
Rifamycin SV-MMX® 600 mg modified release tablets, two times daily (b.i.d.) + matching placebo daily (q.d.)
Intervention: Rifamycin SV b.i.d. + Placebo
Treatment group 3: matching placebo
Rifamycin SV-MMX® matching placebo tablets, t.i.d.
Intervention: Placebo t.i.d.
Outcomes
Primary Outcomes
Proportion of subjects with relief from abdominal pain and improved stool consistency.
Time Frame: 88 days
Proportion of weekly responders defined as subjects who weekly have relief of the composite of abdominal pain and stool consistency, on the basis of their daily assessments. Relief of abdominal pain is defined as a decrease in the weekly average of abdominal pain score of at least 30% compared with baseline and relief of stool consistency is defined as a 50% or greater reduction in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. All participants will complete daily assessments of abdominal pain and stool consistency: * Abdominal Pain: Scored between 0 (no pain) and 10 (as bad as it could be) * Stool Consistency: Bristol Stool Scale (Scored 1-7)
Secondary Outcomes
- Proportion of subjects with monthly relief of global IBS symptoms [Efficacy](88 days)
- Proportion of subjects with relief of IBS-related bloating during weeks 3-12 [Efficacy](10 weeks)
- Proportion of subjects with monthly relief of IBS-related bloating [Efficacy](88 days)
- Proportion of subjects with weekly relief of IBS symptoms, bloating and abdominal pain [Efficacy](88 days)
- Number of weeks of IBS-symptom relief during follow-up [Efficacy](10 weeks)
- Number of weeks of bloating relief during follow-up [Efficacy](10 weeks)
- Change in IBS-symptoms, bloating and abdominal pain from baseline to 12 weeks - captured by a daily diary [Efficacy](12 weeks)
- Proportion of subjects with relief of global IBS symptoms during weeks 3-12 [Efficacy](10 weeks)
- Proportion of monthly responders for IBS-symptoms, bloating and abdominal pain [Efficacy](3 months)
- Change from baseline to each week during follow up for IBS-symptoms bloating, abdominal pain, stool consistency, urgency - captured by a daily diary [Efficacy](12 weeks)
- Change from baseline at weeks 4, 8 and 12 in quality of life assessment [Efficacy](12 weeks)