A Study to Assess Repeat Treatment Efficacy and Safety of Rifaximin 550 mg TID in Subjects with Irritable Bowel Syndrome with Diarrhoea (IBS-D)
- Conditions
- Irritable bowel syndrome (IBS) is a heterogeneous gastrointestinal (GI) disorder characterized by frequent and debilitating symptoms (e.g. diarrhoea, bloating, abdominal pain, urgency to defecate, gas, faecal incontinence). A distinct feature of the disorder is the often cyclical waxing and waning of various symptoms. There remains a significant unmet need for effective and safe therapies, particularly for IBS with diarrhoea (IBS-D).MedDRA version: 16.0 Level: LLT Classification code 10060849 Term: Diarrhoea predominant irritable bowel syndrome System Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2013-002394-22-GB
- Lead Sponsor
- Salix Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 800
1. Subject is 18 years of age
2. Male or female
Females of childbearing (reproductive) potential must have a negative pregnancy test at Screening/Treatment 1 Phase and agree to use an acceptable method of contraception throughout their participation in the study. Acceptable methods of contraception include double barrier methods (condom with spermicidal jelly or a diaphragm with spermicide), hormonal methods (e. g. oral contraceptives, patches or medroxyprogesterone acetate), or an intrauterine device (IUD) with a documented failure rate of less than 1% per year.
Abstinence or partner(s) with a vasectomy may be considered an acceptable method of
contraception at the discretion of the investigator.
Females who have been surgically sterilized (e.g, hysterectomy or bilateral tubal ligation) or who are postmenopausal (total cessation of menses for > 1 year) will not be considered females of childbearing potential”.
3. Subject has IBS confirmed by the Rome III diagnostic criteria3 (below):
Recurrent abdominal pain or discomfort** at least 3 days per month in the last 3 months, with symptom onset at least 6 months prior to diagnosis associated with 2 or more of the following:
?? Improvement with defecation;
?? Onset associated with a change in frequency of stool;
?? Onset associated with a change in form (appearance) of stool
**Discomfort means an uncomfortable sensation not described as pain.
4. During the Screening/Treatment 1 Phase (at least 7 and up to 13 days), the following
average daily symptom scores for IBS are required in all categories for entry into the study:
?? An average score of greater than or equal to 3 for abdominal pain
?? An average score of greater than or equal to 3 for bloating
?? At least 2 days in a week with stool consistency of 6 (Fluffy pieces with ragged edges, a mushy stool) or 7 (Watery stool, no solid pieces; entirely liquid) using the BSS
5. Subject may be included if they have had a documented colonoscopy within the past
10 years (preferably including biopsies) as part of a workup for IBS-D. Subjects with a
clinical diagnosis of IBS-D who are either (1) less than 50 years of age and have never had a colonoscopy or (2) whose last colonoscopy was greater than 10 years ago may be possible etiologies of the diarrhoea such as microscopic colitis and in the opinion of the investigator, the subject does not need a complete colonoscopy for other medical reasons.
6. Subject must maintain a stable diet; including dietary supplements, vitamins and other nutraceuticals. Subject should not introduce any major lifestyle changes for the duration of the study (eg.: initiation or discontinuation of a high fibre or low carbohydrate diet)
7. Subject is capable of understanding the requirements of the study, is willing to comply with all study procedures, understands the language of the informed consent form, and is capable and willing to sign the informed consent form.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subje
A subject will be eligible for inclusion in this study if he/she meets any of the following
criteria:
1. Presents with Type 1 = Separate hard lumps, like nuts (hard to pass) or Type 2 = Sausage-shaped but lumpy (on the BSS) during the Screening/Treatment 1 Phase (for entry into Treatment 2 Phase)
2. Subject has failed to record 7 days of the daily diary assessments during the
Screening/Treatment 1 Phase (for entry into Treatment 2 Phase)
3. Subject has current evidence of duodenal ulcer, gastric ulcer, diverticulitis, gastroesophageal reflux (GERD), or infectious gastroenteritis. Note: subjects with GERD controlled by stable (> 30 days) doses of medication or diet are eligible to participate in the study.
4. Subject has a history of inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis, celiac disease), GI malignancy, GI obstruction, gastroparesis, carcinoid syndrome, pancreatitis, amyloidosis, ileus or cholelithiasis. The subject is eligible to participate if they have had cholelithiasis and had a cholecystectomy greater than 6 months prior to signing the ICF.
5. Subject has diabetes (Type 1 or Type 2)
6. Subject requires GI surgery, has a history of GI surgery, or has had a polypectomy (open surgical or endoscopic) for which the histology showed it to be malignant. Subjects are excluded if they have had a cholecystectomy and/or abdominal hernia repair less than 6 months prior to signing the ICF. The subject is eligible to participate if they have had: a routine endoscopic
polypectomy with benign histology, and/or an uncomplicated appendectomy with no
history of post operative obstruction or symptomatic adhesions for at least 5 years prior to signing the ICF.
7. Subject has lactose intolerance not controlled by a lactose free diet.
8. Subject presents with symptoms of enteric infections including but not limited to Yersinia enterocolitica, Campylobacter jejuni, Salmonella, Shigella, ovum and parasites, and/or Clostridium difficile.
9. Subject has history of a major psychiatric disorder (DSM-III-R or DSM-IV), including
major depression, psychoses, alcohol or substance abuse within the past 24 months prior to signing the informed consent
10. Subject has a history of seizure disorders
11. Subject is pregnant, planning to become pregnant, or is lactating
12. Subject has a history of human immunodeficiency virus (HIV) or hepatitis (B or C)
13. Subject has a history of abnormal thyroid function not controlled by thyroid medications
14. Subject has hepatic disease manifested by twice the upper limit of normal (ULN) for any of the following liver function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin (except in isolated elevation of unconjugated bilirubin)
15. Subject has renal disease manifested by 1.5 times the ULN of serum creatinine or blood urea nitrogen levels
16. Exclusion criteria #16 removed during Amendment 2
17. Subject has unstable cardiovascular or pulmonary disease, categorized by a worsening in the disease condition that requires a change in treatment or medical care within
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of repeat treatment with rifaximin 550mg TID in subjects with IBS-D who responded to initial treatment with rifaximin 550 mg TID.;Secondary Objective: To evaluate the safety of rifaximin 550 TID in subjects with IBS-D.;<br> Primary end point(s): Efficacy Endpoint:<br> Proportion of subjects who are responders to repeat treatment in both IBS-related abdominal pain AND stool consistency during the 4 week treatment-free follow-up (or Primary Evaluation Period [PEP]) in the Double Blind Repeat (DBR) Treatment Phase.<br> <br> ;Timepoint(s) of evaluation of this end point: Weeks 2 to 6 of the 4 week follow up of Treatment 2 Phase
- Secondary Outcome Measures
Name Time Method