A Four Arm Study to Evaluate the Safety and Efficacy of 3 Different Doses of RVX-100 Versus Placebo in Subjects With Irritable Bowel Syndrome Accompanied by Diarrhea (IBS-D)

Study Overview
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Brief Summary
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The purpose of this study is to determine if RVX-100 is safe and effective in treating acute abdominal pain in patients with irritable bowel syndrome accompanied by diarrhea.

Official Title
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A Phase 2, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Four-Arm Trial to Evaluate the Safety and Efficacy of 3 Different Doses of RVX-100 Versus Placebo for the Treatment of Abdominal Pain in Patients With Irritable Bowel Syndrome Accompanied by Diarrhea (IBS-D)

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: 0.075 mg RVX-100
* Drug: 0.125 mg RVX-100
* Drug: 0.250 mg RVX-100
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Adult male or female, aged ≥18 and ≤75 years old. Subject/ legal representative is able to understand and sign informed consent form. Have abdominal pain severity defined as weekly average of worst abdominal pain in past 24 hours score of ≥ 3.0 on a 0 to 10 point scale during the second week of the Baseline phase. Have IBS-D according to Rome III criteria and ≥25% of stools on the BSS inclusion criteria rated as 6 or 7 during the Baseline phase. Not pregnant, lactating, or breastfeeding. If a female of childbearing potential, the subject must agree to remain abstinent or practice two medically acceptable forms of contraception during the screening, baseline, treatment, and withdrawal periods. Acceptable forms of contraception include oral contraception, intrauterine devices, implantable devices, and barrier methods. If a barrier method is chosen, a double barrier is required. Discontinue all medications used to treat IBS symptoms (prescription and non-prescription) and prescription analgesics at least two (2) weeks prior to the start of the baseline period until after the final study visit. (Final study visit occurs two (2) weeks after the last dose of study medication.) Acetaminophen may be used as a rescue medication as long as it is carefully documented on the Case Report Form (CRF). Fiber supplements are permitted if they are taken at the same frequency and amount throughout the study and were taken during the four (4) weeks prior to the Baseline phase. This must be documented in the source document file and the CRF. Willing and able to comply with all study-related procedures, including not incorporating significant changes in diet. Exclusion Criteria: Positive for fecal ova and parasites (O&P) or Clostridium difficile (ELISA) or other bacterial pathogens (standard stool culture) during the Screening phase. Taking medication for the treatment of IBS during the baseline phase (other than acetaminophen). Taking any treatment for IBS including any of the following classes of medications within 2 weeks prior to baseline visit (Visit 2), or at any point during the study: Antispasmodic or anticholinergic agents Combination products including atropine, hyoscyamine, phenobarbital, and/or scopolamine Antidepressants (such as monoamine oxidase inhibitors [MAOI], selective serotonin reuptake inhibitors [SSRIs], and tricyclic antidepressants), to include, but not limited to the following: Combination products including pheniramine, phenyltoloxamine, or pyrilamine Laxatives Opioids/narcotic analgesics Phenothiazines antipsychotics and anti-emetics History of anticholinergic psychosis (psychosis associated with exposure to anticholinergic medications). Laboratory values greater than three times the upper limit of normal (ULN) alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT). Laboratory values greater than two times the ULN for total bilirubin (TBil), creatinine (sCr) or blood urea nitrogen (BUN). Active infection with hepatitis (A, B, or C) or positive confirmatory test for HIV1, or HIV2 (results of the HIV testing will be kept strictly confidential. Subject may wish to undergo HIV testing as per the guidelines for HIV testing requirements in India pursuant to NACO). History of allergic reaction to l-hyoscyamine or atropine, or any component in the formulation of the study drugs. Evidence of disease (based on medical history) that could adversely affect the subject's safety during participation in this study or interfere with the interpretation of study results, including but not limited to: glaucoma; pyloric stenosis; clinically significant benign prostatic hypertrophy; clinically significant heart or lung or disease; active peptic ulcer; celiac disease; digestive tract obstruction or paralysis; myasthenia gravis; inflammatory bowel disease; poorly controlled hypertension; hyperthyroidism; decreased hepatic or renal function; urinary retention, or lactose intolerance. Use of any investigational drug within 30 days prior to the Baseline Visit (Visit 2), or anytime during study. History of non-compliance with treatment or clinical visit attendance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group taking 0.075 mg RVX-100<br>This group is taking 0.075 mg RVX-100 | Drug: 0.075 mg RVX-100<br>* This group is taking the lowest dose of RVX-100<br>|
| Active Comparator: Group taking 0.125 mg RVX-100<br>This group is taking 0.125 mg RVX-100 | Drug: 0.125 mg RVX-100<br>* This group is taking an average dose of RVX-100<br>|
| Active Comparator: 0.250 mg RVX-100<br>This group is taking 0.250 mg RVX-100 | Drug: 0.250 mg RVX-100<br>* This group is taking the highest dose of RVX-100<br>|
| Placebo Comparator: placebo<br>This group is taking a placebo | Drug: placebo<br>* This group is taking a placebo<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weekly average abdominal pain severity score from baseline. |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weekly average Abdominal Pain Severity score from baseline to week 8 |  | 8 weeks | 
| Time to response, based on abdominal pain severity scores. |  | 8 weeks | 
| Proportion of subjects in each treatment arm who are weekly responders. |  | 8 weeks | 
| Proportion of subjects in each treatment arm who are end-of-treatment responders |  | 8 weeks | 
| Number of pain-free days per week, based on responses to the Abdominal Pain Severity scale |  | 8 weeks | 
| Bowel urgency |  | 8 weeks | 
| Stool consistency |  | 8 weeks | 
| Stool frequency |  | 8 weeks | 
| Fecal incontinence |  | 8 weeks | 
| Bloating |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abdominal pain, bloating, diarrhea, irritable bowel