This study is being conducted to evaluate the safety and effectiveness of RNIB21 in adults with IBS-D. Researchers want to determine whether adding an agent that breaks down mucus to the FDA-approved medication rifaximin may improve symptom relief compared to a placebo.

You may be eligible for this study if you meet the following criteria.

Inclusion Criteria:

• Diagnosed with Irritable Bowel Syndrome (IBS) with diarrhea
• Received a colonoscopy within the past 3 years
• No current asthma
• No current diabetes
• No history of Clostridium difficile infection
• No history of GI surgeries (except appendectomy and cholecystectomy)
• No current inflammatory bowel disease
• Not pregnant
• Ages 18+

If you qualify and choose to participate, you will be asked to:

1. Complete a phone screening to determine initial eligibility.
2. Attend study visits over approximately 4 months.
3. Review and sign an informed consent form.
4. Provide information about your medical history and IBS symptoms.
5. Undergo physical examinations, vital sign measurements, blood draws, urine testing, and a lactulose breath test.
6. Complete questionnaires and daily symptom surveys.
7. Take the study medication or placebo for 2 weeks.
8. Participate in follow-up visits and phone calls so the study team can monitor your health and symptoms.

The study includes 7 visits total (5 in-person visits and 2 phone visits). Optional sub-studies are also available, including stool sample collection and additional blood sampling.

Participants may receive $325 compensation for completing all 7 study visits. Participants who choose to enroll in the optional stool sample sub-study may receive $20 per stool sample, and those who participate in the optional pharmacokinetic (PK) blood sampling sub-study may receive up to $495. Compensation is provided for completed study activities.

There is no cost for you to participate in our research study.