Efficacy and Safety Evaluation of Saccharomyces boulardii CNCM I-745 in Non-Constipated Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-520276-10-00
- Protocol
- BoWell - Sb252
- Sponsor
- Biocodex
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the efficacy of **Saccharomyces boulardii** CNCM I-745 on global symptoms of **Irritable Bowel Syndrome** (IBS), as measured by the **Irritable Bowel Syndrome Symptom Severity Scale** (IBS-SSS), in comparison to placebo after 8 weeks. This is clinically relevant as it aims to provide evidence for a potential therapeutic option for managing symptoms in patients with non-constipated IBS, a condition that significantly impacts quality of life.
Secondary objectives include:
- Evaluating the impact of Saccharomyces boulardii CNCM I-745 on the quality of life of IBS patients compared to placebo.
- Demonstrating the efficacy of Saccharomyces boulardii CNCM I-745 on both global and individual IBS symptoms, measured by the IBS-SSS, at each time point, in comparison to placebo.
- Assessing the proportion of patients who improved by ≥ 50 points on the IBS-SSS.
- Evaluating the proportion of responders according to the European Medicines Agency (EMA) definition after 8 weeks of treatment.
- Assessing the safety profile and tolerability of Saccharomyces boulardii CNCM I-745 capsules (500 mg/day) in IBS patients compared to placebo.
Participants
The clinical trial involves participants diagnosed with **Non-constipated Irritable Bowel Syndrome (IBS)**, specifically excluding those with constipation-predominant IBS. The study population comprises both male and female subjects aged between 18 and 65 years. Participants are required to have an IBS Symptom Severity Scale (IBS-SSS) total score of 175 or higher at inclusion. The trial does not involve a vulnerable population. Participants are expected to maintain their existing nutrition habits throughout the study. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **Saccharomyces boulardii CNCM I-745** in adult patients with non-constipated **Irritable Bowel Syndrome (IBS)**. The trial aims to demonstrate the efficacy of the investigational product on global IBS symptoms, measured by the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS), in comparison to placebo after 8 weeks. The primary endpoint is the absolute change from baseline in IBS-SSS total score at 8 weeks. Secondary endpoints include changes in IBS-Quality of Life (IBS-QOL) score and IBS-SSS subscores at various time points, as well as the proportion of responders according to predefined criteria.
The trial will span an estimated duration from August 2025 to September 2026. Participants will be involved for a maximum of 12 weeks, with the study comprising several key visits. The inclusion visit, or screening, will determine eligibility based on criteria such as age, diagnosis of IBS according to Rome IV criteria, and an IBS-SSS total score of at least 175. Follow-up visits will occur at 4-week intervals to assess changes in symptoms and quality of life, with the final visit marking the end of the study at 12 weeks. Participants will be required to maintain their nutritional habits and comply with study requirements throughout the trial.
Conditions that may lead to early termination from the study include the occurrence of adverse events, serious adverse events, or any changes in vital signs and body weight that necessitate discontinuation of the study treatment. The trial will ensure that all operations related to the manufacturing and release of the investigational medicinal product are consistent with the authorized product, with minor modifications such as the use of HPMC white capsules. The study will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of **Ultra-Levura 250 mg capsules**, which contain the active substance **Saccharomyces boulardii CNCM I-745 lyophilized**. This investigational medicinal product is presented in the form of hard capsules and is administered orally. The maximum daily dose is 500 mg, with a total maximum dose of 42,000 mg over a treatment period of up to 12 weeks. The manufacturing process of the investigational product includes the use of HPMC white capsules, differing from the authorized product's white gelatin capsules, and excludes a drying step. The product is classified under the ATC code A07FA02, indicating its use in the treatment of gastrointestinal disorders.
The trial also includes a **placebo** comparator, referred to as "Placebo to Saccharomyces boulardii." This placebo is used to evaluate the efficacy of the investigational product in a double-blind manner. The placebo does not contain any active substances and is designed to match the investigational product in appearance and administration route, which is oral.
Additionally, the trial utilizes a standard-of-care treatment involving **Loperamide**, which is combined with **Dimeticone**. This combination is administered orally in a pharmaceutical form identified as PHF00245MIG. The maximum daily dose for this treatment is 8 mg, with a total maximum dose of 8 mg over the treatment period. Loperamide is classified under the ATC code A07DA03, indicating its use as an antidiarrheal agent. The inclusion of this treatment aims to provide a comprehensive assessment of the investigational product's efficacy in comparison to existing standard treatments.
Efficacy
The efficacy of Saccharomyces boulardii CNCM I-745 in adult patients with non-constipated **Irritable Bowel Syndrome** (IBS) will be assessed through a double-blind, randomized, placebo-controlled, multicenter trial. The primary endpoint for evaluating efficacy is the absolute change from baseline in the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) total score at 8 weeks (day 56). Secondary endpoints include the absolute change from baseline in the IBS-SSS total score at days 28 and 84, as well as changes in IBS-SSS subscores, which cover abdominal pain, number of days with pain, abdominal distension, satisfaction with bowel habits, and impact on life in general at days 56 and 84.
Additional secondary endpoints involve the absolute change from baseline in the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) score at days 56 and 84. The proportion of responders, defined as patients who improved by at least 50 points on the IBS-SSS at days 28, 56, and 84 compared with baseline, will also be evaluated. Furthermore, the proportion of responders at days 56 and 84 will be assessed according to the EMA definition, which includes patients with a subject's global assessment of efficacy scale (IBS-GIS) of the highest two improvement grades on a 7-point scale and an abdominal pain score improved by at least 30% compared to baseline. The abdominal pain score will be derived from the abdominal pain 11-point NRS.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female aged ≥ 18 and ≤ 65 years.
- Diagnosis of IBS of any subtype, except constipation predominant (IBS-C), according to Rome IV criteria.
- IBS-SSS total score ≥ 175 at inclusion.
- Able and willing to maintain their nutrition habits throughout the study participation.
- Able to understand and willing to comply with study requirements and to provide written informed consent.
- For women of childbearing potential: willing to use one or more acceptable birth control method throughout the study participation.
Exclusion Criteria
- Diagnosis of IBS-C according to Rome IV criteria.
- Patient with more than 5 bowel movements per day on average during the screening period, according to the patient’s diary (BSFS).
- Severe illness(es) or medical condition(s), including gastrointestinal pathologies (other than IBS): gastrointestinal ulcers, coeliac disease, inflammatory bowel disease, bowel cancer, acute or chronic diarrhea secondary to confirmed infectious gastroenteritis, or enteral or parenteral nutrition.
- History of abdominal surgery (except for appendectomy, cholecystectomy, surgery for hemorrhoids or cesarian section, more than 6 months prior to inclusion).
- Familial colorectal cancer syndrome (Lynch, Familial Adenomatous Polyposis).
- Fecal transplant within 6 months prior to screening
- Use of products marketed as prebiotics, probiotics or synbiotics within 2 weeks prior to screening. These products, with the exception of the investigational product, will not be allowed during the trial. Regular cheese or yogurt containing lactic acid bacteria are not an exclusion criterion.
- Systemic antibiotic or antimycotic treatment within 2 weeks prior to randomization. These treatments are not allowed during the study.
- Laxatives, antibloating agents, antidiarrheal medication, antispasmodics, within 2 weeks prior to screening. These treatments are not allowed during the study, except loperamide which can be used as rescue medication.
- Daily or regular non-steroidal anti-inflammatory drugs (NSAIDS) at doses above cardiovascular prophylaxis (low dose aspirin) are not allowed within 2 weeks prior to screening and throughout the study participation
- Use of opioids or narcotic analgesics, including tramadol and codeine, within 6 weeks prior to screening. These treatments are not allowed during the study.
- Treatment with two or more antidepressant/anxiolytic/antipsychotic within 3 months prior to study entry or during the trial. Treatment with a single antidepressant or anxiolytic or antipsychotic agent before and during the trial is allowed provided that the dose is stable within 3 months prior to study entry and during the trial participation
- Treatment with anticholinergics for overactive bladder such as solifenacin, darifenacin, oxybutynin, tolterodine, fesoterodin, propiverin, trospium chloride, or mirabegron, within 1 week prior to screening. These treatments are not allowed during the study.
- Allergy to yeast, especially Saccharomyces boulardii, or known hypersensitivity to one of the components.
- Patients having a central venous catheter, critically ill patients, and immunocompromised patients.
- Patients with rare hereditary problems of galactose or fructose intolerance, total lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
- Excessive alcohol consumption (>7 units/week) and/or drug abuse.
- Other medical conditions or comorbidities, treatment, which in the opinion of the investigator, would interfere with study compliance or data interpretation.
- Presenting any significant biological or clinical anomalies that are not compatible with participation in the study according to the investigator.
- Participant at risk of pregnancy, pregnant or breastfeeding female.
- Participant under guardianship or curatorship.
- Participant under the protection of the Court or deprived of liberty.
- Participant participating in another interventional clinical trial which could interfere with the trial’s results or impact the other trial’s results; or within 5 half-lives of the study investigational treatment, whichever is longer.
- Participant whose current state of health does not allow him/her to give consent.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Portugal | Recruiting | 15 Aug 2025 | 70 |
 Spain | Recruiting | 15 Aug 2025 | 295 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
LOPERAMIDE | Other | PHF00245MIG | ORAL USE | 8 | 12 | SCP1155863 |
Ultra-Levura 250 mg cápsulas duras | Test | CÁPSULAS DURAS | ORAL USE | 500 | 12 | PRD2787365 |
Placebo to Saccharomyces boulardii | Placebo | N/A | — | — | — | N/A |