Multicenter randomized controlled clinical trial comparing ebastine and mebeverine as treatment of irritable bowel syndrome

The primary objective of this multicenter randomized controlled clinical trial is to perform a randomized superiority trial comparing the clinical efficacy of **ebastine** and **mebeverine** in the treatment of **Irritable Bowel Syndrome** (IBS). This objective is clinically relevant as it aims to determine which of the two treatments provides superior relief of IBS symptoms, potentially guiding therapeutic decisions and improving patient outcomes. Additionally, the trial seeks to evaluate the impact of treatment with ebastine compared to mebeverine on quality of life and quality-adjusted life years, which are critical measures of the overall benefit of a treatment in terms of both clinical effectiveness and patient well-being.

The clinical trial focuses on individuals diagnosed with **Irritable Bowel Syndrome** (IBS), specifically targeting those who meet the Rome IV criteria for non-constipated IBS. The study population includes both male and female participants, aged between 18 and 65 years. Participants are required to have no organic cause for their symptoms, with specific exclusions for conditions such as coeliac disease, lactose intolerance, inflammatory bowel disease, and giardiasis. However, individuals with lactose intolerance may be included if they show no improvement on a lactose-free diet over a six-week period. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' lifestyle factors, such as diet and physical activity, are not specified in the available data.

The clinical trial is designed as a **randomized**, **controlled**, and double-blind study to evaluate the efficacy of **ebastine** and **mebeverine hydrochloride** in the treatment of **irritable bowel syndrome** (IBS). The trial aims to assess the superiority of ebastine over mebeverine in terms of clinical efficacy, as well as the impact on quality of life and quality-adjusted life years. The study will involve a total of 200 participants who meet the inclusion criteria, which include fulfilling the Rome IV criteria for non-constipated IBS, being aged between 18 and 65, and having no organic cause for their symptoms. The trial is expected to run from April 2023 to October 2026, with a maximum treatment period of 12 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility. This will be followed by regular follow-up visits throughout the 12-week treatment period to monitor the primary endpoints, which include abdominal pain intensity and global relief of symptoms. Secondary endpoints will also be assessed, such as weekly response rates and changes in IBS symptom severity scores. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted to evaluate the overall response to the treatment.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. The trial will utilize a placebo-controlled design, with participants randomly assigned to receive either the active treatment or a placebo. The study will ensure that both the participants and the investigators are blinded to the treatment allocation to maintain the integrity of the trial results.

The clinical trial involves the administration of **Ebastine**, marketed as EBASTINE TEVA 20 mg FILMTABLETTEN. This experimental medication is provided in the form of a **film-coated tablet**. The active substance, **ebastine**, is of chemical origin. The medication is administered orally with a maximum daily dose of 40 mg, and the treatment period extends up to 12 weeks. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

The comparator treatment in this trial is **Mebeverine Hydrochloride**, marketed as Duspatalin Retard 200 mg capsules met verlengde afgifte, hard. This medication is provided as a **prolonged-release capsule, hard**. The active substance, **mebeverine hydrochloride**, is also of chemical origin. The administration route is oral, with a maximum daily dose of 400 mg, and the treatment duration is similarly set at 12 weeks. Compliance monitoring is conducted to ensure participants adhere to the prescribed dosing regimen.

In addition to the active treatments, the study includes placebo controls, referred to as Duspatalin-dummy and Ebastine-dummy. These placebos are utilized to maintain the study's blinding and are administered in a manner consistent with the active treatments, although specific pharmaceutical forms and active substances are not applicable. The use of placebos is critical for evaluating the true efficacy of the experimental and comparator treatments.

The efficacy of the clinical trial comparing **ebastine** and **mebeverine** for the treatment of irritable bowel syndrome (IBS) will be assessed using both primary and secondary endpoints. The primary endpoints include the evaluation of **Abdominal Pain Intensity** and **Global Relief of Symptoms**. Secondary endpoints will further explore the treatment's impact through various measures, such as the **Overall Response** combining Abdominal Pain Intensity and Global Relief of Symptoms, assessed as a weekly responder for at least 6 weeks during the 12-week treatment period. Additional secondary endpoints include weekly response assessments up to Week 12, during the run-out period, and specific responses related to abdominal pain intensity and global symptom relief.

Other secondary endpoints involve the assessment of **Stool Consistency**, with weekly responder criteria for both overall and clinical responses, and the weekly number of days with at least one stool of consistency 6 or 7. The **IBS-SSS score**, ranging from 0 to 500, will be evaluated at baseline and at 12 weeks, with a response defined as a decrease of at least 50 points. Quality of life will also be assessed at Week 12. These efficacy parameters will be measured and collected at specified timepoints throughout the trial, ensuring a comprehensive evaluation of the treatment's impact on IBS symptoms and patient quality of life.