Efficacy and Safety Evaluation of Myrrh, Coffee Charcoal, and Chamomile Extract in Diarrhea-Predominant Irritable Bowel Syndrome: A Controlled Trial

The primary objective of this controlled clinical trial is to evaluate the **efficacy**, safety, and tolerability of MYRRHINIL-INTEST® compared to placebo in the treatment of patients with diarrhoea-dominant irritable bowel syndrome (**IBS-D**). This objective is clinically relevant as IBS-D is a common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits, significantly impacting patients' quality of life. The trial aims to provide evidence on the therapeutic potential of MYRRHINIL-INTEST®, which contains active substances such as myrrh, coffee charcoal, and dry extract from chamomile flower, in managing symptoms associated with IBS-D.

The clinical trial focuses on evaluating the efficacy, safety, and tolerability of MYRRHINIL-INTEST® compared to a placebo in treating **diarrhoea-dominant irritable bowel syndrome** (IBS-D). The study population comprises both male and female participants aged between 18 and 75 years, with a confirmed diagnosis of IBS-D. Participants are required to have undergone a colonoscopy if they are over 55 years of age within the past five years. The trial does not include a vulnerable population. Participants are expected to maintain their current lifestyle and dietary habits throughout the study duration. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **efficacy** and safety of MYRRHINIL-INTEST® compared to a placebo in patients diagnosed with diarrhoea-predominant irritable bowel syndrome (IBS-D). This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to conclude by December 31, 2024, with recruitment having commenced on July 7, 2020. The total duration of the trial for each participant is approximately 8 weeks, during which they will be required to attend multiple study visits.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, a negative pregnancy test for those of childbearing potential, and a confirmed IBS-D diagnosis. Participants must also have undergone a colonoscopy if over 55 years of age within the last five years. Following the screening, participants will attend a series of follow-up visits, specifically visits 1 through 6, where various assessments will be conducted. These include the evaluation of stool frequency and consistency, abdominal pain, and the presence of any adverse events. The primary endpoint is the responder rate, defined by a decrease in abdominal pain and stool consistency. Secondary endpoints include changes in stool frequency, the number of spontaneous defecations, and the assessment of IBS-D symptoms severity.

Participants are expected to maintain a consistent lifestyle and dietary habits throughout the study and are required to keep a detailed patient diary. The end-of-study visit will involve a comprehensive assessment of the participant's condition and the collection of final data. Conditions that may lead to early termination from the study include non-compliance with the study protocol, the occurrence of significant adverse events, or withdrawal of consent by the participant. The trial aims to provide robust data on the treatment's impact on IBS-D, contributing valuable insights into its management.

The clinical trial involves the administration of **MYRRHINIL-INTEST®**, a coated tablet formulation, as the experimental medication. Each tablet contains 100 mg of **myrrh**, 50 mg of **coffee charcoal**, and 70 mg of **dry extract from chamomile flower** (4-6:1), with ethanol 60% (m/m) as the extraction solvent. The medication is intended for **oral use**. Participants are instructed to take the medication up to a maximum daily dose of 12 tablets, with a total maximum dose of 684 tablets over the course of the study. The treatment period is set for a maximum of 8 weeks. The trial aims to evaluate the efficacy, safety, and tolerability of MYRRHINIL-INTEST® in patients with diarrhoea-dominant irritable bowel syndrome (IBS-D).

The study also includes a **placebo** group, which receives a placebo product manufactured to match the test product in appearance but lacking any active pharmaceutical ingredients. The placebo is provided by the same manufacturer to ensure consistency in the trial's blinding process. The placebo is administered in the same manner as the experimental medication, with the same dosing schedule and treatment period, to maintain the integrity of the study's design.

Efficacy in the clinical trial investigating MYRRHINIL-INTEST® versus placebo for the treatment of **diarrhoea-dominant irritable bowel syndrome (IBS-D)** will be assessed using a co-primary endpoint. This endpoint is defined by responder criteria, which include a responder rate characterized by a decrease in abdominal pain by at least 30% and a reduction in days with at least one stool of consistency 6 or 7 by at least 50%. Secondary endpoints will further evaluate efficacy through various parameters, including changes in stool frequency, number of spontaneous defecations, and stool consistency, all recorded daily in the patient's diary. The severity of IBS-D symptoms will be assessed using the IBS-Severity Scoring System (IBS-SSS) during visits 1 to 6, and quality of life will be determined using the IBS-QoL questionnaire. Global assessment of efficacy will be conducted by both the investigator and the patient during visits 3 to 6 using a 4-point scale.

Data collection will occur at multiple timepoints throughout the study, specifically during visits 1 to 6. The Bristol Stool Form Scale will be utilized to measure stool consistency, and patient diaries will be used to document daily occurrences of spontaneous defecations, feelings of incomplete defecation, and the presence of mucus and/or blood in the stool. Compliance with study medication will be monitored through documentation in the patient diary and drug accountability checks at visits 4 and 6. Adverse events, vital parameters, and clinical chemistry and haematology will be assessed throughout the study, with specific evaluations at visits 1, 4, and 6. The assessment of tolerability will be conducted by both the investigator and the patient during visits 3 to 6.