Efficacy and Safety Evaluation of Myrrh, Coffee Charcoal, and Chamomile Extract in Diarrhea-Predominant and Mixed-Type Irritable Bowel Syndrome

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) and mixed-type irritable bowel syndrome (IBS-M). This is clinically relevant as IBS-D and IBS-M are common subtypes of irritable bowel syndrome, which significantly impact patients' quality of life. The trial aims to provide evidence on the therapeutic potential of MYRRHINIL-INTEST® in managing these conditions, potentially offering a new treatment option for affected individuals.

The clinical trial focuses on evaluating the efficacy, safety, and tolerability of MYRRHINIL-INTEST® in treating **diarrhoea predominant irritable bowel syndrome** (IBS-D) and irritable bowel syndrome of the mixed type (IBS-M). The study population comprises both male and female participants aged between 18 and 75 years, with a confirmed diagnosis of IBS-D or IBS-M according to the Rome IV criteria. Participants are required to maintain their current lifestyle and dietary habits throughout the study duration. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Key inclusion criteria involve the absence of significant weight loss, nocturnal symptoms, or a family history of colon carcinoma. Participants must have a negative pregnancy test if applicable and agree to keep a patient diary diligently. Exclusion criteria include chronic inflammatory bowel diseases and clinically relevant elevated calprotectin levels. The trial population was selected based on these criteria to ensure a representative sample of the target demographic.

The clinical trial is designed to evaluate the **efficacy** and safety of MYRRHINIL-INTEST® compared to a placebo in patients with diarrhoea-dominant irritable bowel syndrome (IBS-D) and mixed-type irritable bowel syndrome (IBS-M). This is a randomized, double-blind, controlled trial. The trial is expected to last until December 31, 2024, with recruitment having started on May 6, 2020. Participants will be involved in the study for a maximum treatment period of 8 weeks, during which they will receive either the active treatment or placebo in the form of coated tablets administered orally.

The study includes several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the **screening** visit, eligibility criteria are assessed, including confirmation of IBS-D or IBS-M diagnosis according to Rome IV criteria, and exclusion of other conditions such as chronic inflammatory bowel diseases. Participants must also agree to maintain their lifestyle and dietary habits throughout the study. Follow-up visits occur at regular intervals to monitor the primary and secondary endpoints, which include assessments of abdominal pain, stool consistency, and overall gut health. The end-of-study visit will evaluate the overall efficacy and safety of the treatment.

Participants are expected to diligently maintain a patient diary to record daily symptoms, including pain intensity, stool frequency, and consistency. The primary endpoint is assessed by a responder criterion specific to IBS-D and IBS-M subgroups, requiring a response in abdominal pain and additional assessments of stool consistency or overall bowel health. Secondary endpoints include various symptom assessments and quality of life evaluations. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial aims to provide comprehensive data on the treatment's impact on IBS-D and IBS-M, contributing to the understanding of its therapeutic potential.

The clinical trial involves the administration of **MYRRHINIL-INTEST®**, a coated tablet formulation containing active substances including **myrrh**, **coffee charcoal**, and **dry extract from chamomile flower** (4-6:1), with ethanol 60% (m/m) as the extraction solvent. The product is manufactured by REPHA GMBH BIOLOGISCHE ARZNEIMITTEL and is classified under the ATC code A07, which pertains to antidiarrheals and intestinal anti-inflammatory/anti-infective agents. The maximum daily dose is 12 tablets, with a total maximum dose of 672 tablets over an 8-week treatment period. The route of administration is oral, and the study-specific labeling is applied to the product.

The trial also includes a **placebo** control, which is produced by the same manufacturer and is identical in appearance to the test product but does not contain any active pharmaceutical ingredients. The placebo is used to assess the efficacy and safety of MYRRHINIL-INTEST® in comparison. The placebo is administered orally in the same dosage form and frequency as the experimental medication to ensure blinding and maintain the integrity of the study design.

The efficacy of MYRRHINIL-INTEST® in the treatment of **diarrhoea-dominant irritable bowel syndrome (IBS-D)** and mixed-type irritable bowel syndrome (IBS-M) will be assessed using both primary and secondary endpoints. The primary endpoint involves a responder criterion, which varies between IBS-D and IBS-M patients. For both subgroups, a response in abdominal pain, measured by the Numerical Rating Scale (NRS pain), is required. Additionally, for IBS-D patients, stool consistency will be evaluated using the Bristol Stool Form Scale, while IBS-M patients will also undergo an overall assessment of bowel health changes using the Patient Global Impression of Improvement (PGI-I) scale.

Secondary endpoints include several parameters: abdominal pain intensity, recorded daily by patients using an 11-point NRS and assessed during visits 1-5; the number of spontaneous bowel movements and stool consistency, documented daily in a patient diary and evaluated at the study center during visits 1-5; and the frequency of incomplete bowel evacuation, mucus, and/or blood in the stool, also recorded daily. The severity of IBS symptoms will be assessed using the IBS-Severity Scoring System (IBS-SSS) during visits 1-5, and quality of life will be measured with the IBS-QoL questionnaire. An overall assessment of gut health changes will be conducted using the PGI-I scale at visit 4. Both the investigator and the patient will provide a global assessment of efficacy during visits 3 and 4 using a 4-point scale. Additional secondary endpoints include the reduced use of emergency medications, compliance with study medication, adverse events, vital signs, and clinical chemistry and hematology assessments at specified visits. Tolerability will be evaluated by both the investigator and the patient during visits 3 and 4.