A Randomized, Double-Blind, Placebo-Controlled Crossover Study of Clebopride Hydrogen Maleate in Patients with Rumination Syndrome

The primary objective of this study is to evaluate the **efficacy** of clebopride 0.5 mg taken three times daily on the perceived overall treatment evaluation in patients with clinically suspected **Rumination Syndrome**. This is assessed using a Likert scoring system, which is clinically relevant as it provides a standardized measure of patient-reported outcomes, crucial for understanding the therapeutic impact of clebopride in managing this condition.

Secondary objectives include assessing the effect of clebopride on several physiological parameters: the number of symptom events reported by the patient during high-resolution impedance manometry, the number of flow events identified on high-resolution impedance manometry, **lower esophageal sphincter** (LES) pressure, the number of transient LES relaxations (TLESRs), and intra-gastric pressure. These secondary measures are important for understanding the mechanistic effects of clebopride on gastrointestinal function and its potential role in alleviating symptoms associated with Rumination Syndrome.

The clinical trial focuses on evaluating the efficacy of clebopride 0.5 mg t.i.d. in individuals diagnosed with **Rumination Syndrome**. The study population includes both male and female participants, with an age range starting from 18 years and above. Participants are required to have a history consistent with probable rumination syndrome, as assessed by a gastroenterologist, and must have completed a gastro-duodenoscopy within the past 12 months showing no anatomical abnormalities of the stomach or esophagus. Additionally, participants should have attempted a treatment regimen equivalent to 20mg of daily omeprazole for two weeks prior to consideration for inclusion. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified. Key inclusion criteria include the requirement for sexually active women of childbearing potential to use medically acceptable contraception and the ability of all subjects to provide informed consent. The selection process for the trial population is not detailed in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, crossover** study to evaluate the efficacy of **clebopride hydrogen maleate** in the treatment of **Rumination Syndrome**. The trial aims to assess the perceived overall treatment evaluation using a Likert scoring system. Participants will be randomly assigned to receive either clebopride 0.5 mg tablets or placebo tablets, both administered orally. The study will involve a crossover design, where participants will switch from one treatment to the other after a specified period, allowing for direct comparison of the effects of clebopride versus placebo.

The trial is expected to last until December 31, 2025, with participant recruitment having commenced on October 1, 2019. The study will include several visits, starting with an inclusion (screening) visit to determine eligibility based on criteria such as age, medical history, and previous diagnostic procedures. Participants must be at least 18 years old, have a history consistent with probable rumination syndrome, and have completed a gastro-duodenoscopy within the past 12 months showing no anatomical abnormalities. Women of childbearing potential must use medically acceptable contraception.

Following the screening, participants will undergo a series of follow-up visits to monitor treatment effects and collect data on primary and secondary endpoints. The primary endpoint is the patients' perceived overall treatment evaluation, while secondary endpoints include overall symptom severity, number of symptom events, and quality of life assessments. The study will conclude with an end-of-study visit to evaluate the final outcomes and ensure participant safety.

Participant involvement is expected to last for the duration of the trial, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial's design ensures that data collected will provide robust evidence on the efficacy of clebopride in treating rumination syndrome, contributing valuable insights to clinical practice.

The clinical trial involves the administration of **MOTILEX** 0.5 mg tablets, which contain the active substance **clebopride hydrogen maleate**. This pharmaceutical form is a tablet, and the medication is administered orally. The dosing regimen for this trial is 0.5 mg taken three times daily (t.i.d.), with a maximum daily dose of 1.5 mg. The total maximum dose over the treatment period is 22.5 mg. The treatment period is set for a maximum of 2 weeks. The tablets are manufactured by ALMIRALL, S.A., and are authorized for use in Italy under the marketing authorization number 026362020. Participant compliance with the dosing schedule will be monitored throughout the trial.

The trial also includes a **placebo** control, which is a tablet manufactured by Laboratoria Wolfs. Each placebo tablet weighs 488 mg and contains the following inactive ingredients: lactose monohydrate (320 mg), carmellose sodium (10 mg), corn starch (70 mg), cellulose microcrystalline (55 mg), silicium dioxide anhydrous (20 mg), and magnesium stearate (13 mg). The placebo is designed to match the experimental medication in appearance and is administered orally with the same frequency as the active treatment, three times daily. The use of a placebo control allows for a double-blind study design, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby reducing bias in the assessment of the treatment's efficacy.

The efficacy of clebopride in the treatment of clinically suspected **Rumination Syndrome** will be assessed through a randomized, double-blind, placebo-controlled, crossover trial. The primary endpoint for evaluating efficacy is the patients' perceived overall treatment evaluation (OTE), which will be measured using a Likert score ranging from -4 to +4. This scoring system will provide a quantitative measure of the patients' perception of treatment effectiveness.

Secondary endpoints include the overall symptom severity (OSS) compared between both treatment periods, which will be assessed at the end of each treatment period. Additional secondary endpoints involve the number of symptom events identified by the patient during High-Resolution Impedance Manometry (HRiM), the number of flow events during HRiM, esophagogastric junction (EGJ) pressure during HRiM, the number of transient lower esophageal sphincter relaxations (TLESRs), and the number of events with increased intra-gastric pressure. Furthermore, daily symptom diaries using the Leuven Postprandial Distress Scale (LPDS) with an additional question concerning retrograde bolus flow, symptom severity at week 2 using the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and quality of life at week 2 using the Patient Assessment of Gastrointestinal Disorders Quality of Life (PAGI-QOL) will be utilized to gather comprehensive data on treatment efficacy.