Efficacy of Prucalopride in Patients with Gastro-Esophageal Reflux Disease and Incomplete Proton Pump Inhibitor Response: A Placebo-Controlled Study

The primary objective of this study is to assess the **efficacy** of prucalopride 2mg as a 4-week add-on treatment in patients with **gastro-esophageal reflux disease** (GERD) who exhibit an incomplete response to proton pump inhibitor (PPI) therapy. This evaluation is clinically relevant as it aims to address the therapeutic gap in GERD management for patients who do not fully respond to standard PPI treatment, potentially offering an alternative therapeutic strategy to improve symptom control and patient outcomes.

Secondary objectives include predicting, based on a 24-hour pH-impedance monitoring and validated questionnaires, which patients are likely to benefit from treatment with prucalopride 2mg. This could enhance personalized treatment approaches by identifying patient subgroups that may experience the most significant therapeutic benefit from prucalopride, thereby optimizing treatment efficacy and resource allocation.

The clinical trial involves participants diagnosed with **gastro-esophageal reflux disease** (GERD) who have shown an incomplete response to proton pump inhibitor (PPI) therapy. The study population includes both male and female subjects aged between 18 to 65 years. Participants are required to have documented evidence of reflux, either through esophagitis or pathological reflux parameters, and a history of typical GERD symptoms during PPI treatment. The trial does not include a vulnerable population. Participants must have been on a daily PPI regimen for at least 12 weeks prior to inclusion, with a minimum of 8 weeks on a twice-daily dosage. Sexually active women of childbearing potential are required to use medically acceptable contraception methods, excluding oral contraceptives due to potential side effects of the study medication. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants are capable of understanding and willing to provide informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **prucalopride** as an add-on treatment for patients with **gastro-esophageal reflux disease** (GERD) who have an incomplete response to proton pump inhibitor (PPI) therapy. This study is a randomized, double-blind, placebo-controlled trial. Participants will be randomly assigned to receive either prucalopride 2 mg or a placebo, both administered orally. The trial is expected to last until December 31, 2026, with recruitment having started on October 1, 2018.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age between 18 and 65 years, documented reflux, and a history of GERD symptoms during PPI treatment. The primary endpoint is the change in acid exposure time, assessed by 24-hour impedance-pH monitoring. Secondary endpoints include changes in the number of reflux episodes, esophageal motility patterns, and symptom severity.

The study involves an initial screening visit, followed by regular follow-up visits to monitor treatment effects and safety. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 8 weeks. Conditions that may lead to early termination from the study include adverse reactions to the treatment or withdrawal of consent. Participants are required to provide informed consent before any protocol-specific procedures are performed.

The clinical trial involves the administration of **Prucalopride Prolepha**, a film-coated tablet containing the active substance **prucalopride**. This medication is chemically synthesized and is provided in a dosage form of 2 mg per tablet. The route of administration is oral, with a maximum daily dose of 2 mg. The treatment period is set for a maximum of 8 weeks. The primary objective of this trial is to evaluate the efficacy of prucalopride as an add-on treatment for patients with gastro-esophageal reflux disease (GERD) who have shown an incomplete response to proton pump inhibitor (PPI) therapy. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.

The study also includes a **placebo** group, where participants will receive a placebo tablet manufactured by Laboratoria Wolfs, Zwijndrecht. 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 appearance of the prucalopride tablets to maintain blinding in the study. The placebo will be administered orally, following the same dosing schedule as the active treatment group, to serve as a comparator in assessing the efficacy of prucalopride.

The efficacy of prucalopride in the treatment of **gastro-esophageal reflux disease** (GERD) with incomplete response to proton pump inhibitor (PPI) therapy will be assessed through a placebo-controlled trial. The primary endpoint for evaluating efficacy is the change in acid exposure time, which will be measured using 24-hour impedance-pH monitoring. Secondary endpoints include changes in the number of reflux episodes, assessed by the same 24-hour impedance-pH monitoring, changes in motility patterns in the esophagus assessed by high-resolution and impedance manometry, and changes in symptom severity, which will be evaluated using a reflux questionnaire known as Request.

The trial involves a 4-week add-on treatment with prucalopride 2 mg. Efficacy parameters will be collected and analyzed at specified timepoints throughout the study duration. The use of validated tools such as impedance-pH monitoring and high-resolution manometry ensures the accuracy and reliability of the data collected. The study aims to provide a comprehensive assessment of prucalopride's efficacy in improving GERD symptoms in patients who have not fully responded to standard PPI therapy.