Efficacy and Safety Evaluation of Naronapride Dihydrochloride Trihydrate in Moderate Idiopathic or Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of a 12-week treatment with naronapride compared to placebo on disease signs and symptoms in participants with at least moderate idiopathic or diabetic gastroparesis. This is clinically relevant as it aims to determine the therapeutic potential of naronapride in improving gastric motility and alleviating symptoms associated with gastroparesis, a condition characterized by delayed gastric emptying that can significantly impact quality of life.

Secondary objectives include: - Determining the optimal dose-level of naronapride after completion of a 12-week treatment in participants with at least moderate idiopathic or diabetic gastroparesis. - Evaluating the safety and tolerability of naronapride compared to placebo in the same participant group. These objectives are crucial for establishing the appropriate dosing regimen and ensuring the safety profile of naronapride, thereby facilitating its potential use in clinical practice.

The clinical trial involves **118 participants** diagnosed with **idiopathic or diabetic gastroparesis**. The study population comprises both men and women aged between 18 and 75 years. Participants were selected based on a history of gastroparesis symptoms persisting for at least three months, confirmed evidence of delayed gastric emptying, and an average weekly total symptom score of 2.0 or higher. The trial excludes individuals with mechanical or anatomical obstructions, stenosis, structural diseases, or gastric ulcers, as verified by upper gastrointestinal endoscopy or imaging techniques. Participants have a **Body Mass Index** ranging from 16 to less than 35 kg/m². The trial does not include any vulnerable populations, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and tolerability of a 12-week treatment with **Naronapride** in adult participants with at least moderate **idiopathic or diabetic gastroparesis**. The trial aims to determine the optimal dose of Naronapride by comparing it to a placebo. The study will involve multiple visits over the course of the trial, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, history of gastroparesis symptoms, and evidence of delayed gastric emptying. Participants must have an average weekly total symptom score of at least 2.0 and a Body Mass Index between 16 and 35 kg/m². Exclusion criteria include any mechanical or anatomical obstructions, stenosis, structural diseases, or gastric ulcers.

The trial will consist of several key visits: the baseline visit (Visit 2), where initial measurements and assessments are conducted; follow-up visits to monitor progress and any adverse effects; and the end-of-study visit (Visit 6), where the primary endpoint, the change in average weekly total symptom score from baseline to the end of treatment, will be evaluated. Secondary endpoints include changes in specific symptom scores such as nausea, early satiety, postprandial fullness, upper abdominal pain, number of vomiting episodes, and bloating.

Participants are expected to be involved in the study for the entire 12-week treatment period unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent. The trial is anticipated to conclude by March 2025, with recruitment having started in July 2022. The study will utilize film-coated tablets of Naronapride and placebo, administered orally, with varying doses to identify the most effective treatment regimen. The trial is not classified as low intervention and is categorized as a phase IIb study, focusing on dose-finding and efficacy evaluation.

The clinical trial involves the administration of **Naronapride dihydrochloride trihydrate**, a chemical compound, in the form of film-coated tablets. The investigational products, identified as NAT01, NAT02, and NAT03, are manufactured by DR. FALK PHARMA G.M.B.H. Each formulation is designed for oral administration. NAT01 is administered at a maximum daily dose of 30 mg, with a total maximum dose of 2520 mg over a 12-week period. NAT02 is administered at a maximum daily dose of 60 mg, with a total maximum dose of 5040 mg over the same period. NAT03 is administered at a maximum daily dose of 120 mg, with a total maximum dose of 10080 mg. The treatment period for each formulation is 12 weeks, and the dosing schedule is designed to evaluate the efficacy, safety, and tolerability of Naronapride in participants with at least moderate idiopathic or diabetic gastroparesis.

The trial also includes a **placebo** group, which receives placebo film-coated tablets. The placebo is used as a comparator to assess the efficacy of the investigational drug, Naronapride. The placebo tablets are administered orally, following the same dosing schedule as the active treatment groups, to maintain the double-blind nature of the study. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol and to accurately assess the outcomes of the treatment.

The efficacy of the clinical trial will be assessed by evaluating the impact of a 12-week treatment with **naronapride** compared to placebo on disease signs and symptoms in participants with at least moderate idiopathic or diabetic gastroparesis. The primary endpoint for efficacy evaluation is the change in the average weekly total symptom score from baseline (visit 2) to the end of treatment or withdrawal (visit 6). Secondary endpoints include changes in the modified and composite average weekly total symptom score, as well as changes in the average weekly symptom scores for nausea, early satiety, postprandial fullness, upper abdominal pain, number of vomiting episodes, and bloating from baseline to the end of treatment or withdrawal.

These efficacy parameters will be measured and collected at specified visits throughout the trial duration. The trial is designed as a double-blind, randomized, placebo-controlled, dose-finding phase IIb study. The assessment of efficacy will involve the use of validated scales to quantify symptom changes, ensuring a robust and reliable evaluation of the treatment's impact on the participants' condition. The trial aims to provide comprehensive data on the efficacy of naronapride in managing symptoms associated with gastroparesis.