Methods for treating diabetic gastroparesis

Abstract

This disclosure provides a method for treating diabetic gastroparesis.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 491,823, filed on 23 March 2023, the contents of which are incorporated herein by reference.

[0002] Technical field This disclosure provides a method for treating diabetic gastroparesis. [Background technology]

[0003] background Gastroparesis is defined as impaired gastric emptying in the absence of physical obstruction of the gastric outflow tract. Symptoms include early satiety, postprandial bloating, nausea, vomiting, and abdominal pain. This condition is often associated with diabetes or may occur after gastric surgery. It can also be idiopathic. Gastroparesis affects the nutritional status of patients, particularly those with diabetes, and severe symptoms of gastroparesis can lead to malnutrition, esophagitis, and other complications such as Mallory-Weiss lacerations. Gastroparesis negatively impacts the patient's quality of life, leading to reduced social interaction, poor work function, and the development of anxiety or depression.

[0004] The primary treatment for gastroparesis involves nutritional management and supplementation, including fluid and electrolyte replacement. Pharmacological therapy aims to increase gastric emptying and accelerate intestinal transit time. Currently, metoclopramide, a dopamine D2 receptor antagonist, is the only drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of gastroparesis. While effective, this drug easily crosses the blood-brain barrier and causes central nervous system (CNS) side effects in up to 40% of patients. Common CNS effects associated with metoclopramide treatment include restlessness, drowsiness, fatigue, and malaise. However, the main safety concern associated with metoclopramide treatment is the development of tardive dyskinesia. Tardive dyskinesia is a disorder characterized by involuntary movements of the face, tongue, or limbs, and is often irreversible. The increased risk of developing tardive dyskinesia correlates with the duration of treatment. Therefore, it is recommended that treatment with metoclopramide not exceed 12 weeks.

[0005] New methods are needed to treat diabetic gastroparesis. [Overview of the project]

[0006] In some embodiments, the present disclosure provides a method for treating a person diagnosed with diabetic gastroparesis, comprising administering a dosage form containing 10 mg or 15 mg of deudomperidone by BID, wherein the administration reduces the severity of the person's gastroparesis-related symptoms compared to baseline. [Brief explanation of the drawing]

[0007] [Figure 1] This is the trial scheme for Example 3. PK subset analysis: After approximately 30 subjects in PK subset A have completed their fifth visit, new PK and safety data will be evaluated. Interim analysis: If approximately 50% of the randomized subjects have completed their end-of-treatment (EOT) visit or have been discontinued early during the trial, one open-label IA will be conducted. [Modes for carrying out the invention]

[0008] Detailed description of exemplary embodiments In this disclosure, the singular forms “a,” “an,” and “the” include references to the plural forms, and references to specific numbers include at least that specific value unless otherwise explicitly indicated by the context. Thus, for example, a reference to “material” is a reference to at least one such material and their equivalents known to those skilled in the art.

[0009] When a value is represented as an approximation by the use of the descriptor "approximately," it is understood that a particular value forms another embodiment. Generally, the use of the term "approximately" refers to an approximate value that may vary depending on the desired characteristic that the disclosed subject aims to achieve and should be interpreted on its function within the particular context in which it is used. Those skilled in the art may interpret this as a matter of course. In some cases, the number of significant figures used for a particular value may be one non-restrictive way of determining the degree of the word "approximately." In other cases, the gradual change used for a set of values ​​may determine the expected value available for the term "approximately" for each value. If any, all ranges are inclusive and combinable; that is, a reference to a value stated in a range includes all values ​​within that range.

[0010] Where a list is presented, please understand that, unless otherwise stated, each individual element of that list and any combination of that list should be interpreted as a separate embodiment. For example, a list of embodiments presented as "A, B, or C" should be interpreted as including embodiments "A", "B", "C", "A or B", "A or C", "B or C", or "A, B, or C".

[0011] The terms "subject" and "patient" are used interchangeably and typically refer to a mammal. In some embodiments, the patient or subject is a human. In other embodiments, the patient or subject is a veterinary or farm animal, a breeding animal or a pet, or an animal used in the conduct of clinical research.

[0012] "Treating" or variations thereof refers to removing or reducing at least one physical parameter of a disease or disorder.

[0013] As used interchangeably herein, the "Dudgeon peridone" and "d4-peridone" have the following structure: TIFF2026511098000002.tif33128, and refers to 1-{3-[4-(5-chloro-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidin-1-yl]propyl}-2,3-dihydro(4,5,6,7-D4)-1H-1,3-benzodiazol-2-one.

[0014] References to Dudgeon peridone, where described, may also include pharmaceutically acceptable salts, esters, hydrates, solvates, prodrug forms, and derivatives thereof, which are broadly defined as modified or partially substituted Dudgeon peridone compounds, examples of which include, but are not limited to, the addition of a single atom, the addition of a reactive group, the addition of a functional group, the formation of a dimer or multimer, a conjugate to another compound such as an antibody, etc.

[0015] "Pharmaceutically acceptable" refers to properties and / or substances that are acceptable to the patient from a pharmacological / toxicological perspective and to the pharmaceutical chemist from a physical / chemical perspective regarding composition, formulation, stability, patient acceptability, and bioavailability.

[0016] Pharmaceutically acceptable salts include salts with pharmaceutically acceptable acids or bases, such as inorganic acids (e.g., hydrochloric acid, sulfuric acid, phosphoric acid, diphosphate, hydrobromic acid, hydroiodic acid, and nitric acid), and organic acids (e.g., citric acid, fumaric acid, maleic acid, malic acid, mandelic acid, ascorbic acid, oxalic acid, succinic acid, tartaric acid, benzoic acid, acetic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, cyclohexylsulfamic acid (cyclamic acid), or p-toluenesulfonic acid). Pharmaceutically acceptable bases include alkali metals (e.g., sodium or potassium), alkaline earth metals (e.g., calcium or magnesium), hydroxides, and organic bases (e.g., alkylamines, arylalkylamines, and heterocyclic amines).

[0017] The abbreviation "D" used herein refers to deuterium (deuterium or 2 This refers to the stable isotope of hydrogen, H). Such an example of "D" is an amount of deutherium exceeding the natural distribution of deutherium. In some embodiments, D has a deutherium enrichment of about 1% or more. In other embodiments, D has a deutherium enrichment of about 5% or more. In yet another embodiment, D has a deutherium enrichment of about 10% or more. In yet another embodiment, D has a deutherium enrichment of about 20% or more. In yet another embodiment, D has a deutherium enrichment of about 30% or more. In yet another embodiment, D has a deutherium enrichment of about 40% or more. In yet another embodiment, D has a deutherium enrichment of about 50%. In yet another embodiment, D has a deutherium enrichment of about 60% or more. In other embodiments, D has a deutherium enrichment of about 70% or more. In yet another embodiment, D has a deutherium enrichment of about 80% or more. In yet another embodiment, D has a deutherium enrichment of about 90% or more. In further embodiments, D has a deuterium enrichment of about 98% or more of deuterium. In further embodiments, D has a deuterium enrichment of about 99% or more of deuterium. In further embodiments, D has a deuterium enrichment of at least 99% of deuterium.

[0018] As used herein, "baseline" refers to a human score or average of scores on a particular scale prior to any administration of duodenperidone described herein. The baseline can be established, for example, immediately prior to duodenperidone administration, or up to about 7 days before duodenperidone administration, or up to about 14 days before. For example, the baseline can be established about 30 minutes before the first administration of duodenperidone. In other embodiments, the baseline can be established 1 day before the first administration of duodenperidone. In other embodiments, the baseline can be established 2 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 3 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 4 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 5 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 6 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 7 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 8 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 9 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 10 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 11 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 12 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 13 days before the first administration of duodenperidone. In other embodiments, the baseline can be established 14 days before the first administration of duodenperidone.

[0019] This disclosure provides a method for treating a person diagnosed with diabetic gastroparesis. As used herein, the term “diabetic gastroparesis” refers to a person having diabetes and gastroparesis. In some embodiments, the person has type 1 diabetes. In other embodiments, the person has type 2 diabetes. As used herein, the term “gastroparesis” refers to a disorder involving delayed gastric emptying in the absence of physical obstruction of the gastric outflow tract.

[0020] This method involves administering a dosage form containing 10 mg or 15 mg of dudonperidone to a human via BID (Bio-Injection) administration. In some embodiments, 20 mg of dudonperidone is administered to the human. In other embodiments, 30 mg of dudonperidone is administered to the human. For example, the free base of dudonperidone is administered to the human.

[0021] Dudomperidone may be administered as needed to achieve the desired daily dose. For example, dudomperidone may be administered in divided doses. In some embodiments, dudomperidone is administered twice daily (BID). In further embodiments, a 20 mg dose of dudomperidone is administered in 10 mg BIDs. In other embodiments, a 30 mg dose of dudomperidone is administered in 15 mg BIDs. In yet another embodiment, a 20 mg dose of dudomperidone is administered in 20 mg BIDs, or as a single 10 mg capsule. In yet another embodiment, a 30 mg dose of dudomperidone is administered in 15 mg BIDs, as a single 10 mg capsule and as a single 5 mg capsule.

[0022] Dudomperidone can be formulated in dosage form, such as solid form, for administration. In some embodiments, the pharmaceutical formulation is formulated in the form of tablets, caplets, capsules, powders, or softgels, or a combination thereof. In other embodiments, the pharmaceutical formulation is formulated in the form of tablets. In further embodiments, the pharmaceutical formulation is formulated in the form of caplets. In yet another embodiment, the pharmaceutical formulation is formulated in the form of capsules. In yet another embodiment, the pharmaceutical formulation is formulated in the form of powders. In yet another embodiment, the pharmaceutical formulation is formulated in the form of softgels. In yet another embodiment, the dosage form is a single capsule containing 10 mg of dudomperidone. In yet another embodiment, the dosage form is a single capsule containing 5 mg of dudomperidone and a single capsule containing 10 mg of dudomperidone.

[0023] The dosage form, for example, a capsule, contains one or more of (i) a medium-chain triglyceride, (ii) glyceryl distearate, (iii) butylated hydroxyanisole, and (iv) butylated hydroxytoluene. In some embodiments, the dosage form contains glyceryl distearate. As used herein, the term "glyceryl distearate" refers to a compound having the following components: glyceryl and two stearic acids, which combine to form a chemically stable molecule. In certain embodiments, glyceryl distearate is glyceryl 1,3-glyceryl distearate. In further embodiments, the capsule contains 9.75 mg of glyceryl distearate.

[0024] In other embodiments, the dosage form, for example, a capsule, contains a medium-chain triglyceride. As used herein, the term “medium-chain triglyceride” refers to a triglyceride in which the fatty acid portion has an aliphatic tail of about 6 to about 12 carbon atoms. In some embodiments, the fatty acid portion has an aliphatic tail of 6, 7, 8, 9, 10, 11, or 12 carbon atoms. In further embodiments, the fatty acid aliphatic tails are identical. In other embodiments, the fatty acid aliphatic tails are different. In yet another embodiment, the fatty acid has an aliphatic tail of 6 carbon atoms, i.e., the medium-chain triglyceride is caproic acid. In yet another embodiment, the fatty acid has an aliphatic tail of about 8 carbon atoms, i.e., the medium-chain triglyceride is caprylic acid. In yet another embodiment, the fatty acid has an aliphatic tail of about 10 carbon atoms, i.e., the medium-chain triglyceride is capric acid. In a further embodiment, the fatty acid has an aliphatic tail of about 12 carbon atoms, i.e., the medium-chain triglyceride is lauric acid. In yet another embodiment, the capsule contains 85.1 mg of medium-chain triglyceride. In yet another embodiment, the capsule contains 80.1 mg of medium-chain triglyceride.

[0025] In further embodiments, the dosage form, for example, a capsule, contains one or more antioxidants. In some embodiments, the dosage form contains butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), or a combination thereof. In other embodiments, the antioxidant is BHA. In further embodiments, the antioxidant is BHT. In further embodiments, the antioxidants are BHA and BHT. In further embodiments, the capsule contains 0.05 mg of butylated hydroxytoluene. In other embodiments, the capsule contains 0.10 mg of butylated hydroxyanisole. In further embodiments, the capsule contains 0.1 mg of butylated hydroxyanisole and 0.05 mg of butylated hydroxytoluene.

[0026] In certain embodiments, the capsule contains one or more of (i) 85.1 mg of medium-chain triglycerides, (ii) 9.75 mg of glyceryl distearate, (iii) 0.1 mg of butylated hydroxyanisole, and (iv) 0.05 mg of butylated hydroxytoluene. In certain embodiments, the capsule contains (i) 85.1 mg of medium-chain triglycerides, (ii) 9.75 mg of glyceryl distearate, (iii) 0.1 mg of butylated hydroxyanisole, and (iv) 0.05 mg of butylated hydroxytoluene. In further embodiments, the capsule contains one or more of (i) 80.1 mg of medium-chain triglycerides, (ii) 9.75 mg of glyceryl distearate, (iii) 0.1 mg of butylated hydroxyanisole, and (iv) 0.05 mg of butylated hydroxytoluene. In yet another embodiment, the capsule contains (i) 80.1 mg of medium-chain triglycerides, (ii) 9.75 mg of glyceryl distearate, (iii) 0.1 mg of butylated hydroxyanisole, and (iv) 0.05 mg of butylated hydroxytoluene.

[0027] The patient has an average weekly ANMS GCSI-DD nausea subscale score of 2 or higher prior to administration of dudomperidone. In some embodiments, the patient has an average weekly ANMS GCSI-DD nausea subscale score of 2, 3, or 4. In other embodiments, the patient has an ANMS GCSI-DD nausea subscale score of 2 or higher for at least about 14 days prior to administration of dudomperidone.

[0028] The patient has at least one vomiting episode per week on average prior to administration of dudomperidone. As used herein, the term “vomiting” refers to the oral expulsion of gastrointestinal contents by contraction of the muscles of the intestines and the chest and abdominal wall. In some embodiments, the patient has at least one vomiting episode of any severity on average per week. In other embodiments, the patient has at least one, two, three, four, or five vomiting episodes per week on average prior to administration of dudomperidone.

[0029] Those skilled in the art will be able to calculate / determine the ANMS GCSI-DD score. For example, see "The Use Manual for the ANMS GCSI-DD," American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary, 2018 (https: / / www.fda.gov / media / 125038 / download). The ANMS GCSI-DD manual scoring method is generated by summing the scores of the symptom items (e.g., number of episodes of nausea, early satiety, postprandial bloating, epigastric pain, and vomiting) and then dividing by 5, which is the number of items in the gastroparesis-related symptom score. Therefore, the maximum total symptom score may be (5 symptoms × maximum score 4 ÷ 5). Thus, the maximum score is 20 / 5 = 4. A higher score in the ANMS GCSI-DD reflects a more severe symptom. For example, see the "User Manual for the ANMS GCSI-DD," incorporated herein by reference, from the Federal Drug Administration (https: / / www.fda.gov / media / 125038 / download).

[0030] Preferably, the administration reduces the severity of gastroparesis-related symptoms in humans compared to baseline. Gastroparalysis-related symptoms include one or more of the following: postprandial nausea, postprandial vomiting, postprandial bloating, early satiety, abdominal distension, epigastric pain, or abdominal pain. In some embodiments, the gastroparesis-related symptom is postprandial nausea. In other embodiments, the gastroparesis-related symptom is postprandial vomiting. In further embodiments, the gastroparesis-related symptom is postprandial bloating. In yet another embodiment, the gastroparesis-related symptom is early satiety. In yet another embodiment, the gastroparesis-related symptom is abdominal distension. In other embodiments, the gastroparesis-related symptom is epigastric pain. In yet another embodiment, the gastroparesis-related symptom is abdominal pain.

[0031] The reduction in severity is based on a composite score of the mean human ANMS GCSI-DD nausea subscale score and vomiting subscale score. Those skilled in the art will be able to calculate such subscales using the techniques described herein. In some embodiments, the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 0.5 points compared to baseline. In other embodiments, the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 0.5, 1, 1.5, 2, 2.5, 3, 3.5, or 4 points compared to baseline. In a further embodiment, the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 0.5–4, 0.5–3.5, 0.5–3, 0.5–2.5, 0.5–2, 0.5–1.5, 0.5–1, 1–4, 1–3.5, 1–3, 1–2.5, 1–2, 1–1.5, 1.5–4, 1.5–3.5, 1.5–3, 1.5–2.5, 1.5–2, 2–4, 2–3.5, 2–3, 2–2.5, 2.5–4, 2.5–3.5, 2.5–3, 3–4, 3–3.5, or 3.5 or 4 points compared to baseline.

[0032] In other embodiments, the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 30% compared to baseline. In further embodiments, the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to baseline. In yet another embodiment, the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by 30-100%, 30-90%, 30-80%, 30-70%, 30-60%, 30-50%, 30-40%, 40-100%, 40-90%, 40-80%, 40-70%, 40-60%, 40-50%, 50-100%, 50-90%, 50-80%, 50-70%, 50-60%, 60-100%, 60-90%, 60-80%, 60-70%, 70-100%, 70-90%, 70-80%, 80-100%, 80-90%, or 90-100% compared to baseline.

[0033] In some embodiments, after administration of dudonperidone, the percentage of days free of gastroparesis-related symptoms in humans increases compared to baseline. In other embodiments, the PAGI-QoL score in humans improves compared to baseline. In yet another embodiment, the GERDQ score in humans improves compared to baseline. In yet another embodiment, the PGIS score in humans improves compared to baseline.

[0034] manner Embodiment 1: A method for treating a person diagnosed with diabetic gastroparesis, comprising administering 10 mg or 15 mg of dudomperidone as a BID, wherein the administration reduces the severity of gastroparesis-related symptoms in the person.

[0035] Embodiment 2: The method of Embodiment 1, wherein the reduction in severity is based on a composite score of the mean human ANMS GCSI-DD nausea subscale score and vomiting score.

[0036] Embodiment 3: A method substantially described herein.

[0037] TIFF2026511098000004.tif231170 [Examples]

[0038] Example 1 A. Explanation of the exam (i) Overview of the test design This study is a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of dudonperidone after 12 weeks of treatment in adults with diabetic gastroparesis.

[0039] The safety of dudomperidone will be evaluated from the time of informed consent to the end of the follow-up period. Participants will be tracked for efficacy and adherence to the study drug throughout the double-blind treatment period. Plasma concentrations of dudomperidone will also be measured at elective visits during the double-blind treatment period.

[0040] The total duration of the trial is approximately 18 weeks, including a screening and induction period of less than 5 weeks, a 12-week double-blind treatment period, and a follow-up period of up to 1 week. During participation, participants will complete 8 in-person visits (participants who recorded delayed gastric emptying within 2 years of their first visit may complete their second visit by telephone).

[0041] Participants who have completed the screening and introductory periods and are still eligible will be randomized in parallel to one of three treatment groups in a 1:1:1 ratio over a 12-week period: ● Dudomperidone 15 mg is administered as a single 10 mg capsule and a single 5 mg capsule in a BID (Bio-Injection) regimen; ● Dudomperidone 10 mg is administered as a single 10 mg capsule of dudomperidone and a single placebo capsule in a BID (Bio-Injection) regimen; or ● Dudomperidone placebo was administered as two matching placebo capsules in a BID (Bio-Injection Derived) regimen.

[0042] Approximately 400 subjects (133 subjects per treatment group) will be randomized, and 363 subjects are expected to complete a 12-week double-blind treatment period. Subjects will be stratified by their baseline composite score of mean ANMS GCSI-DD nausea subscale score and vomiting subscale score according to their sex at birth (female, male) (≤2.6 vs. >2.6).

[0043] Pharmacokinetics All participants in the study will have trough PK samples collected within 60 minutes prior to administration of the study drug during their 5th and 7th visits.

[0044] Participants may choose to participate in a PK subset, in which post-administration PK samples will also be collected at their fifth visit. These participants will remain at the clinic for up to approximately 3 hours after receiving their morning study drug. In addition to blood samples taken for PK within 60 minutes prior to study drug administration, blood samples will be taken from participants in the PK subset approximately 1 hour and 2 hours after administration. If a participant wishes to remain at the clinic longer and is able to do so, a PK sample will also be taken approximately 3 hours after administration. If a participant wishes to return to the clinic, additional samples may be taken within the post-administration window (4-8 hours and / or 8-12 hours) on the same day. Participants will be instructed to record the date and time of each administration two days prior to their fifth visit and not to take the study drug at home on the day of their fifth visit. Post-administration PK samples will be collected within ±15 minutes of the nominal time.

[0045] After approximately 30 participants in the PK subset have completed their fifth visit, the iDMC will blind individual participant assignments and evaluate new PK and safety data to determine the dosage level to carry over for the remainder of the trial.

[0046] After the initial data review is complete, post-administration samples will be collected from the subset of subjects at the 5th, 6th, and / or 7th visits, within at least 1–4 hours, 4–8 hours, or 8–12 hours post-administration windows. For subjects who choose to provide more than one sample, efforts will be made to collect each sample within different windows. Subjects will be instructed to record the date and time of each administration two days prior to their visit and not to take the study drug at home on the day of their visit.

[0047] In the event of a SAE or AE that leads to the cancellation of the procedure, efforts will be made to collect a PK sample as quickly as possible.

[0048] interim analysis During the trial, if approximately 70% of randomized subjects complete their end-of-treatment (EOT) visits or discontinue early, an interim analysis (IA) will be conducted. iDMCs will be collected to evaluate safety, early futility, and potential sample size recalculations. The IA for the primary endpoint will only evaluate early futility or increased sample size. The trial will not be discontinued due to overwhelming efficacy.

[0049] Overall test design and procedure To be eligible to participate in the study, participants must meet all selection criteria and not meet any exclusion criteria. Participants will be evaluated as follows: ● Screening period (first visit, -35 days to -22 days): ○ The screening procedure will be implemented, and subjects will begin washing out any applicable excluded medications. Subjects are required to wash out all prohibited medications for at least 14 days or 5 half-lives (whichever is longer) before the start of the ANMS GCSI-DD baseline period (defined as the 7 or 14 days prior to randomization, depending on whether the subject meets randomization criteria 4a or 4b) and / or before performing GEBT at the second visit. ○ Starting in the evening of the screening visit, participants should record their ANMS GCSI-DD, PAGI-QoL, GERDQ, PGIS, and the use of acceptable emergency medications according to Tables 1A and 1B. ● Implementation period (second visit, -21 days to -1 day): ○ For subjects who recorded delayed gastric emptying within two years of their first visit, this visit can be concluded by telephone to assess their adherence to their journal, concomitant treatments, and adverse events (AEs). If a subject requires additional assessments that necessitate a visit to the clinic, the subject may report to the clinic any additional procedures corresponding to the scheduled outpatient visit. ○ Participants are required to complete the ANMS GCSI-DD questionnaire daily and to record the use of acceptable emergency medications daily. ○ The mean of daily ANMS GCSI-DD measurements obtained over a 7-day or 14-day period prior to randomization constitutes the "baseline" measurement. ○ GEBT: For subjects who did not record delayed gastric emptying within two years of their first visit, a GEBT will be performed on one day between day -21 and day -12 (including both ends). The GEBT will be performed after a washout of at least 14 days or 5 half-lives (whichever is longer) from the medications listed below. Subjects will fast for at least 8 hours before the GEBT. The GEBT will be performed using a standardized method. 13 Breath samples were collected twice before the intake of the C-fortified meal, and then at 45, 90, 120, 150, 180, and 240 minutes after meal intake. Fasting blood glucose was assessed before the GEBT to confirm a blood glucose level of ≤275 mg / dL. If a subject's fasting blood glucose level was >275 mg / dL, the GEBT was not performed. Subjects were permitted to return to the clinic within 1-3 days to complete the study, or they may be excluded from the study if they no longer met the criteria for stable, well-controlled blood glucose. On the day of the GEBT, subjects should visit the clinic after an overnight fast and take their regular medications (including any diabetes treatments), except for prohibited concomitant medications. Subjects requiring insulin will self-administer their usual morning insulin injection, taking their fasting status into consideration. Subjects will be instructed to bring insulin to the clinic as needed. Fasting blood glucose was assessed before the gastric emptying assessment to confirm a blood glucose level of ≤275 mg / dL. Additional insulin was administered (titrated based on meal calorie intake), and blood glucose levels were confirmed to be ≤275 mg / dL before the gastric emptying procedure. Similarly, indicated hypoglycemia (hypoglycemia, blood glucose <60 mg / dL) was managed. ○ The subjects must wash out the following drugs within 14 days prior to the start of the baseline period or within 5 half-lives (whichever is longer) in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary up to the end of the trial. ■ Metoclopramide, ■ Dom Peridone, ■ Erythromycin, ■ Pyridostigmine, ■ Chronic opioid use (individuals permitted to use opioids once during the treatment period, within 72 hours, as needed), ■ Daily use of marijuana and / or tetrahydrocannabinol (Participants who test positive for tetrahydrocannabinol at their first visit may be eligible to continue the study if they have a prescription for the drug, have been taking a stable dose for at least six months prior to screening, and agree to avoid daily use of tetrahydrocannabinol during their participation in the study. Participants who have not recorded delayed gastric emptying within two years prior to their first visit and are required to complete a gastric emptying breath test must agree to refrain from prescribed marijuana and / or tetrahydrocannabinol for two weeks prior to this test), ■ Anticholinergic drugs, and ■ Antiemetics (excluding emergency antiemetics specified in the protocol). ● 12-week double-blind treatment period (3rd visit to 7th visit, days 1 to 84): ○ Adherence to ANMS GCSI-DD will be assessed at the time of randomization (day 1), and a rate of 75% or higher, or approval from the trial sponsor, is required to be eligible for the trial. ○ The investigational drug (dudonperidone and / or placebo capsules) will be administered for 84 (±4) days, and a safety evaluation will be conducted. The ANMS GCSI-DD questionnaire will be completed at approximately the same time each evening. ○ Complete the PAGI-QoL and GERDQ at the clinic during the first, third, fourth, fifth, sixth, and seventh visits prior to the first administration of the investigational drug. ○ All subjects participating in the study will have trough PK samples taken at their 5th and 7th visits, within 60 minutes prior to administration of the study drug. Subjects may choose to participate in a PK subset, in which post-administration PK samples will also be taken at their 5th visit. These subjects will remain at the clinic for up to approximately 3 hours after morning administration of the study drug. In addition to the blood sample taken for PK within 60 minutes prior to administration of the study drug, subjects in the PK subset will have blood samples taken approximately 1 hour and 2 hours after administration. If a subject wishes to and is able to remain at the clinic longer, a PK sample will also be taken approximately 3 hours after administration. If a subject wishes to return to the clinic, additional samples may be taken within the post-administration window (4-8 hours and / or 8-12 hours) on the same day. Subjects will be instructed to record the date and time of each administration two days prior to their 5th visit and not to take the study drug at home on the day of their 5th visit. Post-administration PK samples will be taken within ±15 minutes of the nominal time. Safety is assessed through evaluation of adverse events (AEs), vital signs, physical examination, clinical laboratory evaluation (chemistry, hematology, coagulation, urinalysis, and prolactin), and 12-lead ECG findings. Furthermore, a single, optional PGx blood sample can be collected at any point during the treatment period. ● Follow-up period: (8th visit, 91st day [±3 days]): ○ Participants will be asked to make follow-up visits approximately one week (±3 days) after the last dose of the study drug to evaluate adverse events (AEs), changes in concomitant therapy (including the use of emergency medications), vital signs, 12-lead ECG, prolactin, chemistry, hematology, and coagulation.

[0050] (Table 1A) Procedure Schedule TIFF2026511098000005.tif213170TIFF2026511098000006.tif224170

[0051] (Table 1B) Procedure Schedule TIFF2026511098000007.tif137170TIFF2026511098000008.tif199170

[0052] Unscheduled visits and / or additional follow-up may be required. For example, patients with clinically significant abnormal laboratory findings, unresolved TEAEs, SAEs requiring follow-up examinations and reviews, or clinically significant AEs may require further evaluation.

[0053] B. Selection and cancellation of targets Screening procedures, including vital sign assessment, may be repeated one or two times for eligibility purposes. Subjects who have been screened but did not meet the inclusion / exclusion criteria (despite potentially undergoing repeated screening assessments, if applicable) may be considered for rescreening.

[0054] (i) Selection criteria Based on the screening evaluation, individuals who meet all of the following criteria are eligible to participate in the examination. 1. Be a male or female aged 18 or older. 2. You have been diagnosed with type 1 or type 2 diabetes according to the criteria of the American Diabetes Association. 3. Currently, the patient is diagnosed with diabetic gastroparesis as defined below. a. Gastrointestinal symptoms perceived to be consistent with gastroparesis within 6 months prior to screening (e.g., postprandial nausea / vomiting, postprandial bloating, early satiety, abdominal distension, and / or epigastric / abdominal pain), and b. Symptoms of delayed gastric emptying recorded within the past two years, as determined by GEBT, scintigraphy, radioactive motility capsule, or manometry. Subjects exhibiting the symptoms described in selection criterion 3a but who have not recorded delayed gastric emptying within the past two years prior to their first visit should undergo the induction period (between day -21 and day -12, including both ends). 13 GEBT can be completed using C-spirulina platensis. To be eligible to participate, GEBT t 1 / 2 It must be 110 minutes or longer. GEBT t 1 / 2 For subjects with a time limit of <110 minutes, an examination may be considered. 4. 18-45 kg / m² at screening 2 They have a BMI (including both ends). 5. The patient has an HbA1c level of 10% or less at the time of screening and has stable, well-controlled blood glucose levels. 6. Men with a female partner of potential pregnancy must agree to use two medically acceptable, highly effective methods of contraception from day 1 to day 90 after the last dose of the study drug. Medically acceptable, highly effective methods of contraception for men with a female partner of potential pregnancy include latex condoms containing spermicide, diaphragms containing vaginal spermicide, cervical caps containing spermicide, indwelling intrauterine devices (hormonal or non-hormonal), contraceptive implants, and oral contraceptives. 7. Male participants must agree to refrain from donating sperm for 90 days starting from day 1 after the final dose of the study drug. 8. Women with a male partner must be surgically infertile (hysterectomy and / or bilateral oophorectomy), at least one year postmenopausal (follicle-stimulating hormone levels within the postmenopausal range confirmed at the screening visit), or agree to use a medically acceptable and highly effective method of contraception from 14 to 30 days after the last dose of the study drug. Medically acceptable and highly effective methods of contraception for women with a male partner include latex condoms containing spermicide, diaphragms containing intravaginal spermicide, cervical caps containing spermicide, indwelling intrauterine devices (hormonal or non-hormonal), contraceptive implants, and oral contraceptives. 9. Willingness to refrain from long-acting GLP-1 agonists, SGLT-2 inhibitors, or pramulintide from screening to the end of treatment. Subjects currently taking GLP-1 agonists or SGLT-2 inhibitors may be considered for the study if they are willing to discontinue their medication for three days prior to the start of the ANMS GCSI-DD baseline period and agree to remain discontinuing medication throughout the study treatment period. 10. You understand and can follow all trial visits, procedures, restrictions, and discontinuation of medication (including medication to treat gastroparesis).

[0055] (ii) Exclusion criteria Individuals who meet any of the following criteria will be excluded from participating in the examination. 1. A known cause of gastroparesis other than diabetes (e.g., idiopathic gastroparesis and / or gastroparesis resulting from surgery, viral disease, cancer, scleroderma, or other neurological disorders). 1. The patient has been hospitalized within the past year prior to their first visit for diabetic gastroparesis and / or diabetic ketoacidosis. 2. The patient has a history or current history of clinically significant arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsades de pointes. 3. Having evidence (based on screening or baseline assessment) or a history of clinically significant immunological, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies). Surgical conditions. Cancer (excluding basal cell carcinoma or squamous cell carcinoma of the skin, and cancers that have resolved before the screening visit or have been in remission for more than 5 years). Any condition that may significantly interfere with the absorption, distribution, metabolism, or excretion of the study drug. Cholecystectomy and appendectomy are permitted if the procedure was performed more than 6 months prior to screening. 4. The patient has a history of a prolactin-releasing pituitary tumor (i.e., prolactinoma). 5. Having known or suspected hypogonadism, current clinically significant menstrual abnormalities (e.g., oligomenorrhea or amenorrhea), gynecomastia, galactorrhea, or other clinical features that may be consistent with hyperprolactinemia. 6. The participant has received a pyloric injection of botulinum toxin within six months of screening and / or is scheduled to receive an injection during the course of the study. 7. The patient has a history of pyloroplasty, pyloric myotomy, or gastrointestinal endoscopic myotomy. 8. At the time of screening, the patient has total bilirubin, alkaline phosphatase, AST, or ALT levels greater than 2×ULN, or has a Child-Pugh classification grade of B or C. 9. Serum creatinine levels exceeding 1.5 × ULN, or <30 mL / min / 1.73 m² using the Chronic Kidney Disease Epidemiology Collaboration formula at the time of screening. 2 It has an estimated glomerular filtration rate. 10. The patient has significantly abnormal thyroid-stimulating hormone levels at the time of screening. 11. Unable to perform a GEBT or having a fasting blood glucose level of ≥275 mg / dL on the day of the GEBT. This criterion applies only to subjects who have no record of delayed gastric emptying within two years prior to screening and who require completion of a GEBT to confirm eligibility. If a subject's fasting blood glucose level is ≥275 mg / dL, a GEBT will not be performed. The subject may be permitted to return to the clinic within 1-3 days to complete the study, or may be excluded from the study if the subject no longer meets the criteria for stable, well-controlled blood glucose. 12. The individual has a known allergy to eggs or spirulina. This criterion applies only to individuals who have no record of delayed gastric emptying within two years prior to screening and who require completion of a GEBT to confirm eligibility. 13. Use investigational drugs, prescription drugs, or over-the-counter drugs as follows: a. Actively participating in an experimental therapy trial. Received experimental therapy with a small molecule within 30 days of randomization or within 5 half-lives (whichever is longer), or received experimental therapy with a large molecule within 90 days of randomization or within 5 half-lives (whichever is longer). b. Regarding CYP3A4 inhibitors and inducers (drugs, herbal supplements, dietary supplements, nutraceuticals, or foods): ■ For subjects who choose to provide PK samples exceeding the trough sample at the 5th and 7th visits, all CYP3A4 inhibitors and / or inducers within 14 days of the initial dose of the study drug or within 5 half-lives (whichever is longer) will be excluded until the end of the study. ■ For all other subjects, all CYP3A4 inhibitors and / or inducers within 14 days of the first dose of the study drug or within 5 half-lives (whichever is longer) up to the end of the study will be excluded. Weak and moderate CYP3A4 inhibitors and inducers are acceptable. ■ For all participants, the use of grapefruit, grapefruit products, starfruit products, and Seville oranges is prohibited from 48 hours before randomization until the end of treatment. c. Use of motility stimulants (including, but not limited to, metoclopramide, domperidone, erythromycin, pyridostigmine, etc.), other drugs and medications that may affect gastric emptying (e.g., all chronic opioids [subjects are permitted to use opioids once during the treatment period, for a maximum of 72 hours, if necessary], daily use of marijuana and / or tetrahydrocannabinol [requires prescription by a healthcare professional, and the dose must be stable for more than 6 months for non-daily use], and all anticholinergics), and antiemetics (except protocol-specified emergency antiemetics) within 14 days or 5 half-lives prior to the start of the ANMS GCSI-DD baseline period up to the end of the study (whichever is longer). d. Use of antipsychotics, antidepressants, anxiolytics, or prescription hypnotics (excluding stable doses taken more than 6 months prior to screening). 14. A positive drug or alcohol test result at screening without medical explanation, or a history of alcohol dependence or substance abuse as defined in the Diagnostic and Statistical Manual of Mental Disorders (4th edition) within two years prior to screening, and / or typically consuming 14 or more alcoholic beverages per week. One alcoholic beverage is equivalent to 1 / 2 pint beer (285 mL), one glass of spirits (25 mL), or one glass of wine (125 mL). If a false positive is suspected, a confirmatory drug or alcohol test may be performed using a different method. Subjects showing a positive test result for tetrahydrocannabinol at their first visit may be eligible to continue the study, provided they have a prescription for the drug, have been taking a stable dose for at least six months prior to screening, and agree to avoid daily use of tetrahydrocannabinol during their participation in the study. Patients who have not recorded delayed gastric emptying within two years prior to their first visit and who are required to complete the GEBT must agree to refrain from prescribed marijuana and / or tetrahydrocannabinol for two weeks prior to this test. 15. There is evidence that you are continuing to use illegal drugs. 16. The patient has a known history of an eating disorder or an ongoing eating disorder within two years of the screening visit. 17. At the time of screening, the patient is positive for human immunodeficiency virus antibody, RNA-based hepatitis C virus antibody, or hepatitis B surface antigen. 18. Are you currently receiving treatment with weight-loss medication, or have you had weight-loss surgery in the past (e.g., gastric bypass surgery)? 19. You are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the course of the examination. 20. Unable to swallow medication. 21. Currently receiving parenteral nutrition, or having a nasogastric or other enteral tube (e.g., PEG or PEJ tube) for nutritional support or decompression. 22. Having known or suspected gastric outflow tract obstruction (e.g., peptic stenosis) or other mechanical obstruction of the gastrointestinal tract, as recorded by upper gastrointestinal endoscopy or upper gastrointestinal radiography series within the past two years. 23. Having a known history or current diagnosis of intestinal malabsorption or pancreatic exocrine disease. 24. Patients with a history of gastric surgery, such as fundoplication, gastrectomy, vagus nerve transection, pyloroplasty, or obesity treatment. Patients with a gastric pacemaker in appropriate location may have the pacemaker turned off at least 14 days before the start of the ANMS GCSI-DD baseline period and throughout the remainder of the study. A history of diagnostic endoscopy is not exclusionary. 25. Having any medical condition or mental disorder that could interfere with the conduct of the study or expose the subject to an unacceptable risk. 26. I have been previously exposed to dudonperidone. 27. Lack of response to domperidone, or a history of known hypersensitivity or intolerance to domperidone or any excipient in dudomperidone formulations. 28. It is deemed inappropriate for any other reason that may increase the risk to the subject during participation or interfere with the interpretation of the study results.

[0056] (iii) Randomization criteria Participants who meet the following criteria will be randomized at their third visit (Day 1). 1. All selection / exclusion criteria remain met. 2. Within 14 days or within 5 half-lives (whichever is longer) before the start of the ANMS GCSI-DD baseline period until the end of the trial, no use of motility agents (including, but not limited to, metoclopramide, domperidone, erythromycin, pyridostigmine, etc.), other drugs and medications that can affect gastric emptying (e.g., all chronic opioid agents [subjects are permitted to use opioids once within 72 hours during the treatment period if necessary], daily use of marijuana and / or tetrahydrocannabinol [prescription by a medical professional is required and the dosage needs to be stable for more than 6 months for non-daily use], and all anticholinergic drugs), and antiemetics (except for the emergency antiemetics specified in the protocol), and there is an intention not to use such agents until the end of the trial. 3. Demonstrate a definitive diagnosis of diabetic gastroparesis as defined below. a. Gastrointestinal symptoms (e.g., postprandial nausea / vomiting, postprandial fullness, early satiety, abdominal distension, and / or upper abdominal / abdominal pain) that were felt to be consistent with gastroparesis within 6 months before screening, and b. Gastric emptying delay symptoms recorded within the past 2 years, determined by GEBT, scintigraphy, wireless motility capsule, or manometry. Subjects who exhibit the symptoms described in Selection Criterion 3a but have no recorded gastric emptying delay within the past 2 years at the first visit can complete the GEBT using C - Spirulina platensis during the introduction period (between - 21 days and - 12 days, inclusive). 13 C - Spirulina platensis can be used to complete the GEBT. To obtain eligibility, the GEBT t 1 / 2 should be 110 minutes or more. Subjects with a GEBT t 1 / 2 <110 minutes may be considered for the trial. 4. Meet either one of the following criteria "a" or "b". a. Have an ANMS GCSI-DD score that meets the following during the 14 days before randomization when the subject is not taking motility agents or antiemetics (except for the emergency medications specified in the protocol). ■ An average weekly nausea subscale score of 2 or more ( "moderate" or more); ■ There are no days with a nausea subscale score of 0; and ■ At least two vomiting incidents per week. b. The subject kept a diary for at least 7 days, met the following ANMS GCSI-DD score criteria, and took the maximum dose of an approved emergency medication (i.e., 25 mg of promethazine, 4 mg of ondansetron, or a single dose of an over-the-counter ginger product per day for 3 days per week). ■ A nausea subscale score of 3 or higher ("severe") for at least 4 days out of 7; ■ There are no days with a nausea subscale score of 0; and ■ At least two vomiting incidents per week. Vomiting (emesis) is clinically defined as the oral expulsion of gastrointestinal contents due to the contraction of the muscles of the intestines and the chest and abdominal wall, while reflux is defined as the involuntary expulsion of stomach contents into the mouth. Participants should be taught the difference between vomiting and reflux, which are defined as the act of bringing swallowed food back into the mouth, and should record vomiting episodes accordingly. 5. Adherence to ANMS GCSI-DD during the baseline period, defined as 75% or higher, or approval by the trial sponsor.

[0057] C. Test Objectives (i) Main purpose The primary objective of this study was to evaluate the ability of dudomperidone to significantly reduce the severity of gastroparesis-related symptoms compared to baseline in adult patients with diabetic gastroparesis, compared to placebo, based on a composite score of the mean ANMS GCSI-DD nausea subscale and vomiting subscale scores over the last two weeks of a 12-week treatment period.

[0058] (ii) Secondary purposes A secondary objective of this study is to evaluate the effects of dudomperidone compared to placebo on the following parameters in adult patients with diabetic gastroparesis: ● Relationship between ANMS GCSI-DD nausea subscale scores and vomiting subscale scores and PGIS and PGIC over a 12-week treatment period. ● Percentage of subjects who showed clinical improvement in symptoms of gastroparesis, based on the average composite score of the ANMS GCSI-DD nausea subscale score and vomiting subscale score over the last two weeks of the 12-week treatment period, had a history of lack of response, or were unable to tolerate metoclopramide therapy or other motility enhancers such as erythromycin, neostigmine, or bethanechol. ● Percentage of patients who achieved a reduction of 30% or more from baseline in their ANMS GCSI-DD total score and subscale scores during the last two weeks of the 12-week treatment period. ● Percentage of respondents showing a mean reduction of 0.5 or more from baseline in the ANMS GCSI-DD nausea subscale score and vomiting subscale score over the last two weeks of the 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on mean ANMS GCSI-DD total score and subscale scores over the last two weeks of a 12-week treatment period. ● Percentage of symptom-free days in the ANMS GCSI-DD total score and subscale scores over the last two weeks of the 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms in adult subjects with diabetic gastroparesis compared to baseline, based on the mean composite score of ANMS GCSI-DD nausea subscale and vomiting subscale scores over the last 6 weeks of a 12-week treatment period. ● Percentage of patients who achieved a 30% or greater reduction in their ANMS GCSI-DD total score and subscale scores from baseline during the last 6 weeks of the 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on mean ANMS GCSI-DD total score and subscale scores over the last 6 weeks of a 12-week treatment period. ● Percentage of symptom-free days in the ANMS GCSI-DD total score and subscale scores over the last 6 weeks of the 12-week treatment period. ● Changes from the PGIS baseline. ● Changes from PGIC baseline.

[0059] (iii) exploratory purpose; The exploratory objectives of this study include evaluating the following in adults with diabetic gastroparesis: ● Changes from baseline in the PAGI-QoL device survey. ● Changes from the GERDQ baseline. ● Changes in HbA1c, insulin requirements, and diabetes medication use from baseline to week 12. ● Characterization of the absorption of dudomperidone under stable conditions and the concentration of its primary metabolites. ● Characterization of the exposure-response relationship of dudonperidone, as well as various measurements of efficacy and / or safety, may also be performed.

[0060] (iv) Safety goals The safety objective includes evaluating the safety of dudonperidone compared to placebo in adults with diabetic gastroparesis.

[0061] D. Experimental Therapy (i) Treatment group This trial is designed to include three treatment groups, each containing 133 participants. Participants who have completed the screening and induction periods and are still eligible will be randomized in parallel to one of the three treatment groups in a 1:1:1 ratio over 12 weeks. ● Dudomperidone 15 mg is administered as a single 10 mg capsule and a single 5 mg capsule in a BID (Bio-Injection) regimen; ● Dudomperidone 10 mg is administered as a single 10 mg capsule of dudomperidone and a single placebo capsule in a BID (Bio-Injection) regimen; or ● Dudomperidone placebo was administered as two matching placebo capsules in a BID (Bio-Injection Derived) regimen.

[0062] (ii) Randomization and blinding This is a randomized, double-blind trial. Randomization of subjects will be managed by an IRT system. Subjects who have completed the screening and induction periods and are still eligible will be randomized in parallel to one of three treatment groups in a 1:1:1 ratio over 12 weeks. Randomization will be performed at the third visit (day 1). Subjects will be stratified according to sex at birth (female, male) and by baseline composite scores of mean ANMS GCSI-DD nausea subscale and vomiting subscale scores (≤2.6 vs. >2.6).

[0063] Blinding is maintained by administering two dosing units per dose. Therefore, subjects randomized to a 10 mg dose level will take one 10 mg capsule and one placebo capsule per dose. Subjects randomized to a 15 mg dose level will take one 10 mg capsule and one 5 mg capsule per dose. Finally, subjects randomized to placebo will take two matching placebo capsules per dose.

[0064] Blinding of the investigational drug is maintained through database locking. Randomized subjects who discontinue the trial early will not be replaced.

[0065] (iii) Drug supply Dudonperidone capsules consist of dudonperidone active ingredient in oval, blue, opaque softgel capsules of size 2C. Each dudonperidone softgel capsule contains either 10 mg or 5 mg of active dudonperidone active ingredient. The dudonperidone-filled formulation contains the inactive components listed in Table 2.

[0066] (Table 2) Inactive components of dudonperidone TIFF2026511098000009.tif24170

[0067] Corresponding placebo softgel capsules containing the same inactive ingredient (excluding dudonperidone active pharmaceutical ingredient) are also provided. See Table 3.

[0068] (Table 3) Inactive components of placebo TIFF2026511098000010.tif24170

[0069] Softgel capsules (capsules containing the active ingredient dudomperidone and placebo capsules) are packaged in blister packs to obtain the required dose for the study.

[0070] (iv) Administration of the investigational drug All randomized subjects will receive one dose of the blinded study drug (dudonperidone and / or placebo capsule) orally as a BID (Body Intake) with approximately 240 mL of water. For designated individuals, an interval of approximately 12 hours (e.g., 8:00 AM to 8:00 PM) will be maintained between each dose. Subjects will be required to fast for 2 hours prior to and 1 hour after all doses. Subjects in the PK subset who will provide post-administration PK samples at their fifth visit will be required to fast for at least 8 hours prior to their morning dose of the study drug. Subjects will be provided with a dose of the study drug for self-administration that will not be administered at the clinic.

[0071] If a subject forgets to take their scheduled medication and realizes they have forgotten within two hours of the scheduled time, they should be instructed to take the assigned dose of the study drug as soon as they realize they have forgotten. If a subject realizes they have not taken their medication more than two hours after the scheduled time, they should be instructed to skip this dose of the study drug and resume taking the assigned dose of the study drug at the next scheduled time.

[0072] Pretreatment and concomitant treatment and / or procedures (v) Drugs, foods, and / or procedures that are excluded During the trial, the use of the following investigational drugs, prescription drugs, or over-the-counter drugs is not permitted. ● Use of antipsychotics, antidepressants, anxiolytics, or prescription hypnotics (excluding stable doses taken more than 6 months prior to screening). ● Plum lynchid. ● SGLT-2 inhibitors or GLP-1 agonists with long half-lives (e.g., Bizleon® [exenatide sustained-release], Victoza® [liraglutide], Tanazem® [albiglutide], or Trulicity® [dulaglutide]). ● Experimental therapy with small molecules received within 30 days of randomization or within 5 half-lives (whichever is longer), or experimental therapy with large molecules received within 90 days of randomization or within 5 half-lives (whichever is longer). ● Regarding CYP3A4 inhibitors and inducers (drugs, herbal supplements, dietary supplements, nutraceuticals, or foods): ○ For subjects who choose to provide PK samples exceeding the trough sample at the 5th and 7th visits, all CYP3A4 inhibitors and / or inducers within 14 days of the initial administration of the study drug or within 5 half-lives (whichever is longer) up to the end of the study will be excluded. ○ For all other subjects, all CYP3A4 inhibitors and / or inducers within 14 days of the first dose of the study drug or within 5 half-lives (whichever is longer) up to the end of the study will be excluded. Weak and moderate CYP3A4 inhibitors and inducers are acceptable. ○ For all participants, the use of grapefruit, grapefruit products, star fruit products, and Seville oranges is prohibited from 48 hours before randomization until the end of treatment. ● Any drug, herbal supplement, dietary supplement, or nutraceutical with potential for QT prolongation within 28 days prior to the first dose of the study drug before the end of the study. ● Use of motility enhancers (including, but not limited to, metoclopramide, domperidone, erythromycin, pyridostigmine, etc.), other drugs and medications that may affect gastric emptying (e.g., all chronic opioids [subjects are permitted to use opioids once during the treatment period, within 72 hours if necessary], daily use of marijuana and / or tetrahydrocannabinol [requires prescription by a healthcare professional, and the dose must be stable for more than 6 months for non-daily use]), and all anticholinergics), and antiemetics (except protocol-specified emergency antiemetics) within 14 days or 5 half-lives prior to the start of the ANMS GCSI-DD baseline period up to the end of the study (whichever is longer). Participants who test positive for tetrahydrocannabinol at their first visit may be eligible to continue the study, provided they have a prescription for the drug, have been taking a stable dose for at least six months prior to screening, and agree to avoid daily use of tetrahydrocannabinol during their participation in the study. Participants who have not recorded delayed gastric emptying within two years prior to their first visit and are required to complete a GEBT must agree to refrain from prescribed marijuana and / or tetrahydrocannabinol for two weeks prior to this test. ● Pyloric injection of botulinum toxin within 6 months of screening and during the testing process. ● Treatment with weight-loss medication, or past weight-loss surgery (e.g., gastric bypass surgery). ● Parenteral nutritional support, or the presence of a nasogastric or other enteral tube (e.g., PEG or PEJ tube) for nutritional support or decompression.

[0073] Those requiring further treatment with prohibited substances may discontinue the study treatment and undergo follow-up study procedures.

[0074] (vi) Restricted drugs and / or procedures Patients experiencing severe symptoms of gastroparesis may take promethazine (Phenergan®) 25 mg or ondansetron (Zofran®) 4 mg.

[0075] (vii) Permitted drugs and / or procedures Weak and moderate inhibitors and inducers of CYP3A4 are permitted in subjects not participating in PK subsets.

[0076] If a subject has been taking a stable dose of antipsychotics, antidepressants, anxiolytics, or prescription sleep medications more than six months prior to screening, they are permitted to continue taking these medications.

[0077] Patients are permitted to use opioids once during the treatment period, within a maximum of 72 hours, if necessary.

[0078] Other drugs that have not been explicitly or previously excluded may be permitted after approval (e.g., emergency medicines).

[0079] (viii) First aid Patients experiencing severe symptoms of gastroparesis may take promethazine (Phenergan) 25 mg or ondansetron (Zofran) 4 mg orally, as follows:

[0080] Patients should be encouraged to use over-the-counter ginger (e.g., as capsules, soft chews, chewing gum, oil, or tea) up to 1000 mg once daily before using promethazine or ondansetron. Before taking any over-the-counter product, patients should confirm that the particular product does not contain any protocol-prohibited ingredients.

[0081] During the washout period (from day 35 to day 22), patients may take emergency medication as needed.

[0082] However, during the 3-week induction period (-21 to -1 day), patients experiencing severe symptoms of gastroparesis may take only a single dose of promethazine 25 mg, ondansetron 4 mg, or an over-the-counter ginger product, three days a week. During the ANMS GCSI-DD baseline period, patients should be strongly encouraged to avoid emergency medications whenever possible, and if they are used, they should be used sparingly.

[0083] If a patient's symptoms of gastroparesis are severe enough to require more than the maximum tolerable dose of emergency medication, and they complete a 7-day diary and meet the randomization criteria, including randomization criterion 4b, the patient may proceed directly to randomization.

[0084] After randomization, emergency medication use is limited to one dose per day for a maximum of three days per week, only if the participant experiences nausea and / or vomiting of CTCAE grade 2 or higher. If a participant uses emergency medication once daily for three days per week for two consecutive weeks, the participant will be discontinued from the study due to lack of efficacy. Participants requiring further treatment with prohibited drugs may discontinue the study treatment and undergo follow-up procedures.

[0085] E. Evaluation of effectiveness (i) Primary efficacy endpoint The primary efficacy endpoint of this study is to evaluate the effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline in adult patients with diabetic gastroparesis, compared to placebo, based on a composite score of the mean ANMS GCSI-DD nausea subscale score and vomiting subscale score over the last two weeks of the 12-week treatment period.

[0086] (ii) Secondary efficacy endpoints The secondary efficacy endpoints of this study include the following evaluation of the effect of dudomperidone compared to placebo in adults with diabetic gastroparesis: ● Estimation based on a composite score of mean ANMS GCSI-DD nausea subscale and vomiting subscale scores, using PGIS and PGIC as anchors over a 12-week treatment period. ● Percentage of subjects with a history of lack of response or inability to tolerate metoclopramide therapy or other exercise stimulants such as erythromycin, neostigmine, or bethanechol, showing a greater than 30% reduction from baseline based on the mean composite score of the ANMS GCSI-DD nausea subscale score and vomiting subscale score over the last two weeks of the 12-week treatment period. ● Percentage of patients identified as responders, defined as a mean decrease of 0.5 or more from baseline in the ANMS GCSI-DD nausea subscale score and vomiting subscale score over the last two weeks of the 12-week treatment period. ● Percentage of patients who achieved a 30% or greater reduction from baseline in the mean composite score of the ANMS GCSI-DD nausea subscale score and vomiting subscale score over the last two weeks of the 12-week treatment period. ● Percentage of patients who achieved a mean reduction of 30% or more from baseline in the ANMS GCSI-DD vomiting subscale over the last two weeks of the 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD nausea subscale score over the last two weeks of a 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD vomiting subscale score over the last two weeks of a 12-week treatment period. ● Percentage of patients who achieved a mean reduction of 30% or more from baseline in their ANMS GCSI-DD nausea subscale score over the last two weeks of the 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD total score over the last two weeks of a 12-week treatment period. ● Percentage of patients who achieved a mean ANMS GCSI-DD total score reduction of 30% or more from baseline over the last two weeks of the 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD early satiety subscale score over the last two weeks of a 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD postprandial bloating subscale score over the last two weeks of a 12-week treatment period. ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD upper abdominal pain subscale score over the last two weeks of a 12-week treatment period. ● Percentage of symptom-free days for each dose of dudomperidone during the last two weeks of a 12-week treatment period, in the ANMS GCSI-DD total score, composite score of nausea and vomiting scores, nausea score, vomiting score, early satiety score, postprandial bloating score, and upper abdominal pain score (symptom days are defined as >mild [ANMS GCSI-DD score > 2]). ● All of the above endpoints, which were evaluated during the last two weeks of the 12-week treatment period, will also be evaluated during the last six weeks of the 12-week treatment period. ● Changes in PGIS from baseline to week 12 with each dose of dudomperidone. ● Changes in PGIC from baseline to week 12 with each dose of dudomperidone.

[0087] (iii) Exploratory efficacy endpoints The exploratory efficacy endpoints of this study include the following evaluations in adults with diabetic gastroparesis: ● The effect of dudonperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline gastroparesis, based on the mean ANMS GCSI-DD abdominal distension subscale score over the last two weeks of the 12-week treatment period, compared to placebo. ● Change from baseline with each dose of dudomperidone compared to placebo after 12 weeks of treatment in PAGI-QoL patients. ● Change from baseline with each dose of dudomperidone compared to placebo after 12 weeks of treatment in the GERDQ. ● Characterization of the absorption of dudomperidone under stable conditions and the concentration of its primary metabolites. ● Characterization of the exposure-response relationship of dudonperidone, as well as various measurements of efficacy and / or safety, may also be performed.

[0088] (iv)ANMS GCSI-DD questionnaire The ANMS GCSI-DD questionnaire targets five major gastroparesis-related symptoms: nausea, early satiety, postprandial bloating, epigastric pain, and vomiting. Bloating is included as an exploratory symptom. Symptoms are assessed using a numerical severity scale from 0 (none) to 4 (very severe). Vomiting is captured using a frequency scale and scored as follows: 0 for no episodes, 1 for one episode, 2 for two episodes, 3 for three episodes, and 4 for four or more episodes.

[0089] Participants will be instructed to complete the ANMS GCSI-DD questionnaire daily from screening, during the ANMS GCSI-DD baseline period, on the day of randomization, and daily from day 1 to day 84 (±4 days). Materials will be distributed at the screening visit. Adherence to the ANMS GCSI-DD will be assessed at the time of randomization (day 1), and participants must be at least 75% or receive approval from the sponsor to be eligible for the trial. The questionnaire should be completed at approximately the same time each evening.

[0090] Participants are instructed to complete a questionnaire that assesses their severity and vomiting episode response, representing the worst-case severity of symptoms over the 24 hours prior to the administration of emergency medication.

[0091] The daily ANMS GCSI-DD total symptom score is calculated by adding the scores of each of the five symptom items and then dividing by 5. Therefore, the maximum total symptom score can be 4 (5 symptoms × maximum score 4 = 20, 20 ÷ 5 = 4). The baseline for the analysis of ANMS GCSI-DD total scores and subscale scores is based on the mean weekly scores from 7 to 14 days prior to randomization. Both ANMS GCSI-DD total scores and subscale scores are analyzed to compare symptom scores between treatment groups.

[0092] (v) PGIS and PGIC The PGIS assessment will be conducted weekly, starting from the first visit. The PGIS will be performed at the third visit, prior to the first dose of the study drug, and this will serve as the baseline. The PGIS is a single-item scale completed at each visit to assess the current overall severity over the past seven days. The PGIS is assessed using a 5-point numerical scale. The PGIC assessment will be conducted at the fourth, fifth, sixth, and seventh visits. The PGIC is a single-item scale completed at each visit to assess the change in gastroparesis symptoms since the start of the study drug. The PGIC is assessed using a 5-point numerical scale.

[0093] (vi) PAGI-QoL equipment survey The PAGI-QoL questionnaire will be completed at the clinic during the first, third, fourth, fifth, sixth, and seventh visits prior to the initial administration of the investigational drug. The PAGI-QoL consists of 30 questions that inquire about the impact of some of the gastrointestinal problems the subject may be experiencing on their overall quality of life and well-being.

[0094] (vii) Gastroesophageal reflux disease questionnaire The GERDQ should be completed at the clinic during the first, third, fourth, fifth, sixth, and seventh visits prior to the initial administration of the investigational drug. The GERDQ assesses the patient's symptoms during the previous week. The GERDQ score is the sum of the individual question scores, ranging from 0 to 18.

[0095] (viii) Pharmacokinetics PK samples are collected according to Tables 1A and 1B. Plasma concentrations of dudomperidone and its primary metabolites are measured and used to estimate the following parameters. ● Stable state C based on samples taken after administration at the 5th visit in the initial PK subset. max . ● Steady-state trough concentration based on samples taken before medication administration at the 5th and 7th visits.

[0096] (ix)PGx rating For those participating in the optional PGx evaluation, blood samples will be collected at any point during the treatment period.

[0097] PGx samples may be used in genetic studies to explore the underlying causes of variability and / or differences in responses in PK, PD, and / or safety data after administration of dudomperidone. Participants will be given the option to participate in PGx evaluation during the study consent process.

[0098] F. Safety Evaluation The safety of dudonperidone will be evaluated from the time of informed consent to the end of the follow-up period. All safety endpoints will be summarized descriptively. Safety endpoints include: ● Incidence of clinically significant changes in laboratory parameters, physical examination findings, 12-lead ECG parameters, body weight, and vital signs. ● TEAE. ● SAEs that occur under treatment. ● TEAEs can cause premature discontinuation of the test drug. ● Significant laboratory abnormalities that occurred during treatment.

[0099] Example 2: A randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of dudonperidone in adult patients with diabetic gastroparesis. Summary: The objective of this clinical trial is to evaluate whether the investigational drug, dudonperidone, may help alleviate symptoms associated with diabetic gastroparesis in adult patients.

[0100] The main questions for which we seek answers are as follows: ● To evaluate the efficacy of dudomperidone compared to placebo for the symptoms of gastroparesis when administered to patients with diabetic gastroparesis. ● To evaluate the safety and tolerability of dudomperidone when administered to patients with diabetic gastroparesis compared to placebo.

[0101] Participants will complete the following schedule. ● Screening period (1-2 visits) ● Implementation period (one visit) ○ To assess eligibility for participation in the continuing study, complete the diary and other patient-reported outcomes (PROs) as described in the protocol. ● 12-week treatment period (5 visits) ○ Take the test drug orally twice a day. ○ Complete the log and other PROs as described in the protocol. ○ 1-week follow-up (1 visit to the clinic)

[0102] Researchers will compare the effects of the following treatments. ● Drug = Dudomperidone Dosage 1 ● Drug = Dudon Peridone Dosage 2 ● Drug = Placebo

[0103] Test design Trial type: Intervention Estimated registered participants: 400 Assignment: Randomization Intervention model: Parallel allocation Masking: Quadruple (Participant, Care Provider, Principal Investigator, Outcome Evaluator) Main purpose: Treatment

[0104] Treatment group and intervention TIFF2026511098000011.tif32170

[0105] Evaluation items Primary evaluation criteria: 1. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline, based on a composite score of the mean ANMS GCSI-DD nausea subscale and vomiting subscale scores [Time frame: last two weeks of a 12-week treatment period compared to baseline]

[0106] Secondary evaluation criteria: 1. Safety of dudonperidone [Time frame: Study participation period] ● The incidence of clinically significant changes in researchers' opinions, laboratory parameters, physical examination findings, 12-lead ECG parameters, body weight measurements, and vital signs measurements. ● TEAE. ● SAEs that occur under treatment. ● TEAEs can cause premature discontinuation of the test drug. ● Significant laboratory abnormalities that occurred during treatment. 2. Estimation based on a composite score of mean ANMS GCSI-DD nausea subscale and vomiting subscale scores using PGIS and PGIC as anchor subscales [Time frame: last two weeks of a 12-week treatment period] 3. Percentage of subjects with a history of lack of response showing a composite score reduction of more than 30%, or who were unable to tolerate metoclopramide therapy or other exercise stimulants [Time frame: last two weeks of the 12-week treatment period compared to baseline] Mean ANMS GCSI-DD nausea subscale score and vomiting subscale score composite score 4. Percentage of subjects identified as responders, defined as a mean decrease of 0.5 or more from baseline in the ANMSGCSI-DD nausea subscale score and vomiting subscale score [Time frame: last two weeks of the 12-week treatment period] 5. Percentage of patients who achieved a 30% or greater reduction in the mean composite score of the ANMS GCSI-DD nausea subscale and vomiting subscale from baseline [Time frame: last two weeks of the 12-week treatment period] 6. Percentage of patients who achieved a mean 30% or greater reduction in the ANMS GCSI-DD vomiting subscale score from baseline [Time frame: last two weeks of the 12-week treatment period] 7. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline [Time frame: last two weeks of the 12-week treatment period compared to baseline] Based on mean ANMS GCSI-DD nausea subscale score 8. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms compared to baseline [Time frame: last two weeks of the 12-week treatment period compared to baseline] Based on mean ANMS GCSI-DD vomiting subscale scores 9. Percentage of patients who achieved a mean reduction of 30% or more in the ANMS GCSI-DD nausea subscale score from baseline [Time frame: last two weeks of the 12-week treatment period] 10. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms [Time frame: last two weeks of the 12-week treatment period compared to baseline] Based on the average ANMS GCSI-DD total score 11. Percentage of subjects who achieved a mean reduction of 30% or more in the ANMS GCSI-DD total score [Time frame: last two weeks of the 12-week treatment period compared to baseline] 12. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms [Time frame: last two weeks of the 12-week treatment period compared to baseline] Based on mean ANMS GCSI-DD early satiety subscale scores 13. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms [Time frame: last two weeks of the 12-week treatment period compared to baseline] Based on mean ANMS GCSI-DD postprandial bloating subscale scores 14. The effect of dudomperidone on significantly reducing the severity of gastroparesis-related symptoms [Time frame: last two weeks of the 12-week treatment period compared to baseline] Based on mean ANMS GCSI-DD upper abdominal pain subscale scores 15. Percentage of symptom-free days for each dose of dudomperidone in the ANMS GCSI-DD total score, composite score of nausea and vomiting scores, nausea score, vomiting score, early satiety score, postprandial bloating score, and upper abdominal pain score [Time frame: last two weeks of the 12-week treatment period] On days when symptoms are present, the condition is defined as mild (ANMS GCSI-DD score > 2). 16. All of the above endpoints [Time frame: the last 6 weeks of the 12-week treatment period] 17. Changes in PGIS with each dose of dudonperidone [Time frame: from baseline to week 12] 18. Changes in PGIC with each dose of dudonperidone [Time frame: from baseline to week 12]

[0107] Eligibility Criteria Main selection criteria: ● Must be a male or female aged 18 or older. ● Diagnosed with type 1 or type 2 diabetes according to the criteria of the American Diabetes Association. ● Currently, I am diagnosed with diabetic gastroparesis as defined below. a. Gastrointestinal symptoms perceived to be consistent with gastroparesis within 6 months prior to screening, and b. You have recorded delayed gastric emptying within the past two years, or you are willing to complete a gastric emptying breath test. ● 18~45kg / m 2Body Mass Index (BMI) (including both ends). ● Glycosylated hemoglobin (HbA1c) level of less than 10% at the time of screening. ● I would like to discontinue the medication I am currently receiving for gastroparesis.

[0108] Main exclusion criteria: ● The cause of gastroparesis other than diabetes is known (e.g., idiopathic gastroparesis and / or gastroparesis resulting from surgery, viral disease, cancer, scleroderma, or other neurological disorders). ● A history or evidence of clinically significant arrhythmia. A history of pyloroplasty, pyloric myotomy, or gastroscopy / oral myotomy, fundoplication, gastrectomy, vagus nerve sectioning, or bariatric surgery. ● Currently receiving parenteral nutrition, or having a nasogastric or other enteral tube for nutritional support or pressure relief. ● Pyloric injection of botulinum toxin within 6 months of screening. ● Tested positive for drug abuse. ● Women who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the trial period.

[0109] Example 3 A. Test Objectives (i) Main purpose The primary efficacy objective of this study was to evaluate the ability of dudomperidone to significantly reduce gastroparesis-related symptoms in adult patients with diabetic gastroparesis compared to baseline, compared to placebo, based on a composite score of the mean ANMS GCSIDD nausea subscale and vomiting scale scores over the last two weeks of a 12-week treatment period.

[0110] (ii) Secondary purposes The secondary efficacy objective of this study is to evaluate the effect of dudonperidone compared to placebo on the following parameters in adult subjects with diabetic gastroparesis. ● Percentage of respondents showing a mean reduction of 0.5 or more from baseline in the ANMS GCSI-DD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period. ● Percentage of patients who achieved a 30% or greater reduction in their ANMS GCSI-DD nausea subscale score and vomiting score from baseline during the last two weeks of the 12-week treatment period. ● Percentage of symptom-free days in the ANMS GCSI-DD total score, nausea subscale score, and vomiting score composite score, as well as the subscale scores, over the last two weeks of the 12-week treatment period. ● Relationship between ANMS GCSI-DD nausea subscale scores and vomiting scores over a 12-week treatment period, and patient global impression of severity (PGIS) and patient global impression of change (PGIC). ● Percentage of subjects who showed clinical improvement in symptoms of gastroparesis, based on the average composite score of ANMS GCSI-DD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period, had a history of lack of response, or were unable to tolerate metoclopramide therapy or other motility enhancers such as erythromycin, neostigmine, or bethanechol. ● The effect of dudonperidone on significantly reducing gastroparesis-related symptoms compared to baseline, based on mean ANMS GCSI-DD total score and subscale scores over the last two weeks of a 12-week treatment period. ● Change in the mean composite score of ANMS GCSI-DD nausea subscale score and vomiting score from baseline over the last two weeks of a 12-week treatment period in subjects receiving glucagon-like peptide-1 receptor agonists (GLP-1RAs). ● Percentage of respondents taking GLP-1RAs who showed a mean reduction of 0.5 or more from baseline in the ANMS GCSI-DD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period. ● Percentage of patients taking GLP-1RAs who achieved a 30% or greater reduction in their ANMS GCSI-DD nausea subscale score and vomiting score from baseline during the last two weeks of a 12-week treatment period. ● Changes in ANMS GSCI-DD total score and composite symptoms related to gastroparesis from baseline to the last two weeks of the 12-week treatment period in subjects receiving GLP-1RA. ● All of the above primary and secondary objectives, which were evaluated during the last two weeks of the 12-week treatment period, will also be evaluated during the last six weeks of the 12-week treatment period. ● Changes from the PGIS baseline. ● Changes from PGIC baseline.

[0111] Secondary safety objectives include evaluating the safety of dudonperidone compared to placebo in adults with diabetic gastroparesis.

[0112] (iii) exploratory purpose; The exploratory efficacy objective of this study is to evaluate dudomperidone compared to placebo in adults with diabetic gastroparesis for the following: ● Percentage of patients showing a mean decrease of 0.5 or more from baseline in the ANMS GCSI-DD total score and subscale scores during the last two weeks of the 12-week treatment period, and during the last six weeks of the 12-week treatment period. ● Percentage of patients who achieved a reduction of 30% or more from baseline in their ANMS GCSI-DD total score and subscale scores during the last two weeks of the 12-week treatment period, and during the last six weeks of the 12-week treatment period. ● Estimates based on mean ANMS GCSI-DD total score and subscale score using PGIS and PGIC as anchors over a 12-week treatment period. ● The effect of dudonperidone on significantly reducing gastroparesis-related symptoms compared to baseline, based on the mean ANMS GCSI-DD vomiting subscale score. ● Changes from baseline in the Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QoL) using a medical device. ● Changes from baseline in the Gastroesophageal Reflux Disease Questionnaire (GERDQ). ● Changes in hemoglobin A1c (HbA1c), insulin requirements, and diabetes medication status from baseline to week 12. ● Changes in gastric emptying from baseline to week 12. ● Percentage of days spent using any emergency medication and its effect on the number of days used. ● The primary and secondary objectives related to the evaluation of the ANMS GCSI-DD vomiting score are to conduct exploratory analyses of vomiting severity. ● Characterization of the absorption of dudomperidone and the concentration of its primary metabolites under stable conditions. ● Characterization of the exposure-response relationship of dudonperidone, as well as various measurements of efficacy and / or safety, may also be performed.

[0113] B. Explanation of the exam (i) Overview of the test design This study is a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of dudonperidone in adults with diabetic gastroparesis after 12 weeks of treatment. See Figure 1.

[0114] The safety of dudomperidone will be evaluated from the time of informed consent to the end of the follow-up period. Participants will be tracked for efficacy and adherence to the study drug throughout the double-blind treatment period. Plasma concentrations of dudomperidone will also be measured at elective visits during the double-blind treatment period.

[0115] The total duration of the trial is approximately 18 weeks, including a screening and induction period of less than 5 weeks, a 12-week double-blind treatment period, and a follow-up period of up to 1 week. During participation, participants will complete 8 visits.

[0116] Informed consent will be provided, and after completing the screening and introductory periods, eligible subjects will be randomized in parallel to one of three treatment groups in a 1:1:1 ratio over a 12-week period. ● Dudomperidone 15 mg is administered as a single 10 mg capsule and a single 5 mg capsule in a BID (Bio-Injection) regimen; ● Dudomperidone 10 mg is administered as a single 10 mg capsule of dudomperidone and a single placebo capsule in a BID (Bio-Injection) regimen; or ● Dudomperidone placebo was administered as two matching placebo capsules in a BID (Bio-Injection) regimen.

[0117] Approximately 400 subjects (133 subjects per treatment group) will be randomized, and 363 subjects are expected to complete a 12-week double-blind treatment period. Subjects will be stratified by their birth sex (female, male) and their mean baseline composite score of the ANMS GCSI-DD nausea subscale and vomiting severity score (≤2.6 vs. >2.6).

[0118] Pharmacokinetics All targets: ● All participants in the study will have trough PK samples taken at their 5th and 7th visits. Trough samples should be taken within 60 minutes prior to administration of the study drug, if applicable. Only participants in PK subset B will be required to receive the drug at their 7th visit. ● Participants will be instructed to record the date and time of each administration two days before their 5th and 7th visits, and not to take the test drug at home on those visit days. ● Record the exact date and time of administration immediately before sampling each of these samples, and record the exact date and time for each PK sample. ● In the event of a serious adverse event (SAE) or adverse event (AE) leading to discontinuation of treatment, efforts should be made to collect a PK sample as quickly as possible. The date and time of the last administration of the test drug before the PK sample and the date and time of the PK sample should be recorded.

[0119] PK Subset A: ● Participants may choose to participate in PK subset A, where PK samples are collected only at the fifth visit after administration. ● Subjects should fast for at least 8 hours before this visit. However, to ensure the safety of the subjects, if it is determined that a subject should consume food (for example, due to hypoglycemia or symptoms of hypoglycemia), breakfast may be consumed more than 2 hours before and / or more than 3 hours after the morning administration of the study drug. The time of the subject's last meal before administration should also be recorded. ● PK blood samples should be collected within 60 minutes before administration of the test drug. ● Participants will remain at the clinic for a maximum of 3 hours after morning administration of the test drug, and blood samples will be collected approximately 1 hour and 2 hours after administration. If a participant wishes to remain at the clinic longer and is able to do so, a PK sample will also be collected approximately 3 hours after administration. ● If the subject wishes to remain at the clinic or return to the clinic, additional samples may be collected within the following post-administration window on the same day. ○ 4-8 hours, and / or ○ 8~12 hours. ● Participants were instructed to record the date and time of each administration two days prior to these visits, and not to take the test drug at home on the day of the visit. Post-administration PK samples were to be collected within ±15 minutes of the nominal time. The exact date and time of administration of the test drug and each PK sample on the day of the visit were also to be recorded. ● After approximately 30 participants in PK subset A have completed their fifth visit, new blinded PK and safety data will be evaluated for each participant assignment to determine the dosage level to be carried over for the remainder of the study. Enrollment in PK subset A may continue after the review. Participants may also choose to participate in PK subset B, as described below.

[0120] PK Subset B: ● Once the initial data review from PK subset A is complete, a new subset of subjects may choose to participate in PK subset B, in which subjects will provide post-administration samples collected at the 5th, 6th, and / or 7th visits. ● For the 5th and 7th visits, subjects should fast for at least 8 hours. However, to ensure the subject's safety, if it is determined that the subject should consume food (e.g., due to hypoglycemia or symptoms of hypoglycemia), breakfast may be consumed more than 2 hours before and / or more than 3 hours after the morning administration of the study drug. On the day of the 6th visit, subjects may take the study drug at home. For each of these visits, the time of the subject's last meal before medication administration should also be recorded. ● PK blood samples should be collected within 60 minutes before administration of the test drug (only during the 5th and 7th visits) and at one of the following post-administration windows during the 5th, 6th, or 7th visit. ○ 1-4 hours, and / or ○ 4-8 hours, and / or ○ 8~12 hours. For subjects who wish to provide post-administration samples at two or more of the designated visits (5th, 6th, and 7th visits), the post-administration samples should be within different time windows. For example, if a subject provides a post-administration sample within a 1-4 hour window at the 5th visit, the subject should provide a sample within a 4-8 hour or 8-12 hour window at a subsequent visit (6th or 7th visit). If a subject chooses to provide post-administration PK samples at all three visits, and the sample at the 6th visit is taken between 8 and 12 hours after administration, the sample at the 7th visit should be taken between 4 and 8 hours after administration. ● For subjects who choose to provide two or more post-administration samples, efforts will be made to collect each sample within different timeframes. Subjects will be instructed to record the date and time of each administration two days prior to their visit, and not to take the study drug at home on the 5th and / or 7th visit. Post-administration PK samples will be collected within ±15 minutes of the nominal time. The exact date and time of administration of the study drug and each PK sample on the day of the visit will also be recorded.

[0121] interim analysis Following the PK subset A evaluation, a re-estimation of the blinded sample size may be performed. This analysis is to ensure that the common standard deviation of the primary efficacy endpoint does not deviate significantly from the original assumptions used in the sample size and power calculations. The blinded analysis will not discontinue the study due to efficacy or futility. Since the analysis is based on blinded data, the type 1 error rate is strongly controlled as a result of this blinded data review, and no final alpha adjustment is required.

[0122] During the trial, a single blinded interim analysis (IA) will be conducted after approximately 50% of the randomized participants have completed their end-of-treatment (EOT) visit or have discontinued treatment early.

[0123] Overall test design and procedure At the screening visit, all participants will provide informed consent before any protocol-specific procedures are performed. Participants must meet all inclusion criteria and not meet exclusion criteria to be eligible to participate in the study.

[0124] Except when GEBT is described and the target group is selected as a PK subset, an overnight fast is not required.

[0125] The subjects are evaluated as follows: ● Screening period (first visit, -35 days to -22 days): ○ A screening procedure will be implemented, and participants will begin washing out any applicable excluded medications. Participants are required to wash out all prohibited medications for at least 14 days or 5 half-lives (whichever is longer) before the start of the ANMS GCSI-DD baseline period (defined as the 14 days prior to randomization) and / or before GEBT is performed at the second visit. ○ At the start of the screening visit, the patient's ANMS GCSI-DD, PAGI-QoL, GERDQ, PGIS, and use of acceptable emergency medications will be recorded. ● Implementation period (second visit, -21 days to -1 day): In addition to clinic visits during this period, telephone visits can be completed to assess adherence to the patient's journal, concomitant treatments, and adverse events (AEs). If the patient requires additional assessments that necessitate further clinic visits, the patient may report to the clinic any additional procedures corresponding to the scheduled outpatient visit. ○ Participants are required to complete the ANMS GCSI-DD questionnaire daily and to record the use of acceptable emergency medications daily. ○ The mean of daily ANMS GCSI-DD measurements obtained over 14 days prior to randomization constitutes the "baseline" measurement. ○ GEBT: Ideally, the GEBT should be performed on one day between day -21 and day -12, but it may be performed outside this window if there is sufficient time for GEBT analysis before randomization. The GEBT should be performed after a washout of at least 14 days or 5 half-lives (whichever is longer). Participants should fast for at least 8 hours before the GEBT and for 4 hours after the GEBT meal. Participants who actively use nicotine-containing products must refrain from using these products from the time they wake up in the morning of the GEBT until the completion of the study. The GEBT should be standardized. 13Breath samples were taken twice before the intake of the C-fortified meal, and then at 45, 90, 120, 150, 180, and 240 minutes after meal intake. The meal should be consumed within 10 minutes. Fasting blood glucose was assessed before the GEBT to confirm a blood glucose level of <275 mg / dL. If a subject's fasting blood glucose level was ≥275 mg / dL despite the use of corrective insulin, the GEBT would not be performed. During the induction period, subjects were permitted to return to the clinic within 1-3 days to complete the study, or they may be excluded from the study if they no longer met stable, well-controlled blood glucose standards. On the day of the GEBT, subjects should visit the clinic after an overnight fast and take their regular medications (including any diabetes treatments), except for prohibited concomitant medications. Subjects requiring insulin will self-administer their usual morning insulin injection, taking their fasting status into consideration. Subjects will be instructed to bring insulin to the clinic as needed. Fasting blood glucose was assessed before gastric emptying evaluation to confirm a blood glucose level of <275 mg / dL. Additional insulin was administered (titrated based on meal calorie intake) to confirm a blood glucose level of <275 mg / dL before the gastric emptying procedure. Hypoglycemia (hypoglycemia, blood glucose level <60 mg / dL) should be managed. While baseline GEBT is preferably performed during the induction period (second visit, -21 to -12 days), baseline GEBT may be performed outside the -21 to -12 day window as described, provided that the trial is conducted on a day prior to the expected randomization date that will allow adequate time for GEBT analysis. If, at the first visit, the subject arrives at the clinic, is not taking any exclusion medications, and meets all the required criteria specified in the protocol (e.g., minimum 8 hours of fasting, glucose level <275 mg / dL, etc.), the procedures for the first and second visits may be performed on the same day. ● 12-week double-blind treatment period (3rd visit to 7th visit, days 1 to 84): ○ Adherence to ANMS GCSI-DD will be assessed at the time of randomization (Day 1), and a rate of 75% or higher is required to be eligible for the trial. ○ The investigational drug (dudonperidone and / or placebo capsules) will be administered for 84 (±4) days, and a safety evaluation will be conducted. ○ Record the use of acceptable emergency medications daily. ○ The ANMS GCSI-DD questionnaire should be completed at approximately the same time each evening. ○ Complete the PAGI-QoL and GERDQ at the clinic during the third visit prior to the first administration of the investigational drug, as well as during the fourth, fifth, sixth, and seventh visits. ○ All subjects participating in the study will have trough PK samples taken at their 5th and 7th visits. Trough samples should be taken within 60 minutes prior to administration of the study drug, if applicable. Only subjects participating in PK subset B will be required to receive an administration at their 7th visit. Subjects will be instructed to record the date and time of each administration two days prior to their 5th and 7th visits, and not to take the study drug at home on those visit days. The exact date and time of the administration immediately preceding the collection of each sample should be recorded, and the exact date and time of each PK sample should be recorded. ○ PK Subset A: Participants may choose to participate in PK subset A, where post-administration PK samples are collected only at the fifth visit. PK blood samples should be collected within 60 minutes prior to administration of the study drug. Participants will remain at the clinic for up to 3 hours after morning administration of the study drug, and blood samples will be collected approximately 1 hour and 2 hours after administration. If a participant wishes to remain at the clinic longer and is able to do so, a PK sample will also be collected approximately 3 hours after administration. If a participant wishes to remain at the clinic or return, additional samples may be collected within the post-administration window (4-8 hours and / or 8-12 hours) on the same day. Participants will be instructed to record the date and time of each administration two days prior to these visits and not to take the study drug at home on these visit days. Post-administration PK samples should be collected within ±15 minutes of the nominal time. The exact date and time of administration of the study drug and each PK sample on the visit day should also be recorded. Enrollment in PK subset A may continue. The target may also choose to participate in PK subset B, as described below. ○ PK Subset B: Once the initial data review from PK subset A is complete, a new subset of subjects may choose to participate in PK subset B, in which subjects will provide additional post-administration samples at one or more post-administration windows of 1-4 hours, 4-8 hours, or 8-12 hours during their 5th, 6th, and / or 7th visits. For subjects who wish to provide post-administration samples at two or more of the designated visits (5th, 6th, and 7th visits), the post-administration samples should be within different windows. Subjects will be instructed to record the date and time of each administration two days prior to their 5th, 6th, and / or 7th visits, and not to take the study drug at home on the day of their 5th and / or 7th visits. Post-administration PK samples should be collected within ±15 minutes of the nominal time. The exact date and time of administration of the study drug and each PK sample on the day of the visit should also be recorded. ○ Patients may choose to complete the additional GEBT performed at the 7th visit (EOT) / ET, and will comply with all the above requirements for GEBT during the induction period. If the patient's fasting blood glucose level is ≥275 mg / dL despite the use of corrective insulin, GEBT will not be performed at this visit or any future visit, and the remaining procedures will be completed to finish EOT. Safety will be assessed through evaluation of adverse events (AEs), vital signs, physical examination, clinical laboratory evaluation (chemistry, hematology, coagulation, urinalysis, and prolactin), and 12-lead electrocardiogram (ECG) findings. Furthermore, a single, optional pharmacogenetic (PGx) blood sample can be collected at any point during the treatment period. ● Follow-up period: (8th visit, 91st day [±3 days]): ○ Participants will be asked to make follow-up visits approximately one week (±3 days) after the last dose of the study drug to evaluate adverse events (AEs), changes in concomitant therapy (including the use of emergency medications), vital signs, 12-lead ECG, prolactin, chemistry, hematology, and coagulation.

[0126] Unscheduled visits and / or additional follow-up may be required. For example, patients with clinically significant abnormal laboratory findings, unresolved TEAEs, SAEs requiring follow-up examinations and reviews, or clinically significant AEs may require further evaluation.

[0127] C. Selection and cancellation of targets (i) Selection criteria Based on the screening evaluation, individuals who meet all of the following criteria are eligible to participate in the examination. 1. Be a male or female aged 18 or older. 2. The person has been diagnosed with type 1 or type 2 diabetes according to the criteria of the American Diabetes Association. 3. Currently, the patient is diagnosed with diabetic gastroparesis as defined below. a. Gastrointestinal symptoms consistent with gastroparesis within 6 months prior to screening (e.g., postprandial nausea / vomiting, postprandial bloating, early satiety, abdominal distension, and / or epigastric / abdominal pain), and b. Recorded delayed gastric emptying, as determined by GEBT, scintigraphy, or manometry. An attempt should be made to obtain a medical history of gastric emptying; however, if this information is unavailable, this criterion can be met using a GEBT completed during the induction period. 4. 18-45 kg / m² at screening 2 It has a body mass index (BMI) that includes both ends. 5. The patient has an HbA1c level of 10% or less at the time of screening and has stable, well-controlled blood glucose levels. 6. If you are receiving treatment with a GLP-1RA, a trial may be considered if all of the following criteria are met. a. Participants have been taking a stable dose of GLP-1RA for at least 3 months prior to screening and are expected to maintain the same dose during the GEBT and throughout the study; b. Sufficiently resistant to GLP-1RA; c. None of the signs / symptoms of gastroparesis that qualify for the study (e.g., postprandial nausea / vomiting, postprandial bloating, early satiety, abdominal distension, or epigastric / abdominal pain) are attributable solely to the use of GLP-1RA; and d. Symptoms of gastroparesis appeared before the initiation of GLP-1RA therapy. 7. Male subjects with a female partner of potential pregnancy must agree to use two medically acceptable and effective methods of contraception from day 1 to day 90 after the last dose of the study drug. Medically acceptable and effective methods of contraception for male subjects with a female partner of potential pregnancy include the following: ○ Latex condoms containing spermicides, ○ Pessaries containing vaginal spermicides, ○ Cervical cap containing spermicide, ○ Indwelling intrauterine contraceptive device (hormonal or non-hormonal), ○ Contraceptive implants, ○ Oral contraceptives, and ○ Vasectomy (if performed at least 6 months prior to administration of the study drug). 8. Male participants must agree to refrain from donating sperm from day 1 to day 90 after the final dose of the study drug. 9. Female subjects with a male partner must be either surgically infertile (hysterectomy and / or bilateral oophorectomy), postmenopausal (defined as a woman aged 50 or older who has had spontaneous amenorrhea for at least one year and whose follicle-stimulating hormone levels are in the postmenopausal range at the time of the screening visit, based on the laboratory range), or consent to use one of two medically acceptable effective contraception methods from 14 to 60 days after the last dose of the study drug. Medically acceptable effective contraception methods for female subjects with a male partner include: ○ Latex condoms containing spermicides, ○ Pessaries containing vaginal spermicides, ○ Cervical cap containing spermicide, ○ Indwelling intrauterine contraceptive devices (hormonal and non-hormonal), ○ Vasectomy in the male partner (if performed at least 6 months prior to administration of the study drug), ○ Contraceptive implants or oral contraceptives. 10. I am willing to and able to refrain from taking plumlintide from screening to end-of-treatment (EOT). 11. You understand and can abide by all trial visits, procedures, restrictions, and discontinuation of medications (including those for treating gastroparesis) (as specified in the protocol), and you can provide written informed consent in accordance with institutional and regulatory guidelines.

[0128] (ii) Exclusion criteria Individuals who meet any of the following criteria will be excluded from participating in the examination. 1. The primary cause of gastroparesis other than diabetes is known (e.g., idiopathic gastroparesis, surgery, viral disease, cancer, scleroderma, or gastroparesis resulting from other neurological disorders). 2. The patient has been hospitalized within the past year prior to their first visit for diabetic gastroparesis and / or diabetic ketoacidosis. 3. The patient has a history or current history of clinically significant arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsades de pointes. 4. Having evidence (based on screening or baseline assessment) or a history of clinically significant immunological, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies); surgical conditions; cancer (excluding basal cell carcinoma or squamous cell carcinoma of the skin, and cancers that have resolved or been in remission for >5 years prior to the screening visit); any condition that may significantly interfere with the absorption, distribution, metabolism, or excretion of the study drug. Cholecystectomy and appendectomy are permitted if the procedure was performed >6 months prior to screening. 5. The patient has a history of a prolactin-releasing pituitary tumor (e.g., prolactinoma). 6. Having known or suspected hypogonadism, current clinically significant menstrual abnormalities (e.g., oligomenorrhea or amenorrhea), gynecomastia, galactorrhea, or other clinical features that may be consistent with hyperprolactinemia. 7. You have received a pyloric injection of botulinum toxin within 6 months of screening, and / or are scheduled to receive an injection during the study. 8. The patient has a history of pyloroplasty, pyloric myotomy, or gastrointestinal endoscopic myotomy. 9. At the time of screening, the patient has total bilirubin, alkaline phosphatase, AST, or ALT levels >2×ULN, or has a Child-Pugh classification grade of B or C. 10. Use the Chronic Kidney Disease Epidemiology Collaboration formula during screening, with a threshold of <30 mL / min / 1.73 m 2 It has an estimated glomerular filtration rate. 11. Abnormal thyroid-stimulating hormone levels are present at the time of screening. 12. The subject is unable to undergo a GEBT or has a fasting blood glucose level of ≥275 mg / dL on the day of the baseline GEBT (second visit). If the subject's fasting blood glucose level is ≥275 mg / dL despite the use of corrective insulin, the GEBT will not be performed. During the initiation period, the subject may be permitted to return to the clinic within 1-3 days to complete the baseline GEBT trial, or the subject may be excluded from the trial if they no longer meet the criteria for stable, well-controlled blood glucose (selection criterion 5). Subjects actively using nicotine-containing products must refrain from using these products from the morning of the GEBT until the completion of the trial. 13. The patient has a known allergy to eggs or spirulina. 14. Use investigational drugs, prescription drugs, or over-the-counter drugs as follows: a. Actively participating in an experimental therapy trial. Received experimental therapy with a small molecule within 30 days of randomization or within 5 half-lives (whichever is longer), or received experimental therapy with a large molecule within 90 days of randomization or within 5 half-lives (whichever is longer). b. Regarding CYP3A4 inhibitors and inducers (drugs, herbal supplements, dietary supplements, nutraceuticals, or foods): ■ For subjects who choose to provide pharmacokinetic (PK) samples exceeding trough levels at the 5th and 7th visits, all CYP3A4 inhibitors and / or inducers within 14 days of the initial administration of the study drug or within 5 half-lives (whichever is longer) will be excluded until the end of the study. ■ For all other subjects, all CYP3A4 inhibitors and / or inducers within 14 days of the first dose of the study drug or within 5 half-lives (whichever is longer) will be excluded until the end of the study. Weak and moderate CYP3A4 inhibitors and inducers are acceptable. ■ For all participants, the use of grapefruit, grapefruit products, starfruit products, and Seville oranges is prohibited from 48 hours before randomization until the end of treatment (EOT). c. Avoid the use of motility stimulants (including, but not limited to, metoclopramide, domperidone, erythromycin, and pyridostigmine), other drugs and medications that may affect gastric emptying (e.g., all anticholinergics), and antiemetics (except protocol-specified emergency antiemetics) within 7 days prior to the baseline GEBT (second visit) and / or within 5 half-lives prior to the start of the ANMS GCSI-DD baseline period (defined as the 14 days prior to randomization), and until the end of the study. d. Regularly scheduled or anticipated opioid use during the course of participation in the study. During the treatment period of the study, prescribed non-sustained-release opioids for up to 72 hours are permitted. If any subject is taking opioids prior to GEBT, the opioids must be interrupted for at least 72 hours or 5 half-lives (whichever is longer) before the start of GEBT. e. Daily use of marijuana and / or tetrahydrocannabinol (THC)-containing products. Subjects who do not daily use THC may be considered for testing if product use is for medical reasons as described in Exclusion Criterion 15. f. Use of different doses of antidepressants, anxiolytics, antipsychotics, or prescription sleep medications in the three months prior to screening. g. Any drug, herbal supplement, dietary supplement, or nutraceutical known to cause QT prolongation within 28 days prior to the first dose of the study drug before the end of the study. 15. A positive drug or alcohol test result at screening without medical explanation, or a history of alcohol dependence or drug abuse as defined in the Diagnostic and Statistical Manual of Mental Disorders (4th edition) within two years prior to screening, and / or consuming 14 or more alcoholic beverages per week. One alcoholic beverage is equivalent to 1 / 2 pint beer (285 mL), one glass of spirits (25 mL), or one glass of wine (125 mL). If a false positive is suspected, a confirmatory test for drugs or alcohol may be performed using a different method. Cotinine is tested only at screening. Subjects showing a positive test result for THC at their first visit may be eligible to continue the study, provided they have a prescription for the drug and agree to avoid daily use of THC-containing products during their participation in the study. Subjects practicing a stable regimen of non-daily use must agree to refrain from prescribed marijuana and / or THC-containing products for at least 24 hours prior to GEBT. The frequency of use must be clearly understood at the clinic and recorded in the information source. Cotinine is non-exclusive, and subjects showing a positive test result for cotinine are eligible to continue the study. Subjects who actively use nicotine-containing products should maintain a nearly constant frequency of use during the study, except on GEBT days, on GEBT days, subjects must refrain from using these products from the time they wake up on the morning of the GEBT until the study is completed. 16. Possesses evidence of ongoing illegal recreational drug use. 17. The patient has a known history of an eating disorder or an ongoing eating disorder within two years of the screening visit. 18. At the time of screening, the patient is positive for human immunodeficiency virus antibody, hepatitis C virus antibody using confirmatory RNA, or hepatitis B surface antigen. 19. Are you currently receiving treatment with weight-loss medication, or have you had weight-loss surgery in the past (e.g., gastric bypass surgery)? 20. You are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the examination. 21. Unable to swallow medication. 22. Currently receiving parenteral nutrition, or having a nasogastric or other enteral tube (e.g., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ] tube) for nutritional support or decompression. 23. Having known or suspected gastric outflow tract obstruction (e.g., peptic stenosis) or other mechanical obstruction of the gastrointestinal tract, as recorded by upper gastrointestinal endoscopy or upper gastrointestinal X-ray series within the past two years. 24. Having a known history or current diagnosis of intestinal malabsorption or exocrine pancreatic disease. 25. A history of severe constipation is defined as the occurrence of two of the following criteria in the past three months or more: no more than two spontaneous bowel movements per week (e.g., not induced by laxatives within 24 hours); 25% or more of the stool is lumpy and / or hard; 25% or more of the stool feels like it has not been completely emptied after a bowel movement; 25% or more of the time the patient strains during a bowel movement; and / or dependence on osmotic or stimulant laxatives (i.e., daily use). 26. Patients with a history of gastric surgery, such as fundoplication, gastrectomy, vagus nerve transection, pyloroplasty, or obesity treatment. Patients with a gastric pacemaker in appropriate location may have the pacemaker turned off at least 14 days before the start of the ANMS GCSI-DD baseline period and throughout the remainder of the study. A history of diagnostic endoscopy is not exclusionary. 27. Having any medical condition or mental disorder that could interfere with the conduct of the study or expose the subject to an unacceptable risk. 28. Lack of response to domperidone, or a history of known hypersensitivity or intolerance to domperidone or any excipient in dudomperidone formulations. 29. Inappropriate for any other reason that may increase the risk to the subject during participation or interfere with the interpretation of the study results.

[0129] (iii) Randomization criteria Participants who meet the following criteria will be randomized at their third visit (Day 1). 1. All selection / exclusion criteria remain met. 2. Participants should not have used any motility-enhancing agents (including, but not limited to, metoclopramide, domperidone, erythromycin, pyridostigmine), other drugs and medications that may affect gastric emptying (e.g., all anticholinergics), or antiemetics (except protocol-specified emergency antiemetics) within 7 days prior to the baseline GEBT (second visit) and / or within 5 half-lives prior to the start of the ANMS GCSI-DD baseline period (defined as the 14 days prior to randomization), and should refrain from using them until the end of the study. Participants meeting the criteria for GLP-1RA use (selection criterion 6) should not be required to discontinue GLP-1RA before the GEBT and should maintain their prescribed dose. Participants actively using nicotine-containing products must refrain from using these products from the morning of the GEBT until the end of the study. Participants must agree to refrain from using opioids for ≥72 hours or 5 half-lives prior to the GEBT (whichever is greater). Individuals practicing a stable regimen of non-routine use must agree to refrain from using prescribed marijuana and / or THC-containing products for at least 24 hours prior to a GEBT. 3. To demonstrate a definitive diagnosis of diabetic gastroparesis as defined below. a. Gastrointestinal symptoms consistent with gastroparesis within 6 months prior to screening (e.g., postprandial nausea / vomiting, postprandial bloating, early satiety, abdominal distension, and / or epigastric / abdominal pain), and b. During the induction period (ideally between day -21 and day -12, but may be conducted outside this window if there is sufficient time for GEBT analysis before randomization) 13 Recorded symptoms of delayed gastric emptying, such as those determined by C-spirulina platensis GEBT. The GEBT must include kPCD values ​​over a 240-minute period and should show the peak emptying occurring at 240 minutes (e.g., the maximum kPCD value occurs at 240 minutes) and / or kPCD values ​​at 90 minutes, 120 minutes, or 150 minutes that are below the respective standard cutoff values. 4. During the baseline period (i.e., 14 days prior to randomization) in which the subject was not taking exercise stimulants or antiemetics (excluding protocol-specified emergency medications), the subject had an ANMS GCSI-DD score that met the following criteria: a. Average weekly nausea subscale score of 2 or higher ("moderate" or higher), b. There are no days with a nausea subscale score of 0 ("none"), and c. At least one vomiting episode per week on average (of any severity). Vomiting (emesis) is clinically defined as the oral expulsion of gastrointestinal contents due to the contraction of the muscles of the intestines and the chest and abdominal wall, while reflux is defined as the effortless expulsion of stomach contents into the mouth. Participants should be taught the difference between vomiting and reflux, which are defined as the act of bringing swallowed food back into the mouth, and should record vomiting episodes accordingly. 5. Adherence to ANMS GCSI-DD during the baseline period, defined as 75% or higher adherence.

[0130] D. Experimental Therapy (i) Treatment group This trial will be designed to include three treatment groups, each containing 133 participants.

[0131] Informed consent will be provided, and participants who remain eligible after the screening and induction periods will be randomized in parallel to one of three treatment groups in a 1:1:1 ratio over 12 weeks: ● Dudomperidone 15 mg is administered as a single 10 mg capsule and a single 5 mg capsule in a BID (Bio-Injection) regimen; ● Dudomperidone 10 mg is administered as a single 10 mg capsule of dudomperidone and a single placebo capsule in a BID (Bio-Injection) regimen; or ● Dudomperidone placebo was administered as two matching placebo capsules in a BID (Bio-Injection) regimen.

[0132] (ii) Drug supply (a) Formulations and packaging Dudonperidone capsules consist of dudonperidone active ingredient in oval, blue, opaque softgel capsules of size 2C. Each dudonperidone softgel capsule contains either 10 mg or 5 mg of active dudonperidone active ingredient. The dudonperidone-filled formulations contain the inactive components listed in Table 4.

[0133] (Table 4) Inactive components of dudonperidone TIFF2026511098000012.tif29170

[0134] Corresponding placebo softgel capsules containing the same inactive ingredient (excluding dudonperidone active pharmaceutical ingredient) are also provided (Table 5).

[0135] (Table 5) Inactive components of placebo TIFF2026511098000013.tif29170

[0136] Softgel capsules (capsules containing the active ingredient dudomperidone and placebo capsules) are packaged in blister packs to obtain the required dose for the study.

[0137] (b) Administration of the test drug The randomized entire population takes one blinded dose of the test drug (dudgeon peridone and / or placebo capsules) orally BID with approximately 240 mL of water. For a given individual, maintain an interval of approximately 12 hours (e.g., 8:00 am to 8:00 pm) between each administration. Subjects are required to fast for 2 hours before and 1 hour after all administrations. Only subjects participating in PK subset B are required to take the dose at the 7th visit. Subjects in the PK subset who provide post-dose PK samples at the 5th, 6th, and / or 7th visits are required to fast for at least 8 hours before the morning dose of the test drug and for more than 3 hours after the dose of the test drug. However, to ensure subject safety, if it is determined that the subject should consume food (e.g., due to low blood sugar or symptoms of hypoglycemia), the subject may consume breakfast two hours ahead of, and / or more than three hours after, the morning dose of the test drug. Subjects who choose to complete the GEBT at the 7th visit are required to fast for at least 8 hours before the start of the GEBT meal or, if applicable, before the morning dose of the test drug, and for 4 hours after completion of the GEBT meal.

[0138] Subjects are provided with self-administered test drug doses that are not administered at the clinic.

[0139] If a subject forgets a scheduled dose and notices the missed dose within 2 hours of the scheduled dosing time, the subject should be instructed to take the assigned dose of the test drug at the time the subject becomes aware of the missed dose. If a subject notices that they did not take the dose more than 2 hours after the scheduled dosing time, the subject should be instructed to skip this dose of the test drug and resume the assigned dose of the test drug at the next scheduled time.

[0140] If the subject vomits after taking the scheduled dose of the investigational drug, the subject is instructed to note the time of investigational drug administration and the time of vomiting and to resume the assigned dose of the investigational drug at the next scheduled time. During the treatment period, the subject should record the time of vomiting in relation to the time of investigational drug administration and attempt to report this to the clinic staff during the scheduled hospital visit. For subjects selected for the PK subset, if the subject vomits within the first 4 hours after dosing and before the post-dose PK sampling at the hospital visit is completed, the PK sampling is aborted. However, the samples collected prior to vomiting are analyzed.

[0141] Subjects in the PK subset are instructed to record the date and time of each administration 2 days prior to the corresponding 5th, 6th, and / or 7th hospital visit and are instructed not to take the investigational drug at home on the 5th and / or 7th hospital visit days.

[0142] Record the administration of the investigational drug on the hospital visit day and the exact date and time of each PK sample.

[0143] (ii) Prior treatment and concomitant treatment and / or procedures (a) Excluded medications, foods, and / or procedures During the trial, the use of the following investigational drugs, prescription drugs, or over-the-counter drugs is not permitted. ● Pramlintide from screening to EOT. ● Different doses of GLP-1RA. ● Experimental therapy with small molecules received within 30 days or 5 half-lives (whichever is longer) of randomization or experimental therapy with macromolecules received within 90 days or 5 half-lives (whichever is longer) of randomization. ● For CYP3A4 inhibitors and inducers (any of drugs, herbal supplements, dietary supplements, nutraceuticals, or foods): ○ For subjects who choose to provide PK samples exceeding the trough sample at the 5th and 7th visits, all CYP3A4 inhibitors and / or inducers within 14 days of the initial administration of the study drug or within 5 half-lives (whichever is longer) up to the end of the study will be excluded. ○ For all other subjects, all CYP3A4 inhibitors and / or inducers within 14 days of the first dose of the study drug or within 5 half-lives (whichever is longer) up to the end of the study will be excluded. Weak and moderate CYP3A4 inhibitors and inducers are acceptable. ○ For all participants, the use of grapefruit, grapefruit products, starfruit products, and Seville oranges is prohibited from 48 hours before randomization until End-of-Trial (EOT). ● Drugs, herbal supplements, dietary supplements, or nutraceuticals known to cause QT prolongation within 28 days prior to the first dose of the study drug before the end of the study. ● Avoid the use of gastric motility stimulants (including, but not limited to, metoclopramide, domperidone, erythromycin, and pyridostigmine), other drugs and medications that may affect gastric emptying (e.g., all anticholinergics), and antiemetics (except protocol-specified emergency antiemetics) within 7 days prior to the baseline GEBT (second visit) and / or within 5 half-lives prior to the start of the ANMS GCSI-DD baseline period (defined as the 14 days prior to randomization), and refrain from using them until the end of the study. ● Regularly scheduled or anticipated opioid use during the course of participation in the study. During the treatment period of the study, prescribed non-sustained-release opioids for up to 72 hours are permitted. If any subject is taking opioids prior to GEBT, the opioids must be interrupted for at least 72 hours or 5 half-lives (whichever is longer) before the start of GEBT. ● Daily use of marijuana and / or THC-containing products. Subjects who do not use THC on a daily basis may be considered for testing if their use of the product is for medical reasons. Subjects who test positive for THC on their first visit may be eligible to continue the test, provided they have a prescription for the drug and agree to avoid daily use of THC-containing products during their participation in the test. Subjects who follow a stable regimen of non-daily use must agree to refrain from prescribed marijuana and / or THC-containing products for at least 24 hours prior to the GEBT. Frequency of use must be clearly understood at the clinic and recorded in the source. Cotinine is non-exclusive, and subjects who test positive for cotinine are eligible to continue the test. Subjects who actively use nicotine-containing products should maintain a nearly stable frequency of use during the test, except on the GEBT day, on the GEBT day, subjects must refrain from using these products from the time they wake up on the morning of the GEBT until the test is completed. ● Different dosages of antidepressants, anxiolytics, antipsychotics, or prescription sleeping pills. ● You are scheduled to receive a pyloric injection of botulinum toxin within 6 months of screening, and / or during the trial. ● Treatment with weight-loss medication, or past weight-loss surgery (e.g., gastric bypass surgery). ● Parenteral nutritional support, or the presence of a nasogastric or other enteral tube (e.g., PEG or PEJ tube) for nutritional support or decompression. ● Dependence on osmotic or stimulant laxatives (i.e., daily use). ● A gastric pacemaker that cannot be turned off for at least 14 days prior to the start of the ANMS GCSI-DD baseline period and throughout the remainder of the study.

[0144] Those requiring further treatment with prohibited substances may discontinue the study treatment and undergo follow-up study procedures.

[0145] (b) Restricted drugs and / or procedures Patients experiencing severe symptoms of gastroparesis may take promethazine (Phenergan®) 25 mg or ondansetron (Zofran®) 4 mg.

[0146] (c) Permitted drugs and / or procedures Weak and moderate inhibitors and inducers of CYP3A4 are permitted in subjects not participating in PK subsets.

[0147] Eligible patients are permitted to continue receiving a stable dose of GLP-1RA.

[0148] If a subject was taking a stable dose of antidepressant, anxiolytic, or prescription sleep medication more than three months prior to screening, they are permitted to continue taking these medications.

[0149] The patient may, if necessary, use a single dose of opioid (non-sustained-release formulations for up to 72 hours) during the treatment period for severe pain.

[0150] Other medications that have not been explicitly or previously excluded are permitted (e.g., emergency medications).

[0151] Antacids, histamine-2 receptor antagonists, and proton pump inhibitors should only be taken within ±2 hours of the time of administration of the study drug. These drugs may affect the oral bioavailability of dudomperidone.

[0152] (d) First aid Patients experiencing severe symptoms of gastroparesis may take either promethazine (Phenergan) 25 mg or ondansetron (Zofran) 4 mg orally, and may be prescribed topically as needed.

[0153] Patients should be encouraged to use over-the-counter ginger (e.g., in the form of capsules, soft chews, chewing gum, oil, or tea) up to 1000 mg once daily before using promethazine or ondansetron.

[0154] During the washout period (-35th day to -22nd day), subjects can take emergency medications as needed.

[0155] However, during the 3-week lead-in period (-21st day to -1st day), subjects experiencing severe symptoms of gastric hypoparesis can take only a single dose of either promethazine 25 mg, ondansetron 4 mg, or an over-the-counter ginger product once a day for 3 days a week.

[0156] During the ANMS GCSI-DD baseline period, subjects should be strongly encouraged to avoid emergency medications if possible and use them sparingly if used. If a subject uses emergency medications for more than 3 days a week and / or exceeds the 1-day limit of emergency medications as described above during the 14-day ANMS GCSI-DD baseline period, the subject can discontinue the trial at the time of review.

[0157] After randomization, the use of emergency medications is limited to a maximum of 3 days a week and 1 dose per day only if the subject experiences nausea and / or vomiting of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher. If a subject uses the emergency medication once a day for 3 days a week for two consecutive weeks and is confirmed by the clinic staff, the subject discontinues the investigational drug due to lack of efficacy but remains in the trial and is encouraged to continue with the remaining trial procedures and evaluations. These subjects are required to complete the ET visit and then proceed with the remaining trial visits and procedures unless they withdraw their consent. The frequency of use of emergency medications is recorded as a concomitant medication during the follow-up period from screening to EOT / ET and is confirmed by the clinic staff. Subjects who require further treatment with prohibited drugs discontinue the trial treatment and can undergo the follow-up trial procedures.

[0158] Participants should complete the ANMS GCSI-DD daily to describe the worst severity of each symptom over the past 24 hours. Therefore, the ANMS GCSI-DD questionnaire score should reflect the worst severity of each symptom.

[0159] (e) Overall restrictions and dietary restrictions Participants should maintain their normal diet and lifestyle consistently throughout the study.

[0160] For all participants, the use of grapefruit, grapefruit products, starfruit products, and Seville oranges is prohibited from 48 hours before randomization until the end of treatment (EOT).

[0161] Participants are required to fast for 2 hours and 1 hour before the entire administration.

[0162] Participants are required to fast for at least 8 hours before the scheduled GEBT and for 4 hours after the GEBT meal is completed.

[0163] The PK subset providing post-administration PK samples at the 5th, 6th, and / or 7th visits is required to fast for at least 8 hours before morning administration of the study drug and for at least 3 hours after administration of the study drug.

[0164] E. Evaluation of effectiveness (i) Effectiveness endpoints (a) Primary efficacy endpoint The primary efficacy endpoint of this study is to evaluate the effect of dudomperidone on significantly reducing gastroparesis-related symptoms compared to baseline in adult patients with diabetic gastroparesis, compared to placebo, based on a composite score of the mean ANMS GCSI-DD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period.

[0165] (b) Secondary efficacy endpoints The secondary efficacy endpoints of this study include the following evaluation of the effect of dudomperidone compared to placebo in adults with diabetic gastroparesis: ● Percentage of patients identified as responders, defined as a mean decrease of ≥0.5 from baseline in the combined score of the ANMS GCSIDD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period. ● Percentage of patients who achieved a 30% or greater reduction from baseline in the mean composite score of ANMS GCSI-DD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period. ● The combined score of the ANMS GCSI-DD total score, nausea subscale score, and vomiting score, as well as the percentage of symptom-free days in the subscale scores, over the last two weeks of the 12-week treatment period (symptom days are defined as scores assessed as >mild [ANMS GCSI-DD score ≥ 2]). ● Estimation based on a composite score of mean ANMS GCSI-DD nausea subscale score and vomiting score, using PGIS and PGIC as anchors over a 12-week treatment period. ● Percentage of subjects with a history of lack of response, showing a 30% or greater reduction from baseline, based on the mean composite score of ANMS GCSIDD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period, or who were unable to tolerate metoclopramide therapy or other exercise stimulants such as erythromycin, neostigmine, or bethanechol. ● The effect of dudonperidone on significantly reducing gastroparesis-related symptoms compared to baseline, based on mean ANMS GCSI-DD total score and subscale scores over the last two weeks of a 12-week treatment period. ● Change in the mean composite score of ANMS GCSI-DD nausea subscale score and vomiting score from baseline over the last two weeks of a 12-week treatment period in subjects receiving GLP-1RA. ● Percentage of respondents taking GLP-1RAs who showed a mean reduction of 0.5 or more from baseline in the ANMS GCSI-DD nausea subscale score and vomiting score over the last two weeks of the 12-week treatment period. ● Percentage of patients taking GLP-1RAs who achieved a 30% or greater reduction in their ANMS GCSI-DD nausea subscale score and vomiting score from baseline during the last two weeks of a 12-week treatment period. ● Changes in ANMS GSCI-DD total score and composite symptoms related to gastroparesis from baseline to the last two weeks of the 12-week treatment period in subjects receiving GLP-1RA. ● All of the above primary and secondary endpoints evaluated during the last two weeks of the 12-week treatment period will also be evaluated during the last six weeks of the 12-week treatment period. ● Changes from baseline to week 12 using PGIS. ● Changes from baseline to week 12 in PGIC.

[0166] (c) Exploratory efficacy endpoints The exploratory efficacy endpoint of this study includes evaluation of dudonperidone compared to placebo in adults with diabetic gastroparesis for the following: ● Percentage of subjects identified as responders defined as having a mean decrease of 0.5 or greater from baseline in both the mean ANMS GCSI-DD total score and subscale scores over the last two weeks of the 12-week treatment period and the last six weeks of the 12-week treatment period. ● Percentage of patients who achieved a mean reduction of 30% or more in their ANMS GCSI-DD total score and subscale scores from baseline during the last two weeks of the 12-week treatment period, and during the last six weeks of the 12-week treatment period. ● Estimates based on mean ANMS GCSI-DD total score and subscale score using PGIS and PGIC as anchors over a 12-week treatment period. ● The effect of dudonperidone on significantly reducing gastroparesis-related symptoms compared to baseline, based on mean ANMS GCSI-DD vomiting subscale scores over the last two weeks of the 12-week treatment period and the last six weeks of the 12-week treatment period. ● Change from baseline compared to placebo after 12 weeks of treatment in PAGI-QoL. ● Change from baseline compared to placebo after 12 weeks of treatment in the GERDQ. ● Changes in HbA1c, insulin requirements, and diabetes medication use from baseline to week 12. ● Changes in gastric emptying from baseline to week 12, as measured by GEBT. ● Effect on the percentage of days and number of days of use of any emergency medication compared to placebo over a 12-week treatment period. ● Primary and secondary endpoints related to the evaluation of the ANMS GCSI-DD vomiting score will be used for exploratory analysis of vomiting severity. ● Characterization of the absorption of dudomperidone and the concentration of its primary metabolites under stable conditions. ● Characterization of the exposure-response relationship of dudonperidone, as well as various measurements of efficacy and / or safety, may also be performed.

[0167] (ii)ANMS GCSI-DD questionnaire The ANMS GCSI-DD questionnaire targets five major gastroparesis-related symptoms: nausea, early satiety, postprandial bloating, epigastric pain, and vomiting. Bloating is included as an exploratory symptom. Symptoms are assessed using a numerical severity scale from 0 (none) to 4 (very severe). Vomiting is captured using a frequency scale and scored as follows: 0 for no episodes, 1 for one episode, 2 for two episodes, 3 for three episodes, and 4 for four or more episodes.

[0168] Participants will be instructed to complete the ANMS GCSI-DD questionnaire daily from screening, during the ANMS GCSI-DD baseline period, on the day of randomization, and daily from day 1 to day 84 (±4 days). Materials will be distributed at the screening visit. Adherence to the ANMS GCSI-DD will be assessed at the time of randomization (day 1), and a rate of 75% or higher is required to be eligible for the trial.

[0169] Participants are instructed to complete a questionnaire by assessing their severity and vomiting episode response over the past 24 hours, providing the number of vomiting episodes, with the worst-case severity being the most severe symptom.

[0170] The daily ANMS GCSI-DD total symptom score is calculated by adding up the scores for each of the five symptom items and then dividing by 5. Therefore, the maximum total symptom score can be 4 (5 symptoms × maximum score 4 = 20, 20 ÷ 5 = 4).

[0171] Baseline for the analysis of ANMS GCSI-DD total scores and subscale scores is based on the mean of daily measurements over 14 days prior to randomization. Both ANMS GCSI-DD total scores and subscale scores are analyzed to compare symptom scores between treatment groups. At least four days of valid non-missing responses are required over a 7-day period to obtain the mean weekly score for a given subscale score.

[0172] Record the ANMS GCSI-DD questionnaire.

[0173] (iii) PGIS and PGIC PGIS evaluation will begin at the first visit and be performed once a week. At the third visit, PGIS will be performed before the first dose of the investigational drug, and this will be used as the baseline.

[0174] The Post-Grade Symptom Severity Index (PGIS) is a single-item scale completed by the patient at the time of their visit to assess their current overall severity over the past seven days. The PGIS is evaluated using a 5-point numerical rating scale. The PGIS score should be recorded.

[0175] PGIC evaluation will be performed during the 4th, 5th, 6th, and 7th visits.

[0176] The PGIC is a single-item scale, completed at each visit, used to assess changes in gastroparesis symptoms after initiating the investigational drug. The PGIC is evaluated using a 5-point numerical scale. Record the PGIC score.

[0177] (iv) PAGI-QoL equipment survey PAGI-QoL will be completed at the clinic during the first, third, fourth, fifth, sixth, and seventh visits prior to the initial administration of the investigational drug.

[0178] The PAQI-QoL consists of 30 questions that ask about the impact of some of the gastrointestinal problems the subject may be experiencing on their overall quality of life and well-being.

[0179] (v) Gastroesophageal reflux disease questionnaire The GERDQ should be completed at the clinic during the first, third, fourth, fifth, sixth, and seventh visits prior to the first administration of the investigational drug.

[0180] The GERDQ is an assessment of the subject's symptoms from the previous week. The GERDQ score is the sum of the scores for the individual questions, ranging from 0 to 18.

[0181] (vi) Gastric emptying breath test Baseline measurement of gastric emptying using stable isotope GEBT is completed at the clinic. While baseline GEBT is preferably performed during the induction period (second visit, -21 to -12 days), it may be performed outside the -21 to -12 day window, as long as the trial is conducted on a day prior to the expected randomization date that will allow sufficient time for GEBT analysis. If, at the first visit, the subject arrives at the clinic, is not taking any exclusion medications, and meets all required criteria specified in the protocol (e.g., minimum 8 hours of fasting, <275 mg / dL glucose level, etc.), the procedures for the first and second visits may be performed on the same day.

[0182] If a subject is rescreened after a screening failure for reasons other than the GEBT results, a repeat GEBT is not necessary if the test was completed within the past three months prior to the rescreening and the results meet the eligibility criteria.

[0183] Regarding the selection criteria, GEBT will also be performed at the 7th visit (EOT) or ET.

[0184] Participants who actively use nicotine-containing products must refrain from using these products from the time they wake up on the morning of the GEBT until the completion of the test. Participants must agree to refrain from using opioids for ≥72 hours or 5 half-lives (whichever is greater) prior to the GEBT. Participants who follow a stable non-routine use regimen must agree to refrain from prescribed marijuana and / or THC-containing products for at least 24 hours prior to the GEBT. Participants are not required to discontinue GLP-1RAs before the GEBT and should maintain their prescribed dose.

[0185] GEBT involves taking two pre-meal breath samples, consuming a GEBT meal, and taking post-meal breath samples at six time points (45, 90, 120, 150, 180, and 240 minutes). The GEBT meal should be consumed within 10 minutes.

[0186] Eligibility is determined by the percentage (abbreviated as PCD) of the amount excreted at time t after ingesting the test food.

[0187] TIFF2026511098000014.tif22129In formula, DOB = the ratio between the postprandial breath sample and the baseline breath sample at any given time (t minutes) [ 13 CO2 / 12 [CO2] measurement difference. CO2PR = CO2 production rate (mmol CO2 / min) calculated using the Schofield formula (26) which incorporates the subject's age, sex, height, and weight. R s =Ratios in the reference standard material (Pee Dee belemnite) for these measurements [ 13 CO2 / 12 CO2, R s =0.0112372 13 = Atomic weight of carbon-13 10 = a constant coefficient for unit conversion Dosage = administered to subjects in the test diet [ 13 [C]-Weight of carbon-13 in the amount of Spirulina platensis (mg). 13 [C]-S. platensis has approximately 43% carbon-13, therefore a dose of 100 mg [ 13 [C]-S. platensis corresponds to approximately 43 mg of carbon-13.

[0188] A subject is diagnosed with delayed gastric emptying if their kPCD value at 90 minutes, 120 minutes, or 150 minutes falls below the respective cutoff point, and / or if their maximum kPCD value occurs at 240 minutes.

[0189] The delay cutoff parameters for each time point are shown in Table 6 below.

[0190] (Table 6) Cutoff points of GEBT kPCD delay TIFF2026511098000015.tif21128

[0191] To confirm the presence of delayed gastric emptying based on established diagnostic criteria, all subjects will complete a baseline GEBT at their second visit, as described above. For selected subjects, the GEBT will be performed at the seventh visit (EOT) or at ET.

[0192] (vii) Pharmacokinetic evaluation PK samples are collected according to the procedure schedule in Table 7.

[0193] The plasma concentrations of dudomperidone and its primary metabolites are measured and used to estimate the following parameters. ● Stable state C based on samples taken after administration at the 5th visit in the initial PK subset. max . ● Steady-state trough concentration based on samples taken before medication administration at the 5th and 7th visits.

[0194] (viii) Pharmacological genomics evaluation For patients who have submitted written informed consent to participate in the optional PGx evaluation, blood samples will be collected at any point during the treatment period.

[0195] PGx samples may be used in genetic studies to explore the underlying causes of variability and / or differences in responses in PK, PD, and / or safety data after administration of dudomperidone. Participants will be given the option to participate in PGx evaluation during the study's consent process. Participants may withdraw their consent to participate in PGx evaluation at any point during the study without withdrawing their consent to participate in the study.

[0196] F. Safety Evaluation The safety of dudonperidone will be evaluated from the time of informed consent to the end of the follow-up period. All safety endpoints will be summarized descriptively. Safety endpoints include: ● Incidence of clinically significant changes in laboratory parameters, physical examination findings, 12-lead ECG parameters, body weight, and vital signs. ● TEAE. ● SAEs that occur under treatment. ● TEAE can lead to early discontinuation of the test drug. ● Significant laboratory abnormalities occurring under treatment.

[0197] (Table 7A) Procedure Schedule TIFF2026511098000016.tif166170

[0198] (Table 7B) TIFF2026511098000017.tif245170TIFF2026511098000018.tif248170TIFF2026511098000019.tif248170TIFF2026511098000020.tif77170

Claims

1. A method for treating a person diagnosed with diabetic gastroparesis, comprising administering a dosage form containing 10 mg or 15 mg of dudonperidone as a BID, wherein the administration reduces the severity of the gastroparesis-related symptoms in the person compared to baseline.

2. The method according to claim 1, wherein the dosage form is a capsule.

3. The method according to claim 2, wherein the capsule further comprises one or more of (i) a medium-chain triglyceride, (ii) glyceryl distearate, (iii) butylated hydroxyanisole, and (iv) butylated hydroxytoluene.

4. The method according to claim 2 or 3, wherein the capsule further comprises one or more of (i) 85.1 mg of medium-chain triglycerides, (ii) 9.75 mg of glyceryl distearate, (iii) 0.1 mg of butylated hydroxyanisole, and (iv) 0.05 mg of butylated hydroxytoluene.

5. The method according to claim 2 or 3, wherein the capsule further comprises one or more of (i) 80.1 mg of medium-chain triglycerides, (ii) 9.75 mg of glyceryl distearate, (iii) 0.1 mg of butylated hydroxyanisole, and (iv) 0.05 mg of butylated hydroxytoluene.

6. The method according to any one of claims 1 to 3 and 5, wherein the dosage form is a single capsule containing 10 mg of dudonperidone.

7. The method according to any one of claims 1 to 4, wherein the dosage form comprises a single capsule containing 5 mg of dudonperidone and a single capsule containing 10 mg of dudonperidone.

8. The method according to any one of claims 1 to 7, wherein the patient has an average weekly nausea subscale score of 2 or more prior to the administration of dudonperidone.

9. The method according to any one of claims 1 to 8, wherein the patient has had at least one average weekly vomiting episode prior to the administration of dudonperidone.

10. The method according to any one of claims 1 to 9, wherein the reduction in severity is based on a composite score of the mean human ANMS GCSI-DD nausea subscale score and vomiting subscale score.

11. The method according to claim 11, wherein the gastroparesis-related symptoms are one or more of the following: postprandial nausea, postprandial vomiting, postprandial bloating, early satiety, abdominal distension, upper abdominal pain, or abdominal pain.

12. The method according to any one of claims 1 to 11, wherein the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 0.5 points compared to baseline.

13. The method according to any one of claims 1 to 12, wherein the human ANMS GCSI-DD nausea subscale score and vomiting score are reduced by at least 30% compared to baseline.

14. The method according to any one of claims 1 to 13, wherein the percentage of days free of gastroparesis-related symptoms in the person increases compared to baseline.

15. The method according to any one of claims 1 to 14, wherein the PAGI-QoL score of the person is improved compared to baseline.

16. The method according to any one of claims 1 to 15, wherein the GERDQ score of the person is improved compared to a baseline.

17. The method according to any one of claims 1 to 16, wherein the PGIS score of the person is improved compared to a baseline.

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