Methods for treating diabetic gastroparesis

Abstract

The disclosure provides methods for treating diabetic gastroparesis.

Description

METHODS FOR TREATING DIABETIC GASTROPARESISCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of the priority of U.S. Provisional Patent Application No. 63 / 491,823, filed March 23, 2023, the contents of which are incorporated by reference herein.TECHNICAL FIELD

[0002] The disclosure provides methods for treating diabetic gastroparesis.BACKGROUND

[0003] Gastroparesis is defined as impaired gastric emptying in the absence of physical gastric outlet obstruction. Symptoms include early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. The disease is often associated with diabetes or may occur after gastric surgery: it may also be idiopathic. Gastroparesis affects the patient’s nutritional state, especially in diabetics, and severe symptoms of gastroparesis can lead to other complications such as malnutrition, esophagitis, and Mallory-Weiss tears. Gastroparesis negatively impacts a patient's quality of life, causing decreased social interaction, poor work functionality, and development of anxiety or depression.

[0004] The first-line treatment for gastroparesis involves nutritional management and support, including fluid and electrolyte replacement. Pharmacologic therapy is directed at increasing gastric emptying and accelerating intestinal transit time. Currently, metoclopramide, a dopamine D2 receptor antagonist, is the only United States Food and Drug Administration (FDA)-approved agent for the treatment of gastroparesis. While effective, this agent readily crosses the blood-brain barrier resulting in central nervous system (CNS) side effects in up to 40% of patients. Common CNS effects associated with metoclopramide treatment include restlessness, drowsiness, fatigue, and lassitude; however, the major safety concern with metoclopramide treatment is the development of tardive dyskinesia. Tardive dyskinesia is a disorder characterized by involuntary movements of the face, tongue, or extremities and is often irreversible. Increased risk of developing tardive dyskinesia correlates to treatment duration; therefore, it is recommended that therapy with metoclopramide not exceed 12 weeks.

[0005] New methods for treating diabetic gastroparesis are needed.SUMMARY OF THE INVENTION

[0006] In some embodiments, the disclosure provides methods of treating a human diagnosed with diabetic gastroparesis comprising administering a dosage form comprising 10 mg or 15 mg of deudomperidone BID, wherein the administration decreases the severity of the human’s gastroparesis-related symptoms, as compared to baseline.DESCRIPTION OF THE DRAWINGS

[0007] Fig. 1 is the study scheme for Example 3. PK Subset Analysis: After approximately 30 subjects in PK Subset A complete Visit 5, emerging PK and safety data will be evaluated. Interim Analysis: During the study, 1 unblinded IA will be performed once approximately 50% of the randomized subjects complete the EOT Visit or have discontinued early.DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0008] In the disclosure, the singular forms “a,” “an,” and “the” include the plural reference, and reference to a particular numerical value includes at least that particular value, unless the context clearly indicates otherwise. Thus, for example, a reference to “a material” is a reference to at least one of such materials and equivalents thereof know n to those skilled in the art, and so forth.

[0009] When a value is expressed as an approximation by use of the descriptor “about” it will be understood that the particular value forms another embodiment. In general, use of the term “about” indicates approximations that can vary depending on the desired properties sought to be obtained by the disclosed subject matter and is to be interpreted in the specific context in which it is used, based on its function. The person skilled in the art will be able to interpret this as a matter of routine. In some cases, the number of significant figures used for a particular value may be one non-limiting method of determining the extent of the word “about.” In other cases, the gradations used in a series of values may be used to determine the intended range available to the term “about” for each value. Where present, all ranges are inclusive and combinable. That is. references to values stated in ranges include every value within that range.

[0010] When a list is presented, unless stated otherwise, it is to be understood that each individual element of that list and every' combination of that list is to be interpreted as a separate embodiment. For example, a list of embodiments presented as “A, B, or C” is to beinterpreted as including the 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 mammals. In some embodiments, the patient or subject is a human. In other embodiments, the patient or subject is a veterinary or farm animal, a domestic animal or pet, or animal used for conducting clinical research.

[0012] “Treating” or variations thereof refers to eliminating or reducing at least one physical parameter of the disease or disorder.

[0013] “Deudomperidone” and “d4-domperidone” as referenced herein are interchangeable and refer to !-{3-[4-(5-chloro-2-oxo-2,3-dihydro-lH-l,3-benzodiazol-l- yl)piperidin-lyl]propyl}-2,3-dihydro(4,5,6,7-D4)-lH-l,3-benzodiazol-2-one, which has the following structure:

[0014] Any reference to deudomperidone may also include, where noted, pharmaceutically acceptable salts, esters, hydrates, solvates, prodrug forms, and derivatives of these, which are broadly defined as deudomperidone compounds that are modified or partially substituted, examples include but are not limited to adding a single atom, adding a reactive group, adding a functional group, forming a dimer or multimer, conjugating to another molecule such as an antibody, etc.

[0015] “Pharmaceutically acceptable” refers to properties and / or substances that are acceptable to the patient from a pharmacological / toxicological vantage, and to the manufacturing pharmaceutical chemist from a physical / chemical vantage regarding composition, formulation, stabi litx . patient acceptance, and bioavailability.

[0016] A pharmaceutically acceptable salt includes salts with a pharmaceutically acceptable acid or base, e.g., inorganic acids, e.g, hydrochloric, sulfuric, phosphoric, diphosphoric, hydrobromic, hydroiodic and nitric acid and organic acids, for example citric, fumaric, maleic, malic, mandelic, ascorbic, oxalic, succinic, tartaric, benzoic, acetic, methanesulphonic, ethanesulphonic, benzenesulphonic, cyclohexylsulfamic (cyclamic) or p- toluenesulphonic acid. Pharmaceutically acceptable bases include alkali metal, e.g. sodiumor potassium, and alkali earth metal, e.g. calcium or magnesium, hy droxides, and organic bases, e.g., alkyl amines, arylalkyl amines and heterocyclic amines.

[0017] The abbreviation “D,” as used herein, refers to a stable isotope of hydrogen that is deuterium (heavy hydrogen or2H). Such instances of “D” include an amount of deuterium that is above the naturally occurring distribution of deuterium. In some embodiments, D has deuterium enrichment of no less than about 1%. In other embodiments,D has a deuterium enrichment of no less than about 5%. In further embodiments, D has a deuterium enrichment of no less than about 10%. In still other embodiments, D has a deuterium enrichment of no less than about 20%. In still other embodiments, D has a deuterium enrichment of no less than about 30%. In still other embodiments, D has a deuterium enrichment of no less than about 40%. In yet further embodiments, D has a deuterium enrichment of no less than about 50%. In still other embodiments, D has a deuterium enrichment of no less than about 60%. In other embodiments, D has a deuterium enrichment of no less than about 70%. In further embodiments, D has a deuterium enrichment of no less than about 80%. In yet other embodiments, D has a deuterium enrichment of no less than about 90%. In still further embodiments, D has a deuterium enrichment of no less than about 98% of deuterium. In still further embodiments, D has a deuterium enrichment of no less than about 99% of deuterium. In still further embodiments, D has a deuterium enrichment of at least 99% of deuterium.

[0018] As used herein, “baseline"’ refers to a human’s score, or average of scores, on a particular measure, prior to any administration of deudomperidone, as described herein. Baseline can be established, e.g., just prior to deudomperidone administration or up to about 7 days or up to about 14 days prior to deudomperidone administration. For example, baseline can be established about 30 minutes prior to the first administration of deudomperidone. In other aspects, baseline can be established 1 day prior to the first administration of deudomperidone. In other aspects, baseline can be established 2 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 3 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 4 days prior to the first administration of deudompendone. In other aspects, baseline can be established 5 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 6 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 7 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 8 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 9 days priorto the first administration of deudomperidone. In other aspects, baseline can be established 10 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 1 1 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 12 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 13 days prior to the first administration of deudomperidone. In other aspects, baseline can be established 14 days prior to the first administration of deudomperidone.

[0019] The disclosure provides methods of treating a human diagnosed with diabetic gastroparesis. The term “diabetic gastroparesis” as used herein refers to human having diabetes and gastroparesis. In some embodiments, the human has Type 1 diabetes. In other embodiments, the human has Type 2 diabetes. The term "gastroparesis" as used herein refers to a disorder involving delayed gastric emptying in the absence of physical gastric outlet obstruction.

[0020] The methods comprise administering a dosage form comprising 10 mg or 15 mg of deudomperidone BID to the human. In some embodiments, 20 mg of deudomperidone is administered to the human. In other embodiments. 30 mg of deudomperidone is administered to the human. For example, the free base of deudomperidone is administered to the human.

[0021] Deudomperidone may be administered as needed to attain the desired daily dosage. For example, the deudomperidone can be administered in divided doses. In some embodiments, the deudomperidone is two times daily (BID). In further embodiments, a 20 mg dose of deudomperidone is administered 10 mg BID. In other embodiments, a 30 mg dose of deudomperidone is administered 15 mg BID. In still further embodiments, a 20 mg dose of deudomperidone is administered 20 mg BID, given as a single 10 mg capsule of deudomperidone BID. In yet other embodiments, a 30 mg dose of deudomperidone is administered 15 mg BID, given as a single 10 mg capsule and a single 5 mg capsule.

[0022] Deudomperidone may be formulated for administration in a dosage form, e.g, solid form. In some embodiments, the pharmaceutical formulations are formulated in the form of a tablet, caplet, capsule, powder, or softgel, or a combination thereof. In other embodiments, the pharmaceutical formulations are formulated in the form of a tablet. In further embodiments, the pharmaceutical formulations are formulated in the form of a caplet. In yet other embodiments, the pharmaceutical formulations are formulated in the form of a capsule. In still further embodiments, the pharmaceutical formulations are formulated in the form of a powder. In other embodiments, the pharmaceutical formulations are formulated inthe form of a softgel. In further embodiments, the dosage form is a single capsule comprising 10 mg of deudomperidone. In yet other embodiments, the dosage form a single capsule comprising 5 mg of deudomperidone and a single capsule comprising 10 mg of deudomperidone.

[0023] The dosage form, e.g., capsule, comprises one or more of (i) medium chain triglycerides, (ii) glyceryl distearate, (iii) butylated hydroxyanisole, and (iv) butylated hydroxytoluene. In some embodiments, the dosage form contains a glyceryl distearate. The term ’‘glyceryl distearate” as used herein refers to a compound having glyceryl and two stearate components as shown below, where the components are bound together to form a chemically stable molecule.glyceryl stearateIn certain aspects, the glyceryl distearate is a glyceryl 1,3-distearate. In further aspects, the capsule contains 9.75 mg of glycery l distearate.

[0024] In other embodiments, the dosage form, e.g., capsule, contains a medium chain triglyceride. The term “medium chain triglyceride” as used herein refers to triglycerides where the fatty acid moiety have an aliphatic tail of about 6 to about 12 carbon atoms. In some aspects, the fatty' acid moiety7has an aliphatic tail of 6, 7, 8, 9, 10, 11, or 12 carbon atoms. In further aspects, the fatty acid aliphatic tails are the same. In other aspects, the fatty acid aliphatic tails are different. In still further aspects, the fatty acid has an aliphatic tail of 6 carbon atoms, z.e., the medium chain triglyceride is caproic acid. In yet other aspects, the fatty acid has an aliphatic tail of about 8 carbon atoms, i.e., the medium chain triglyceride is capry lic acid. In other aspects, the fatty7acid has an aliphatic tail of about 10 carbon atoms, i.e., the medium chain triglyceride is capric acid. In further aspects, the fatty acid has an aliphatic tail of about 12 carbon atoms, i.e., the medium chain triglyceride is lauric acid. In yet other aspects, the capsule contains 85. 1 mg of medium chain triglycerides. In still further aspects, the capsule contains 80.1 mg of medium chain triglycerides.

[0025] In further embodiments, the dosage form, e.g., capsule, contains one or more antioxidants. In some aspects, the dosage form contains butylated hydroxyanisole (BHA). butylated hydroxytoluene (BHT), or a combination thereof. In other aspects, the antioxidant is BHA. In further embodiments, the antioxidant is BHT. In further aspects, the antioxidant is BHA and BHT. In further aspects, the capsule contains 0.05 mg of butylated hydroxytoluene. In other aspects, the capsule contains 0. 10 mg of butylated hydroxy anisole.In yet further aspects, 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 hydroxy anisole, and (iv) 0.05 mg of butylated hydroxy toluene. In other 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 hydroxy anisole, and (iv) 0.05 mg of butylated hydroxytoluene. In yet other embodiments, 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] Prior to administering deudomperidone, the patient has an ANMS GCSI-DD average weekly nausea sub-scale score of 2 or greater. In some embodiments, the patient has an ANMS GCSI-DD average weekly nausea sub-scale score of 2. 3, or 4. In other embodiments, the patient has an ANMS GCSI-DD nausea subscale score of 2 or greater for at least about 14 days, prior to administering deudomperidone.

[0028] Prior to administering deudomperidone, the patient has a weekly average of at least one vomiting episode. The term “vomiting / ’ as used herein, refers to the oral eviction of gastrointestinal contents, due to contractions of the gut and muscles of the thoracoabdominal wall. In some embodiments, the patient has a weekly average of at least one vomiting episode of any severity. In other embodiments, the patient has a weeklyaverage of at least 1, 2, 3, 4, or 5 vomiting episodes, prior to administering deudomperidone.

[0029] One of skill in the art would be able to calculate / determine ANMS GCSI- DD scores. See, e.g., “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 on symptom items (e.g., nausea, early satiety, postprandial fullness, upper abdominal pain, and number of vomiting episodes) and then dividing by 5, that is the number of items within the gastroparesis related symptom score. Thus, the maximum total symptom score could be (5 symptoms * maximum score 4 divided by 5); hence, the maximum score is 20 / 5=4. High scores on the ANMS GCSI-DD reflect greater symptom severity. See, e.g., “User Manuel for the ANMS GCSI-DD,” FederalDrug Administration at https: / / www.fda.gov / media / 125038 / download, which is hereby incorporated by reference.

[0030] Desirably, the administration decreases the severity of the human’s gastroparesis-related symptoms, as compared to baseline. Gastroparesis-related symptoms include one or more of postprandial nausea, postprandial vomiting, postprandial fullness, early satiety, bloating, 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 fullness. In still other embodiments, the gastroparesis-related symptom is early satiety. In yet further embodiments, the gastroparesis- related symptom is bloating. In other embodiments, the gastroparesis-related symptom is epigastric pain. In further embodiments, the gastroparesis-related symptom is abdominal pain.

[0031] The decrease in severity' is based on a composite of the human’s average ANMS GCSI-DD nausea sub-scale and vomiting sub-scale scores. One of skill in the art would be able to calculate such sub-scale using the techniques described herein. In some embodiments, the human’s ANMS GCSI-DD nausea sub-scale and vomiting scores reduce by at least 0.5 points, as compared to baseline. In other embodiments, the human’s ANMS GCSI-DD nausea sub-scale and vomiting scores reduce by at least 0.5, 1, 1.5, 2, 2.5, 3. 3.5 or 4 points, as compared to baseline. In further embodiments, the human’s ANMS GCSI-DD nausea sub-scale and vomiting scores reduce by at least 0.5 to 4, 0.5 to 3.5, 0.5 to 3, 0.5 to 2.5, 0.5 to 2, 0.5 to 1.5, 0.5 to 1, 1 to 4, 1 to 3.5, 1 to 3, 1 to 2.5, 1 to 2, 1 to 1.5, 1.5 to 4, 1.5 to 3.5, 1.5 to 3, 1.5 to 2.5, 1.5 to 2. 2 to 4, 2 to 3.5, 2 to 3, 2 to 2.5, 2.5 to 4, 2.5 to 3.5, 2.5 to 3, 3 to 4, 3 to 3.5, or 3.5 or 4 points, as compared to baseline.

[0032] In other embodiments, the human’s ANMS GCSI-DD nausea sub-scale and vomiting scores reduce by at least 30%, as compared to baseline. In yet further embodiments, the human’s ANMS GCSI-DD nausea sub-scale and vomiting scores reduce by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, as compared to baseline. In still other embodiments, the human’s ANMS GCSI-DD nausea sub-scale and vomiting scores reduce by 30 to 100%, 30 to 90%, 30 to 80%, 30 to 70%, 30 to 60%, 30 to 50%, 30 to 40%, 40 to 100%, 40 to 90%, 40 to 80%, 40 to 70%, 40 to 60%, 40 to 50%, 50 to 100%, 50 to 90%, 50 to 80%, 50 to 70%, 50 to 60%, 60 to 100%, 60 to 90%, 60 to 80%, 60 to 70%, 70 to 100%, 70 to 90%, 70 to 80%, 80 to 100%. 80 to 90%. or 90 to 100%. as compared to baseline.

[0033] After administration of deudomperidone. in some embodiments, the human’s percentage of gastroparesis-related symptom-free days increases, as compared to baseline. In other embodiments, the human’s PAGI-QoL score improves, as compared to baseline. In further embodiments, the human’s GERDQ score improves, as compared to baseline. In yet other embodiments, the human’s PGIS score improves, as compared to baseline.

[0034] Aspects

[0035] Aspect 1 : A method of treating a human diagnosed with diabetic gastroparesis comprising administering 10 mg or 15 mg of deudomperidone BID, wherein the administration decreases the severity of the human’s gastroparesis-related symptoms.

[0036] Aspect 2: The method of aspect 1, wherein the decrease in severity is based on a composite of the human’s average ANMS GCSI-DD Nausea Sub Scale and Vomiting Sub-Scale Scores.

[0037] Aspect 3: A method as described substantially herein.

[0038] Example 1

[0039] A. Study Description

[0040] (i) Summary' of Study Design

[0041] This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of deudomperidone in adult subjects with diabetic gastroparesis after 12 weeks of treatment.

[0042] The safety of deudomperidone will be assessed from the time of informed consent until the end of the Follow-Up Period. Subjects will be followed for efficacy and adherence to study drug throughout the Double-Blind Treatment Period. Plasmaconcentrations of deudomperidone will also be measured at select visits during the DoubleBlind Treatment Period.

[0043] The total duration of study participation will be approximately 18 weeks including a Screening Period and Lead-In Period of <5 weeks, a Double-Blind Treatment Period of 12 weeks, and a Follow-Up Period of up to 1 week. Over the course of their participation, subjects will complete 8 visits (subjects with documented delayed gastric emptying within 2 years of Visit 1 may complete Visit 2 via a phone call).

[0044] Subjects who complete the Screening and Lead-In Periods and remain eligible will be randomized in parallel to 1 of 3 treatment groups in a 1 : 1 : 1 fashion for 12 weeks:• Deudomperidone 15 mg BID, administered as a single 10-mg capsule and a single 5-mg capsule;• Deudomperidone 10 mg BID, administered as a single 10-mg capsule of deudomperidone and a single placebo capsule; or• Placebo for deudomperidone BID, administered as 2 matching placebo capsules.

[0045] Approximately 400 subjects (133 subjects per treatment group) will be randomized with 363 subjects anticipated to complete the 12-week Double-Blind Treatment Period. Subjects will be stratified according to their gender at birth (female, male) and by the baseline composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting SubScale Scores (<2.6 versus >2.6).

[0046] Pharmacokinetics

[0047] All subjects participating in the study will have trough PK samples collected at Visits 5 and 7 within 60 minutes prior to study drug administration.

[0048] Subjects may opt to participate in a PK sub-set in which post-dose PK sample(s) will also be collected at Visit 5. These subjects will remain in the clinic for up to approximately 3 hours after the morning dose of study drug. In addition to the blood sample collected for PK within 60 minutes prior to study drug administration, blood samples will be collected from subjects in the PK sub-set at approximately 1 and 2 hours post-dose. If the subject is willing and able to remain in the clinic longer, a PK sample will also be collected at approximately 3 hours post-dose. Additional samples may be collected within the following post-dose windows on that same day if the subject is willing to return to the site: 4 to 8 hours and / or 8 to 12 hours. Subjects will be instructed to record the date and time of each dose onthe 2 days prior to Visit 5 and also will be instructed not to take the study drug at home the day of Visit 5. Post-dose PK samples will be collected within ±15 minutes of the nominal time.

[0049] After approximately 30 subjects in the PK sub-set complete Visit 5, an iDMC will evaluate emerging PK and safety data while blinded to individual subject assignment to determine the dose level(s) to be carried forward for the remainder of the study.

[0050] Once the initial data review is complete, post-dose samples will be collected at Visit 5, 6, and / or 7 within the following post-dose windows: 1 to 4 hours, 4 to 8 hours, or 8 to 12 hours in, at minimum, a sub-set of subjects. For subjects who opt to provide more than 1 sample, efforts will be made to collect each sample within a different window. Subjects will be instructed to record the date and time of each dose on the 2 days prior to the visit and also will be instructed not to take the study drug at home the day of the visit.

[0051] In the event of an SAE or AE leading to withdrawal, an effort will be made to collect a PK sample as soon as possible.

[0052] Interim analysis

[0053] During the study, 1 interim analysis (IA) will be performed once approximately 70% of the randomized subjects complete the EOT Visit or have discontinued early. The iDMC will convene, evaluating for safety’, early futility, and potential sample size recalculation. The IA of the primary endpoint will be for early futility’ or sample size increase only. The study will not be stopped for overwhelming efficacy.

[0054] General study design and procedures

[0055] Subjects must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for study participation. Subjects will be evaluated as follows:• Screening Period (Visit 1, Days -35 to -22): o Screening procedures will be performed and subjects will begin washout of any applicable excluded medications. Subjects will be required to washout of any prohibited medications for at least 14 days or 5 half-lives (whichever is longer) prior to beginning the ANMS GCSI-DD Baseline Period (defined as the 7 or 14 days prior to randomization, depending on if the subject meets Randomization Criterion 4a or 4b) and / or performing the GEBT at Visit 2; ando Beginning in the evening of the Screening Visit, the subject will record the ANMS GCSI-DD, PAGI-QoL, GERDQ, PGIS. and the use of allowable rescue medication, according to the Tables 1A and IB.• Lead-In Period (Visit 2, Days -21 to -1): o For subjects with documented delayed gastric emptying within 2 years of Visit 1, this visit may be completed via a telephone call to the subject to assess adherence to the subject diaries, concomitant medications, and AEs. If the subject would require additional evaluation requiring a visit to the clinic, the subject may report to the clinic for additional procedures falling under Unscheduled Visits. o The subject will be asked to continue completion of the ANMS GCSI-DD questionnaire daily and recording the use of allowable rescue medication daily; o The average of the ANMS GCSI-DD daily measurements obtained from the period of 7 or 14 days prior to randomization will constitute '’baseline" measurements; and o GEBT : For subj ects who do not have documented delayed gastric emptying within 2 years of Visit 1, a GEBT will be performed on a single day between Days -21 to -12, inclusive. The GEBT will be performed after a minimum 14-day or 5 half-lives (whichever is longer) washout from the agents discussed below. Subjects will fast for a minimum of 8 hours before the GEBT. The GEBT will have breath samples obtained twice prior to consumption of a standardized,13C-enriched meal and then at 45, 90, 120, 150, 180, and 240 minutes after meal consumption. Fasting glucose will be assessed before GEBT to ensure a blood glucose level of <275 mg / dL. If the subject's fasting blood glucose level is >275 mg / dL, the GEBT will not be performed. The subject will be allowed to return to the site within the next 1 to 3 days to complete the test, or the subject may be excluded from the study, if the subject no longer meets the criteria for stable, well-controlled blood glucose. On the day of the GEBT, subjects will present at the clinic after an overnight fast and should take regular medications, including any treatment for diabetes, with the exception of any prohibited concomitant medication. Subjects requiring insulin will self-administer their usualmorning insulin injection, taking into consideration their fasting status. Subjects will be instructed to bring in their insulin, as needed, to the clinic. Fasting blood glucose will be assessed before gastric emptying assessments to ensure a blood glucose of <275 mg / dL. Additional insulin may be given (titrated based on meal caloric content) to ensure a blood glucose of <275 mg / dL prior to the gastric emptying procedure. Likewise, low blood sugar (hypoglycemia; blood glucose of <60 mg / dL) showed be managed. o Subjects will be required to washout of the following agents within 14 days or 5 half-lives (whichever is longer) prior to beginning the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary Baseline Period until the end of the study:■ Metoclopramide;■ Domperidone;■ Erythromycin;■ Pyridostigmine;■ Chronic opiates (a subject will be allowed <72-hour use of opioids once during the Treatment Period, if required);■ Daily use of marijuana and / or tetrahydrocannabinol (Subjects who test positive for tetrahydrocannabinol at Visit 1 may be eligible to continue in the study provided that they have a prescription for this substance, have been on a stable dose for at least 6 months prior to Screening, and agree to avoid daily use of tetrahydrocannabinol during participation in the study. Subjects who do not have documented delayed gastric emptying within 2 years prior to Visit 1 and are required to complete a gastric emptying breath test must agree to abstain from prescribed marijuana and / or tetrahydrocannabinol for 2 weeks prior to this test);■ Anticholinergics; and■ Antiemetics (except for Protocol-specified rescue antiemetic medication).• Double-Blind Treatment Period of 12 weeks (Visit 3 to Visit 7, Days 1 to 84): o Adherence to the ANMS GCSLDD will be assessed at the time of randomization (Day 1) and must be >75% to be eligible for the study, or Sponsor approval;o Study drug will be administered (deudomperidone and / or placebo capsules) for 84 (±4) days and safety assessments will be performed; ANMS GCSI- DD questionnaire will be completed daily in the evening at approximately the same time each day; o The PAGI-QoL and the GERDQ will be completed at the clinic site at Visit 1, Visit 3 prior to the first dose of study drug, and at Visits 4, 5, 6. and 7; o All subj ects participating in the study will have trough PK samples collected at Visits 5 and 7 within 60 minutes prior to study drug administration. Subjects may opt to participate in a PK sub-set in which post-dose PK sample(s) will also be collected at Visit 5. These subjects will remain in the clinic for up to approximately 3 hours after the morning dose of study drug. In addition to the blood sample collected for PK within 60 minutes prior to study drug administration, blood samples will be collected from subjects in the PK sub-set at approximately 1 and 2 hours post-dose. If the subject is willing and able to remain in the clinic longer, a PK sample will also be collected at approximately 3 hours post-dose. Additional samples may be collected within the following post-dose windows on that same day if the subject is willing to return to the site: 4 to 8 hours and / or 8 to 12 hours. Subjects will be instructed to record the date and time of each dose on the 2 days prior to Visit 5 and also will be instructed not to take the study drug at home the day of Visit 5. Post-dose PK samples will be collected within ±15 minutes of the nominal time. o Safety will be evaluated through assessments of AEs. vital signs, physical examinations, clinical laboratory evaluations (chemistry, hematology, coagulation, urinalysis, and prolactin), and 12-lead ECG findings; and o Additionally, a single, optional PGx blood sample may be collected at any time during the Treatment Period.• Follow-Up Period: (Visit 8, Day 91 [±3 days]): o Subjects will have a follow-up visit approximately 1 week (±3 days) after the final dose of study drug to assess AEs, changes to concomitant medications (including use of rescue medications), vital signs, 12-lead ECG, prolactin, chemistry’, hematology, and coagulation. e of Procedures

[0056] Unscheduled Visits and / or additional follow-up may be required. For example, subjects with clinically significant abnormal laboratory findings, unresolved TEAEs, SAEs that require follow-up laboratories and review, or clinically significant AEs may necessitate further assessments.

[0057] B. Selection and Withdrawal of Subjects

[0058] Screening procedures, including vital sign assessments, may be repeated no more than 2 times for eligibility purposes. Subjects who are screened but failed to meet inclusion / exclusion criteria (despite potentially having undergone repeated screening assessments, if relevant) may be considered for re-screening.

[0059] (i) Inclusion Criteria

[0060] Subjects who meet all of the following criteria based on Screening assessments will be eligible to participate in the study:1. Is a male or female >18 years of age;2. Has a diagnosis of Type 1 or Type 2 diabetes, according to the American Diabetes Association criteria;3. Has a current diagnosis of diabetic gastroparesis defined by the following: a. Gastrointestinal symptoms felt to be consistent with gastroparesis (<?.g., postprandial nausea / vomiting, postprandial fullness, early satiety, bloating, and / or epigastric / abdominal pain) within 6 months prior to Screening; AND b. Documented delayed gastric emptying symptoms within the past 2 years as determined by GEBT, scintigraphy, wireless motility capsule, or manometry. Subjects who present with symptoms noted in Inclusion Criterion 3a but do not have documented delayed gastric emptying within the past 2 years of Visit 1 may complete a GEBT using13C-spirulina platensis during the Lead-In Period (between Days -21 to -12, inclusive). The GEBT U must be >110 minutes to be eligible to participate. Subjects with a GEBT ty <110 minutes may be considered for the study;4. Has a BMI between 18 and 45 kg / m2, inclusive, at Screening;5. Has an HbAlc level <10% at Screening and has stable, well -controlled blood glucose;6. Male subjects with female partners of childbearing potential must agree to use 2 medically accepted, highly effective methods of birth control from Day 1 through 90 days following the final dose of study drug. Medically accepted,highly effective methods of birth control for male subjects with female partners of childbearing potential include the following: latex condom with spermicide, diaphragm with intravaginal spermicide, cervical cap with spermicide, indwelling intrauterine device (hormonal or nonhormonal), implanted contraceptives, and oral contraceptives;7. Male subjects must agree to abstain from sperm donation from Day 1 through 90 days following the final dose of study drug;8. Female subjects with male partners must be surgically sterile (hysterectomy and / or bilateral oophorectomy), postmenopausal for at least 1 year (with confirmed follicle-stimulating hormone in postmenopausal range at the Screening Visit), or agree to use 1 medically accepted, highly effective method of birth control from Day -14 until 30 days following the final dose of study drug. Medically accepted, highly effective methods of birth control for female subjects with male partners include the following: latex condom with spermicide, diaphragm with intravaginal spermicide, cervical cap with spermicide, indwelling intrauterine device (hormonal or nonhormonal). implanted contraceptives, and oral contraceptives;9. Is willing to refrain from long-acting GLP-1 agonists, SGLT-2 inhibitors, or pramlintide from Screening through the end of treatment. Subjects who are taking GLP-1 agonists or SGLT-2 inhibitors may be considered for the study if they are willing to discontinue the medications for 3 days prior to beginning the ANMS GCSI-DD Baseline Period and agree to remain off of the medications throughout the study Treatment Period; and10. Is able to understand and willing to comply with all study visits, procedures, restrictions, discontinuation of medications, including those to treat gastroparesis.

[0061] (ii) Exclusion Criteria

[0062] Subjects who meet any of the following criteria will be excluded from participation in the study:1. Has a known cause of gastroparesis other than diabetes (e.g, idiopathic gastroparesis and / or gastroparesis attributed to surgery , viral illness, cancer, scleroderma, or other neurologic disorder);1. Has been hospitalized within the past year prior to Visit 1 for diabetic gastroparesis and / or diabetic ketoacidosis;Has a history of, or current, clinically significant arrhythmias, including ventricular tachycardia, ventricular fibrillation, and Torsades de pointes; Has evidence (based on Screening or baseline assessments) or history of clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies); surgical conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and cancer that resolved or has been in remission for >5 years prior to the Screening Visit); or any condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of the study drug. Cholecystectomy and appendectomy are allowed if the procedure(s) occurred >6 months prior to Screening; Has a history of prolactin-releasing pituitary tumor (z. e. , prolactinoma); Has 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; Has had pyloric injection of botulinum toxin within 6 months of Screening and / or planned injection(s) during the course of the study; Has a history of pyloroplasty, pyloromyotomy, or gastric peroral endoscopic myotomy procedure; Has total bilirubin, alkaline phosphatase, AST, or ALT levels greater than 2 x ULN or has a Child-Pugh classification grade of B or C at Screening; Has a serum creatinine level greater than 1.5 x ULN or has an estimated glomerular filtration rate <30 mL / min / 1.73 m2using the Chronic Kidney Disease Epidemiology Collaboration equation at Screening; Has thyroid-stimulating hormone levels that are significantly abnormal at Screening; Has an inability to perform a GEBT or has a fasting glucose >275 mg / dL on the day of the GEBT. This criterion applies only to those subjects without documented delayed gastric emptying within 2 years prior to Screening and who would be required to complete the GEBT to confirm eligibility. If the subject’s fasting blood glucose level is >275 mg / dL, the GEBT will not be performed.The subject will be allowed to return to the site within the next 1 to 3 days to complete the test, or the subject may be excluded from the study, if the subject no longer meets the criteria for stable, well-controlled blood glucose; Has a known allergy to eggs or spirulina. This criterion applies only to those subjects without documented delayed gastric emptying within 2 years prior to Screening and who would be required to complete the GEBT to confirm eligibility; Uses an investigational, prescription, or over-the-counter medication as follows: a. Actively participating in an experimental therapy study; received experimental therapy with a small molecule within 30 days of randomization or 5 half-lives (whichever is longer); or received experimental therapy with a large molecule within 90 days of randomization or 5 half-lives (whichever is longer); b. For inhibitors and inducers of CYP3A4 (whether a medication, herbal supplement, dietary supplement, nutraceutical, or food):■ For subjects who opt to provide PK. samples beyond the trough samples at Visits 5 and 7: ALL inhibitors and / or inducers of CYP3A4 are exclusionary7within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study;■ For all other subjects: the use of STRONG inhibitors and / or inducers of CYP3A4 are exclusionary within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study. Weak and moderate inhibitors and inducers of CYP3A4 are permitted; and■ For all subjects, the use of grapefruit, grapefruit products, star fruit products, and Seville oranges is prohibited from 48 hours prior to randomization until the end of treatment. c. Use of motility agents (including but not limited to metoclopramide, domperidone, erythromycin, pyridostigmine, etc ), other agents and medications that may affect gastric emptying (e.g.. all chronic opiates [a subject will be allowed <72-hour use of opioids once during the Treatment Period, if required], daily use of marijuana and / or tetrahydrocannabinol products [must be prescribed by a health care professional and the dose must be stable for >6 months for non-daily usage], and all anticholinergics), andantiemetics (except for Protocol-specified rescue antiemetic medication) within 14 days or 5 half-lives (whichever is longer) prior to beginning the ANMS GCSI-DD Baseline Period until the end of the study. For subjects who are required to complete a GEBT for eligibility, these agents must be discontinued at least 14 days or 5 half-lives (whichever is longer) prior to the GEBT; and d. Use of antipsychotics, antidepressants, anxiolytics, or prescription sleeping medications, with the exception of a stable dose for >6 months prior to Screening. Has a positive drug or alcohol test result at Screening without medical explanation, or a history of alcoholism or drug abuse within 2 years prior to Screening as defined by the Diagnostic and Statistical Manual of Mental Disorders 4th Edition, and / or ty pically consumes >14 alcoholic drinks weekly. One drink of alcohol is equivalent to Vi pint of beer (285 mL). 1 glass of spirits (25 mL), or 1 glass of wine (125 mL). A confirmatory drug or alcohol test may be performed with a different methodology if a false positive is suspected. Subjects who test positive for tetrahydrocannabinol at Visit 1 may be eligible to continue in the study provided that they have a prescription for this substance, have been on a stable dose for at least 6 months prior to Screening, and agree to avoid daily use of tetrahydrocannabinol during participation in the study. Subjects who do not have documented delayed gastric emptying within 2 years prior to Visit 1 and are required to complete a GEBT must agree to abstain from prescribed marijuana and / or tetrahydrocannabinol for 2 weeks prior to this test; Has evidence of ongoing illicit drug use; Has a known history' of or an ongoing eating disorder within 2 years of the Screening Visit; Is positive for human immunodeficiency virus antibody, hepatitis C virus antibody by RNA, or hepatitis B surface antigen at the Screening Visit; Is currently undergoing treatment with weight loss medication or prior weight loss surgery' (e.g, gastric bypass surgery ); Is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the course of the study; Is unable to swallow medication;21. Is currently receiving parenteral feeding or presence of a nasogastric or other enteral tube (e.g. PEG or PEJ tube) for feeding or decompression;22. Has a known or suspected gastric outlet obstruction e.g., peptic stricture) or other gastrointestinal mechanical obstruction as documented by upper gastrointestinal tract endoscopy or upper gastrointestinal radiographic series in the past 2 years;23. Has a known history or current diagnosis of intestinal malabsorption or pancreatic exocrine disease;24. Has ahistory of gastric surgery7such as fundoplication, gastrectomy, vagotomy, pyloroplasty, or bariatric procedure. Subjects who have a gastric pacemaker in place may be considered for the study if the pacemaker can be turned off for >14 days prior to beginning the ANMS GCSI-DD Baseline Period and throughout the remainder of the study. A history' of diagnostic endoscopy is not exclusionary;25. Has a history or presence of any medical condition or psychiatric disease, which could interfere with the conduct of the study or would put the subject at unacceptable risk;26. Has had prior exposure to deudomperidone;27. Has demonstrated prior lack of response to domperidone or known hypersensitivity' or intolerance to domperidone or any of the excipients in the deudomperidone formulation; or28. Is judged to be unsuitable for any other reason that may either place the subject at increased risk during participation or interfere with the interpretation of the study outcomes.

[0063] (iii) Randomization Criteria

[0064] Subjects who meet the following criteria will be randomized at Visit 3 (Day):1. Continues to satisty’ all inclusion / exclusion criteria;2. Has been off motility agents (including but not limited to metoclopramide, domperidone, ery thromycin, pyridostigmine, etc.), other agents and medications that may affect gastric emptying (e.g., all chronic opiates [a subject will be allowed <72-hour use of opioids once during the Treatment Period, if required], daily use of marijuana and / or tetrahydrocannabinol products [mustbe prescribed by a health care professional and the dose must be stable for >6 months for non-daily usage], and all anticholinergics), and anti emetics (except for Protocol-specified rescue anti emetic medication) within 14 days or 5 half-lives (whichever is longer) prior to beginning the ANMS GCSI-DD Baseline Period and is willing to remain off such medications until the end of the study;3. Demonstrates a confirmed diagnosis of diabetic gastroparesis as defined by the following: a. Gastrointestinal symptoms felt to be consistent with gastroparesis (e.g., postprandial nausea / vomiting, postprandial fullness, early satiety, bloating, and / or epigastric / abdominal pain) within 6 months prior to Screening; AND b. Documented delayed gastric emptying symptoms within the past 2 years as determined by GEBT, scintigraphy, wireless motility capsule, or manometry. Subjects who present with symptoms noted in Inclusion Criterion 3a but do not have documented delayed gastric emptying within the past 2 years of Visit 1 may complete a GEBT using13C-spirulina platensis during the Lead-In Period (between Days -21 to -12, inclusive). The GEBT ty must be >110 minutes to be eligible to participate. Subjects with a GEBT tv <110 minutes may be considered for the study;4. Meets one of the following criteria, EITHER “a” OR “b”: a. Has an ANMS GCSI-DD score that satisfies the following during the 14 days prior to randomization during which the subject has not been taking motility agents or antiemetics (with the exception of Protocol-specified rescue mediation):■ An average weekly Nausea Sub-Scale Score of >2 ("moderate" or greater);■ No day in which the Nausea Sub-Scale Score is 0; AND■ At least 2 episodes of vomiting each week. b. Has at least 7 days of diary entries AND the subject meets the following ANMS GCSI-DD scores AND has received the maximum amount of permitted rescue medication (z.e., a single dose of promethazine 25 mg. ondansetron 4 mg, or over-the-counter ginger product per day for 3 days per week):■ A Nausea Sub-Scale Score of >3 (‘‘severe’') on at least 4 of 7 days;■ No day in which the Nausea Sub-Scale Score is 0; AND■ At least 2 episodes of vomiting during the week.Vomiting (emesis) is clinically defined as the oral eviction of gastrointestinal contents, due to contractions of the gut and muscles of the thoracoabdominal wall, whereas regurgitation has been defined as egression of gastric contents to the mouth effortlessly. Subjects should be informed of the differences in vomiting versus regurgitation, defined as an act of bringing swallowed food back up into the mouth, and to document vomiting episodes accordingly.5. Adheres with the ANMS GCSI-DD during the Baseline Period, defined as adherence >75%, or Sponsor approval.

[0065] C. Study Objectives

[0066] (i) Primary Obj ective

[0067] The primary objective of this study is to assess the ability of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline in adult subjects with diabetic gastroparesis, based on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 2 w eeks of the 12-week Treatment Period, compared to placebo.

[0068] (ii) Secondary' Objectives

[0069] The secondary objectives of this study are to assess the effect of deudomperidone relative to placebo on the following parameters in adult subjects with diabetic gastroparesis:• The relationship between ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores and PGIS and PGIC over the 12-w eek Treatment Period;• The percentage of subjects with a history of a lack of response or who could not tolerate metoclopramide therapy or other prokinetics such as erythromycin, neostigmine, or bethanechol, who demonstrate clinical improvement of symptoms of gastroparesis. based on a composite of the average ANMS GCSI- DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 2 w eeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12- week Treatment Period;• The percentage of responders who demonstrate an average >0.5 reduction from baseline on the ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12- week Treatment Period;• The percentage of symptom-free days in the ANMS GCSI-DD Total and SubScale Scores over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline in adult subjects with diabetic gastroparesis, based on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 6 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the ANMS GCSI-DD Total and Sub-Scale Scores over the last 6 weeks of the 12- week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Total and Sub-Scale Scores over the last 6 weeks of the 12- week Treatment Period;• The percentage of symptom-free days in the ANMS GCSI-DD Total and SubScale Scores over the last 6 weeks of the 12-week Treatment Period;• The change from baseline in PGIS; and• The change from baseline in PGIC.

[0070] (iii) Exploratory Objectives

[0071] The exploratory' objectives of this study include assessment of the following in adult subjects with diabetic gastroparesis:• The change from baseline in the PAGI-QoL Instrument Survey;• The change from baseline in the GERDQ;• The change from baseline to Week 12 in subjects’ HbAlc, insulin requirements, and diabetic medications;• Characterization of the absorption of deudomperidone and concentrations of its primary metabolites at steady state; and• Characterization of the exposure-response relationships of deudomperidone and various measures of efficacy and / or safety7may also be undertaken.

[0072] (iv) Safety Objective

[0073] The safety objective includes assessment of the safety of deudomperidone compared to placebo in adult subjects with diabetic gastroparesis.

[0074] D. Study Treatments

[0075] (i) Treatment Groups

[0076] This study is planned to include 3 treatment groups with 133 subjects in each group. Subjects who complete the Screening and Lead-In Periods and remain eligible will be randomized in parallel to 1 of 3 treatment groups in a 1 : 1 : 1 fashion for 12 weeks:• Deudomperidone 15 mg BID, administered as a single 10-mg capsule and a single 5-mg capsule;• Deudomperidone 10 mg BID, administered as a single 10-mg capsule of deudomperidone and a single placebo capsule; or• Placebo for deudomperidone BID, administered as 2 matching placebo capsules.

[0077] (ii) Randomization and Blinding

[0078] This is a randomized, double-blind study. Randomization of subjects will be managed by an IRT system. Subjects who complete the Screening and Lead-In Periods, and remain eligible will be randomized in parallel to 1 of 3 treatment groups in a 1 : 1 : 1 fashion for 12 weeks. Randomization will occur at Visit 3 (Day 1). Subjects will be stratified according to their gender at birth (female, male) and by the baseline composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores (<2.6 versus >2.6).

[0079] Blinding will be maintained by administration of 2 dosage units for each dose. As such, subjects randomized to the 10 mg dose level will receive a single 10-mg capsule and a single placebo capsule for each dose. Subjects randomized to the 15 mg dose level will receive a single 10-mg capsule and a single 5-mg capsule for each dose. Finally, subjects randomized to placebo will receive 2 matching placebo capsules for each dose.

[0080] The study drug blind will be maintained through database lock. Randomized subjects who prematurely discontinue the study will not be replaced.

[0081] (iii) Drug Supplies

[0082] Deudomperidone drug product capsules consist of deudomperidone drug substance in a size 2C. oval-shaped, blue opaque, softgel capsule. Each deudomperidone softgel capsule will contain either 10 mg or 5 mg of active deudomperidone drug substance. The deudomperidone fdl formulation composition contains the inactive ingredients in Table 2.

[0083] A matching placebo softgel capsule, with a formulation containing the same inactive ingredients (without deudomperidone drug substance) will also be provided. See, Table 3.

[0084] The softgel capsules (capsule containing deudomperidone drug substance and the placebo capsule) will be packaged in blister packs to achieve the doses required for the study.

[0085] (iv) Study Drug Administration

[0086] All randomized subjects will take a dose of blinded study drug (deudomperidone and / or placebo capsules) orally with approximately 240 mL of w ater BID. An approximate 12-hour interval (e.g., 8:00 am to 8:00 pm) will be maintained between each dose for a given individual. Subjects will be required to fast 2 hours before and 1 hour after all doses. Subjects in the PK sub-set who will be providing a post-dose PK sample at Visit 5 will be required to fast for a minimum of 8 hours prior to the morning dose of study drug. Subjects will be provided study drug for self-administration for doses not administered at the site.

[0087] In the event that a subject misses their scheduled dose and becomes aware of the missed dose within 2 hours of their scheduled dosing time, the subject should be instructed to take their assigned dose of study drug at the time they realized that the dose was missed. If the subject should become aware of the missed dose more than 2 hours after their scheduled dosing time, the subj ect should be instructed to skip this dose of study drug and resume the assigned dose of study drug at the next scheduled time.

[0088] Prior and Concomitant Medications and / or Procedures

[0089] (v) Excluded Medications, Foods, and / or Procedures

[0090] Use of the following investigational, prescription, or over-the-counter medications is not permitted during the study:• Antipsychotics, antidepressants, anxiolytics, or prescription sleeping medications, with the exception of a stable dose for >6 months prior to Screening;• Pramlintide;• SGLT-2 inhibitors or GLP-1 agonists with long half-lives (e.g., Bydureon® [exenatide extended release], Victoza® [liraglutide], Tanzeum® [albiglutide], or Trulicity® [dulaglutide]);• Experimental therapy with a small molecule within 30 days of randomization or 5 half-lives (whichever is longer); or experimental therapy with a large molecule within 90 days of randomization or 5 half-lives (whichever is longer);• For inhibitors and inducers of CYP3A4 (whether a medication, herbal supplement, dietary7supplement, nutraceutical, or food): o For subjects who opt to provide PK samples beyond the trough samples at Visit 5 and 7: ALL inhibitors and / or inducers of CYP3A4 are exclusionary within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study; o For all other subjects: the use of STRONG inhibitors and / or inducers of CYP3A4 are exclusionary within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study. Weak and moderate inhibitors and inducers of CYP3A4 are permitted; and o For all subj ects, the use of grapefruit, grapefruit products, star fruit products, and Seville oranges is prohibited from 48 hours prior to randomization until the end of treatment.• Medication, herbal supplements, dietary' supplements, or nutraceuticals with potential to prolong QT within 28 days prior to the first dose of study drug until the end of the study;• Use of motility' agents (including but not limited to metoclopramide, domperidone, erythromycin, pyridostigmine, etc.), other agents and medications that may affect gastric emptying (e.g.. all chronic opiates [a subject will be allowed <72-hour use of opioids once during the Treatment Period, if required], daily use of marijuana and / or tetrahydrocannabinol products [must be prescribed by a health care professional and the dose must be stable for >6 months for non-daily usage], and all anticholinergics), and anti emetics (except for Protocol-specified rescue anti emetic medication) within 14 days or 5 half-lives (whichever is longer) prior to beginning the ANMS GCSI-DD Baseline Period until the end of the study. For subjects who are required to complete a GEBT for eligibility, these agents must be discontinued at least 14 days or 5 half-lives (whichever is longer) prior to the GEBT. Subjects who test positive for tetrahydrocannabinol at Visit 1 may be eligible to continue in the study provided that they have a prescription for this substance, have been on a stable dose for at least 6 months prior to Screening, and agree to avoid daily use of tetrahydrocannabinol during participation in the study. Subjects who do not have documented delayed gastric empty ing within 2 years prior to Visit 1 and are required to complete a GEBT must agree to abstain from prescribed marijuana and / or tetrahydrocannabinol for 2 weeks prior to this test;• Pyloric injection of botulinum toxin within 6 months of Screening and during the course of the study;• Weight loss medication or prior weight loss surgery (e.g., gastric bypass surgery); and• Parenteral feeding or presence of a nasogastric or other enteral tube (e.g., PEG or PEJ tube) for feeding or decompression.

[0091] Subjects who require further treatment with prohibited medications may be discontinued from study treatment and undergo follow-up study procedures.

[0092] (vi) Restricted Medications and / or Procedures

[0093] Subjects who experience severe symptoms of gastroparesis may receive promethazine (Phenergan®) 25 mg or ondansetron (Zofran®) 4 mg.

[0094] (vii) Allowed Medications and / or Procedures

[0095] Weak and moderate inhibitors and inducers of CYP3A4 are permitted for subjects not participating in the PK sub-set.

[0096] Subjects are allowed to continue on antipsychotics, antidepressants, anxiolytics, or prescription sleeping medications if they have been on a stable dose for >6 months prior to Screening.

[0097] A subject will be allowed <72-hour use of opioids once during the Treatment Period, if required.

[0098] Other medications that are not explicitly and previously excluded are permitted (e.g.. rescue medications) after approval.

[0099] (viii) Rescue Medications

[0100] Subjects who experience severe symptoms of gastroparesis during the study may receive promethazine (Phenergan) 25 mg or ondansetron (Zofran) 4 mg by mouth as described below.

[0101] Subjects should be encouraged to utilize over-the-counter ginger (e.g. , as capsules, soft chews, chewing gum, oil, or tea) at a maximum of 1000 mg once per day prior to using promethazine or ondansetron. Prior to taking any over-the-counter product(s), subjects should confirm that the specific products do not contain any Protocol-prohibited ingredients.

[0102] During the washout period (Days -35 to -22), subjects may receive rescue medication as needed.

[0103] However, during the 3-week Lead-In Period (Days -21 to -1), subjects who experience severe symptoms of gastroparesis may only receive a single dose of promethazine 25 mg, ondansetron 4 mg, or over-the-counter ginger product per day for 3 days per week. During the ANMS GCSI-DD Baseline Period, subjects should be strongly encouraged to avoid rescue medications, if possible, and if used, to do so sparingly.

[0104] If a subject’s symptoms of gastroparesis are so severe that is believed that they require more than the maximum allowed doses of rescue medication AND they have completed 7 days of diary entries AND they meet Randomization Criteria, including Randomization Criterion 4b, they may proceed directly to randomization.

[0105] After randomization, the use of rescue medication will be limited to 1 dose per day for up to 3 days per week only when subjects experience nausea and / or vomiting of CTCAE Grade 2 or greater. If the subject uses rescue medication once daily for 3 days perweek for 2 consecutive weeks, the subject will be discontinued from the study due to lack of efficacy. Subjects who require further treatment with prohibited medications may be discontinued from study treatment and undergo follow-up study procedures.

[0106] E. Efficacy Assessments

[0107] (i) Primary Efficacy Endpoint

[0108] The primary efficacy endpoint of this study is to assess the effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline in adult subjects with diabetic gastroparesis, based on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period, compared to placebo.

[0109] (ii) Secondary Efficacy Endpoints

[0110] The secondary efficacy endpoints of this study include the following assessments of the effect of deudomperidone relative to placebo in adult subjects with diabetic gastroparesis:• Estimates based on a composite of the average ANMS GCSI-DD Nausea SubScale and Vomiting Sub-Scale Scores using PGIS and PGIC as an anchor over the 12-week Treatment Period;• The percentage of subjects with a history of a lack of response or who could not tolerate metoclopramide therapy or other prokinetics such as erythromycin, neostigmine, or bethanechol, who demonstrate a >30% reduction from baseline on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects who are identified as responders, defined as an average >0.5 reduction from baseline on their ANMS GCSI-DD Nausea SubScale and Vomiting Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the average ANMS GCSI-DD Vomiting Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Nausea Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Vomiting Sub-Scale Score over the last 2 weeks of the 12- week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the average ANMS GCSI-DD Nausea Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Total Score over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the average ANMS GCSI-DD Total Score over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Early Satiety Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Postprandial Fullness Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Upper Abdominal Pain Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period;• The percentage of symptom-free days in the ANMS GCSI-DD Total Score, a composite of the Nausea and Vomiting Scores, Nausea Score, Vomiting Score, Early Satiety Score, Postprandial Fullness Score, and Upper Abdominal PainScore with each dose of deudomperidone over the last 2 weeks of the 12-week Treatment Period (symptomatic days are defined as scores assessed as >mild [ANMS GCSI-DD scores >2]);• All of the above endpoints assessed over the last 2 weeks of the 12-week Treatment Period will also be assessed over the last 6 weeks of the 12-week Treatment Period;• The change from baseline to Week 12 in the PGIS with each dose of deudomperidone; and• The change from baseline to Week 12 in the PG1C with each dose of deudomperidone.

[0111] (iii) Exploratory7Efficacy Endpoints

[0112] The exploratory efficacy endpoints of this study include assessment of the following in adult subjects with diabetic gastroparesis:• The effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms as compared to baseline gastroparesis, based on the average ANMS GCSI-DD Bloating Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period, compared to placebo;• The change from baseline with each dose of deudomperidone compared to placebo after 12 weeks of treatment in the PAGI-QoL;• The change from baseline with each dose of deudomperidone compared to placebo after 12 weeks of treatment in the GERDQ;• Characterization of the absorption of deudomperidone and concentrations of its primary metabolites at steady state; and• Characterization of exposure-response relationships of deudomperidone and various measures of efficacy and / or safety may also be undertaken.

[0113] (iv) ANMS GCSI-DD Questionnaire

[0114] The ANMS GCSI-DD questionnaire covers 5 core relevant symptoms of gastroparesis: nausea, early satiety, postprandial fullness, upper abdominal pain, and vomiting. Bloating is included as an exploratory symptom. Symptoms are rated on a severity numeric response scale from 0 (none) to 4 (very severe). Vomiting is captured on a frequency response scale and scored as follows: 0 for no episodes, 1 for 1 episode, 2 for 2 episodes, 3 for 3 episodes, and 4 for 4 or more episodes.

[0115] Subjects will be instructed to complete the ANMS GCSI-DD questionnaire daily beginning at Screening, for the ANMS GCSI-DD Baseline Period, on the day of randomization, and daily from Days 1 to 84 (±4 days). Materials will be dispensed at the Screening Visit. Adherence to the ANMS GCSI-DD will be assessed at the time of randomization (Day 1) and must be >75% to be eligible for the study, or Sponsor approval. Questionnaires should be completed daily in the evening at approximately the same time each day.

[0116] Subjects will be instructed to complete the questionnaires rating their severity and vomiting episode responses as the worst severity of the symptom over the previous 24 hours before any rescue medication.

[0117] The ANMS GCSI-DD total gastroparesis symptom daily score will be calculated by adding the scores on each of the 5 symptom items and then dividing by 5; thus, the maximum total symptom score could be 4 (5 symptoms X maximum score of 4 = 20; 20 divided by 5 = 4). Baseline for analysis of the ANMS GCSI-DD Total and Sub-Scale Scores will be based on the average weekly score for the 7 to 14 days prior to randomization. Both the ANMS GCSI-DD Total and Sub-Scale Scores will be analyzed to compare symptom scores between the treatment groups.

[0118] (v) PGIS and PGIC

[0119] The PGIS assessment will be performed once weekly beginning at Visit 1. At Visit 3, the PGIS will be performed prior to the first dose of study drug and will constitute baseline. The PGIS is a single-item measure completed by subjects at clinic visits to assess current global severity over the past 7 days. The PGIS is assessed using a 5-point numerical rating scale. The PGIC assessments will be performed at Visits 4, 5, 6, and 7. The PGIC is a single-item measure completed by subjects at clinic visits to assess the change in gastroparesis symptoms since starting the study drug. The PGIC is assessed using a 5-point numerical scale.

[0120] (vi) PAGI-QoL Instrument Survey

[0121] The PAGI-QoL will be completed at the clinic site at Visit 1, Visit 3 prior to the first dose of study drug, and at Visits 4, 5, 6, and 7. The PAQI-QoL consists of 30 questions that ask about how some of the gastrointestinal problems a subject may be experiencing have affected the subject's overall quality of life and well-being.

[0122] (vii) Gastroesophageal Reflux Disease Questionnaire

[0123] The GERDQ will be completed at the clinic site at Visit 1, Visit 3 prior to the first dose of study drug, and at Visits 4, 5, 6. and 7. The GERDQ is a subject's assessment of their symptoms over the previous week. The GERDQ score is a sum of the individual question scores, ranging from 0 to 18.

[0124] (viii) Pharmacokinetics

[0125] PK samples will be collected according to Tables 1A and IB. Plasma concentrations of deudomperidone and its primary metabolites will be measured and will be used to estimate the following parameters:• Steady state Cmax based on the samples collected post-dose at Visit 5 in the initial PK sub-set; and• Steady state trough concentrations based on the samples collected prior to dosing at Visits 5 and 7.

[0126] (ix) PGx Assessments

[0127] For subjects who participate in the optional PGx assessment, a blood sample w ill be collected at any time during the Treatment Period.

[0128] The PGx samples may be used for genetic research to explore the underlying causes of variability and / or differences in response in PK, PD, and / or safety data following administration of deudomperidone. Subjects will be given the option to participate in the PGx assessment during the consenting process for the study.

[0129] F. Safety' Assessments

[0130] The safety of deudomperidone will be assessed from the time of informed consent until the end of the Follow-Up Period. All safety endpoints will be summarized descriptively. The safety endpoints will include the following:• Incidence of clinically significant changes in laboratory parameters, physical examination findings, 12-lead ECG parameters, weight measurement, and vital sign measurements;• TEAEs;• Treatment-emergent SAEs;• TEAEs leading to premature discontinuation of study drug; and• Treatment-emergent marked laboratory abnormalities.

[0131] Example 2: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Deudomperidone in Adult Subjects With Diabetic Gastroparesis

[0132] Brief Summary': The goal of this clinical trial is to evaluate if the study drug deudomperidone can help reduce the symptoms associated with diabetic gastroparesis in adult patients.

[0133] The main questions it aims to answer are:• To evaluate the efficacy of deudomperidone on symptoms of gastroparesis when given to patients with diabetic gastroparesis compared to a placebo• To evaluate the safety and tolerability of deudomperidone when given to patients with diabetic gastroparesis compared to a placebo

[0134] Participants will go through the following schedule:• Screening period ( 1 -2 visits)• Lead-in period (1 visit) o Will complete daily diary' and other Patient Reported Outcomes (PROs) as described in the protocol to assess eligibility for continued study participation• 12-week treatment period (5 visits) o Study drug taken twice daily by mouth o Will complete daily diaries and other PROs as described in protocol o 1 week follow-up (1 visit)

[0135] Researchers will compare the effects of the following treatments:• Drug = deudomperidone Dose 1• Drug = deudomperidone Dose 2• Drug = Placebo

[0136] Study Design

[0137] Study Type: Interventional

[0138] Estimated Enrollment: 400 participants

[0139] Allocation: Randomized

[0140] Intervention Model: Parallel Assignment

[0141] Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

[0142] Primary Purpose: Treatment

[0143] Arms and Interventions

[0144] Outcome Measures

[0145] Primary Outcome Measure:1. Effect of deudomperidone to significantly decrease the severity of gastroparesis- related symptoms as compared to baseline based on the composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores [Time Frame: Over the last 2 weeks of the 12-week Treatment Period as compared to baseline]

[0146] Secondary Outcome Measures:1. Safety of deudomperidone [Time Frame: Duration of study participation]• Incidence of clinically significant changes, in the Investigator's opinion, in laboratory' parameters, physical examination findings, 12-lead ECG parameters, weight measurement, and vital sign measurements;• TEAEs;• Treatment-emergent SAEs;• TEAEs leading to premature discontinuation of study drug; and• Treatment-emergent marked laboratory' abnormalities.2. Estimates based on a composite of the average ANMS GCSI-DD Nausea Sub¬Scale and Vomiting Sub-Scale Scores using PGIS and PGIC as an anchor SubScale [Time Frame: Over the last 2 weeks for the 12-week Treatment Period]3. Percentage of subjects with a history of a lack of response or who could not tolerate metoclopramide therapy or other prokinetics, who demonstrate a >30% reduction on a composite score [Time Frame: Over the last 2 weeks of the 12- weekTreatment Period as compared to baseline]Composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores4. Percentage of subjects who are identified as responders, defined as an average>0.5 reduction from baseline on their ANMSGCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores [Time Frame: Over the last 2 weeks of the 12- weekTreatment Period]ercentage of subjects achieving a >30% reduction from baseline on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Sub-Scale Scores [Time Frame: Over the last 2 weeks of the 12-week Treatment Period]ercentage of subjects achieving a >30% reduction from baseline on the averageANMS GCSI-DD Vomiting Sub-Scale Score [Time Frame: Over the last 2 weeks of the 12-week Treatment Period] ffect of deudomperidone to significantly decrease the severity of gastroparesis- related symptoms as compared to baseline [Time Frame: Over the last 2 weeks of the 12-week Treatment Period as compared to baseline]Based on the average ANMS GCSI-DD Nausea Sub-Scale Score ffect of deudomperidone to significantly decrease the severity of gastroparesis- related symptoms as compared to baseline [Time Frame: Over the last 2 weeks of the 12-week Treatment Period as compared to baseline]Based on the average ANMS GCSI-DD Vomiting Sub-Scale Scoreercentage of subjects achieving a >30% reduction from baseline on the averageANMS GCSI-DD Nausea Sub-Scale Score [Time Frame: Over the last 2 weeks of the 12-week Treatment Period] Effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms [Time Frame: Over the last 2weeks of the 12- week Treatment Period as compared to baseline]Based on the average ANMS GCSI-DD Total Score Percentage of subjects achieving a >30% reduction on the average ANMS GCSI-DD Total Score [Time Frame: Over the last 2 weeks of the 12-week Treatment Period as compared to baseline] Effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms [Time Frame: Over the last 2weeks of the 12- week Treatment Period as compared to baseline]Based on the average ANMS GCSI-DD Early Satiety Sub-Scale Score Effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms [Time Frame: Over the last 2weeks of the 12- week Treatment Period as compared to baseline]Based on the average ANMS GCSI-DD Postprandial Fullness Sub-Scale Score14. Effect of deudomperidone to significantly decrease the severity of gastroparesis-related symptoms [Time Frame: Over the last 2weeks of the 12- week Treatment Period as compared to baseline]Based on the average ANMS GCSI-DD Upper Abdominal Pain Sub-Scale Score15. Percentage of symptom-free days in the ANMS GCSI-DD Total Score, a composite of the Nausea and Vomiting Scores, Nausea Score. Vomiting Score. Early Satiety Score, Postprandial Fullness Score, and Upper Abdominal Pain Score with each dose of deudomperidone [Time Frame: Over the last 2 weeks of the 12-week Treatment Period]Symptomatic days defined as >mild (ANMS GCSI-DD scores >2)16. All above endpoints [Time Frame: Over the last 6 weeks of the 12-week Treatment Period]17. Change in the PGIS with each dose of deudomperidone [Time Frame: From baseline to Week 12]18. Change in the PGIC with each dose of deudomperidone [Time Frame: From baseline to Week 12]

[0147] Eligibility Criteria

[0148] Key Inclusion Criteria:• Is a male or female >18 years of age:• Has a diagnosis of Type 1 or Type 2 diabetes, according to the American Diabetes Association criteria;• Has a current diagnosis of diabetic gastroparesis defined by the following: a. Gastrointestinal symptoms felt to be consistent with gastroparesis within6 months prior to Screening; AND b. Documented delayed gastric empty ing within the past 2 years or willing to complete a gastric emptying breath test.• Body mass index (BMI) between 18 and 45 kg / m2, inclusive;• Glycosylated hemoglobin (HbAlc) level <10% at Screening;• Willing to washout from ongoing treatment for gastroparesis.

[0149] Key Exclusion Criteria:• Has known cause of gastroparesis other than diabetes (e.g., idiopathic gastroparesis and / or gastroparesis attributed to surgery, viral illness, cancer, scleroderma, or other neurologic disorder);• History- or evidence of clinically significant arrhythmia;• History of pyloroplasty-, pyloromyotomy, or gastric peroral endoscopic myotomy, fundoplication, gastrectomy, vagotomy, or bariatric surgery;• Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube for feeding or decompression;• Pyloric injection of botulinum toxin within 6 months of Screening;• Positive test for drugs of abuse;• Females who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study.

[0150] Example 3

[0151] A. Study Objectives

[0152] (i) Primary Objective

[0153] The primary efficacy objective of this study- is to assess the ability of deudomperidone to significantly decrease gastroparesis-related symptoms as compared to baseline in adult subjects with diabetic gastroparesis, based on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12- week Treatment Period, compared to placebo.

[0154] (ii) Secondary^ Objectives

[0155] The secondary efficacy objectives of this study are to assess the effect of deudomperidone relative to placebo on the following parameters in adult subjects with diabetic gastroparesis:• The percentage of responders who demonstrate an average >0.5 reduction from baseline on the ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of symptom-free days in the ANMS GCSI-DD Total, a composite of the Nausea Sub-Scale and Vomiting Score, and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The relationship between ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores and Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) over the 12-week Treatment Period;• The percentage of subjects with a history of a lack of response or who could not tolerate metoclopramide therapy or other prokinetics such as erythromycin, neostigmine, or bethanechol, who demonstrate clinical improvement of symptoms of gastroparesis. based on a composite of the average ANMS GCSI- DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12- week Treatment Period;• The effect of deudomperidone to significantly decrease gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The change in the composite of the average ANMS GCSI-DD Nausea SubScale and Vomiting Scores from baseline to over the last 2 weeks of the 12- week Treatment Period among subjects receiving glucagon-like peptide-1 receptor agonist (GLP-1RA);• The percentage of responders among subjects receiving GLP-1RA who demonstrate an average >0.5 reduction from baseline on the ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects receiving GLP-1RA who achieve a >30% reduction from baseline on the ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The change in the ANMS GSCI-DD Total Score and a composite of gastroparesis-related symptoms from baseline to over the last 2 weeks of the 12- week Treatment Period among subjects receiving GLP-1RA;• All of the above primary7and secondary7objectives assessed over the last 2 weeks of the 12-week Treatment Period will also be assessed over the last 6 weeks of the 12-week Treatment Period;• The change from baseline in PGIS; and• The change from baseline in PGIC.

[0156] The secondary safety objective includes assessment of the safety of deudomperidone compared to placebo in adult subjects with diabetic gastroparesis.

[0157] (iii) Exploratory Objectives

[0158] The exploratory efficacy objectives of this study include assessment of deudomperidone relative to placebo on the following in adult subjects with diabetic gastroparesis:• The percentage of subjects who demonstrate an average >0.5 reduction from baseline on the ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period and over the last 6 weeks of the 12- week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12- week Treatment Period and over the last 6 weeks of the 12-week Treatment Period;• Estimates based on the average ANMS GCSI-DD Total and Sub-Scale Scores using PGIS and PGIC as an anchor over the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Bloating Sub-Scale Score;• The change from baseline in the Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QoL) Instrument Survey;• The change from baseline in the Gastroesophageal Reflux Disease Questionnaire (GERDQ);• The change from baseline to Week 12 in subjects’ hemoglobin Ale (HbAlc), insulin requirements, and diabetic medications;• The change from baseline to Week 12 in gastric emptying;• The effect on the percentage of days and number of days with any rescue medication usage;• The primary and secondary obj ectives which pertain to the evaluation of ANMS GCSI-DD vomiting scores will be subjected to exploratory analyses for vomiting severity;• Characterization of the absorption of deudomperidone and concentrations of its primary metabolites at steady state; and• Characterization of the exposure-response relationships of deudomperidone and various measures of efficacy and / or safety7may also be undertaken.

[0159] B. Study Description

[0160] (i) Summary of Study Design

[0161] This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of deudomperidone in adult subjects with diabetic gastroparesis after 12 weeks of treatment. See, FIG. 1.

[0162] The safety of deudomperidone will be assessed from the time of informed consent until the end of the Follow-Up Period. Subjects will be followed for efficacy and adherence to study' drug throughout the Double-Blind Treatment Period. Plasma concentrations of deudomperidone will also be measured at select visits during the DoubleBlind Treatment Period.

[0163] The total duration of study participation will be approximately 18 weeks including a Screening Period and Lead-In Period of <5 weeks, a Double-Blind Treatment Period of 12 weeks, and a Follow-Up Period of up to 1 week. Over the course of their participation, subjects will complete 8 visits.

[0164] Subjects who provide informed consent and complete the Screening and Lead-In Periods and remain eligible will be randomized in parallel to 1 of 3 treatment groups in a 1 : 1 : 1 fashion for 12 weeks:• deudomperidone 15 mg BID, administered as a single 10 mg capsule and a single 5 mg capsule;• deudomperidone 10 mg BID, administered as a single 10 mg capsule of deudomperidone and a single placebo capsule; or• Placebo for deudomperidone BID, administered as 2 matching placebo capsules.

[0165] Approximately 400 subjects (133 subjects per treatment group) will be randomized with 363 subjects anticipated to complete the 12-week Double-Blind Treatment Period. Subjects will be stratified according to their gender at birth (female, male) and by the baseline composite of the average ANMS GCSI-DD Nausea Sub-Scale and VomitingSeverity Scores (<2.6 vs >2.6).

[0166] Pharmacokineti cs

[0167] All subjects:• All subjects participating in the study will have trough PK samples collected at Visits 5 and 7. Trough samples should be collected within 60 minutes prior to study drug administration as applicable. Only subjects participating in PK Subset B will be required to dose at Visit 7.• Subj ects will be instructed to record the date and time of each dose on the 2 days prior to Visits 5 and 7 and will also be instructed not to take the study drug at home the day of these visits.• The exact date and time of the dose immediately prior to collection of each of these samples will be recorded and the exact date and time of each PK sample will be recorded.• In the event of a serious adverse event (SAE) or AE leading to withdrawal, an effort will be made to collect a PK sample as soon as possible. The date and time of the last dose of study drug prior to the PK sample and the date and time of the PK sample will be recorded.

[0168] PK Subset A:• Subj ects may opt to participate in PK Subset A in which post-dose PK sample(s) will be collected at Visit 5 only.• Subjects should present to this visit fasting for a minimum of 8 hours; however, a light meal may be consumed >2 hours prior and / or >3 hours after the morning dose of study drug if it is determined that food should be consumed by the subject (e.g, due to low blood glucose levels or symptoms of hypoglycemia) to ensure subject safety. The subject’s last meal time prior to dosing will also be recorded.• A blood sample for PK will be collected within 60 minutes prior to study drug administration.• Subjects will remain in the clinic for up to 3 hours after the morning dose of study drug and blood samples will be collected at approximately 1- and 2-hours post-dose. If the subject is willing and able to remain in the clinic longer, a PK sample will also be collected at approximately 3 hours post-dose.• Additional samples may be collected within the following post-dose windows on that same day if the subject is willing to remain at or return to the site: o 4 to 8 hours; and / oro 8 to 12 hours.• Subj ects will be instructed to record the date and time of each dose on the 2 days prior to these visits and will also be instructed not to take the study drug at home the day of these visits. Post-dose PK samples will be collected within ±15 minutes of the nominal time. The exact date and time of the dose of study drug and each PK sample on the day of the visit will also be recorded.• After approximately 30 subjects in PK Subset A complete Visit 5, emerging PK and safety data while blinded will be evaluated to individual subject assignment to determine the dose level(s) to be carried forward for the remainder of the study. Enrollment into PK subset A may continue following review. Subject may also opt to participate in PK subset B as described below.

[0169] PK Subset B:• Once the initial data review from PK Subset A is complete, a fresh subset of subjects may opt to participate in PK Subset B in which the subject will provide post-dose sample(s) to be collected at Visit 5, 6, and / or 7.• At Visit 5 and Visit 7, subjects should present to these visits fasting for a minimum of 8 hours, however, a light meal may be consumed >2 hours prior and / or >3 hours after the morning dose of study drug if it is determined that food should be consumed by the subject (<?.g., due to low blood glucose levels or symptoms of hypoglycemia) to ensure subject safety. On the day of Visit 6, the subject may take their study drug at home. The subject's last meal time prior to dosing will also be recorded for each of these visits.• Blood sample for PK will be collected within 60 minutes prior to study drug administration (Visit 5 and Visit 7 only) and 1 of the following post-dose windows at Visit 5, 6, or 7: o 1 to 4 hours; and / or o 4 to 8 hours; and / or o 8 to 12 hours.For subjects willing to provide a post-dose sample at more than one of the specified visits (Visits 5, 6. 7), the post-dose sample should be within a different window. For example, if the subject provides a post-dose sample within the 1- to 4-hour window at Visit 5, the subject should provide a sample within the 4- to 8-hour or 8- tol2- hour window at the subsequent visit (Visit 6 or Visit 7). If a subject opts to providepost-dose PK samples at all 3 visits and the Visit 6 sample is collected between 8 to 12 hours post-dose, then the Visit 7 sample should be collected between 4 to 8 hours post-dose.• For subjects who opt to provide more than 1 post-dose sample, efforts will be made to collect each sample within a different window. Subjects will be instructed to record the date and time of each dose on the 2 days prior to the visit and will also be instructed not to take the study drug at home the day of Visits 5 and / or 7. Post-dose PK samples will be collected within ±15 minutes of the nominal time. The exact date and time of the dose of study drug and each PK sample on the day of the visit will also be recorded.

[0170] Interim analysis

[0171] Following the PK Subset A evaluation, a blinded sample size re-estimation may occur. This analysis is to ensure the common standard deviation for the primary' efficacy endpoint has not deviated too much from the original assumption used in the sample size and power calculation. The study will not be stopped for efficacy or futility at the blinded analysis. As the analyses will be based on blinded data, the Type 1 error rate is strongly controlled and the final alpha will not need to be adjusted, as a result of this blinded data review.

[0172] During the study, 1 unblinded interim analysis (IA) will be performed once approximately 50% of the randomized subjects complete the End of Treatment (EOT) Visit or have discontinued early.

[0173] General study design and procedures

[0174] At the Screening Visit, all subjects will provide informed consent prior to any Protocol-specific procedures being performed. Subjects must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for study participation.

[0175] Except where noted for GEBT and subjects opting-in to the PK subset, overnight fasting is not required.

[0176] Subjects will be evaluated as follows:• Screening Period (Visit 1, Days -35 to -22): o Screening procedures will be performed, and subjects will begin washout of any applicable excluded medications. Subjects are required to washout of any prohibited medications for at least 14 days or 5 half-lives (whichever is longer) prior to beginning the ANMS GCSI-DD Baseline Period (defined asthe 14 days prior to randomization) and / or performing the GEBT at Visit 2; and o Beginning at the Screening Visit, subjects will record the ANMS GCSI-DD, PAGI-QoL, GERDQ, PGIS, and the use of allowable rescue medication.• Lead-In Period (Visit 2, Days -21 to -1):In addition to the clinic visit during this period, telephone visit(s) may be completed to assess adherence to the subject diaries, concomitant medications, and AEs. If the subject requires additional evaluation requiring an additional visit to the clinic, the subject may report to the clinic for additional procedures falling under Unscheduled Visits. o Subjects will be asked to continue completion of the ANMS GCSI-DD questionnaire daily and record the use of allowable rescue medication daily: o The average of the ANMS GCSI-DD daily measurements obtained over the 14 days prior to randomization will constitute “baseline” measurements; and o GEBT: A GEBT will be performed on a single day ideally between Days - 21 to -12 but may be performed outside of this window if there is sufficient time for GEBT analysis before randomization. The GEBT will be performed after a minimum of 14-day or 5 half-lives (whichever is longer) washout. Subj ects will fast for a minimum of 8 hours before the GEBT and for 4 hours following completion of the GEBT meal. Subjects who are actively using nicotine-containing products must refrain from using these products from the time of waking on the morning of the GEBT and until the test is complete. The GEBT will have breath samples obtained twice prior to consumption of a standardized,13C-enriched meal and then at 45, 90, 120, 150, 180, and 240 minutes after meal consumption. The meal should be consumed within 10 minutes. Fasting glucose will be assessed before GEBT to ensure a blood glucose level of <275 mg / dL. 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 Lead-In Period, the subject will be allowed to return to the site within the next 1 to 3 days to complete the test, or the subject may be excluded from the study, if the subject no longer meets the criteria for stable, well-controlled blood glucose. On the day of the GEBT, subjects will present at the clinic after an overnight fast and shouldtake regular medications, including any treatment for diabetes, with the exception of any prohibited concomitant medication. Subjects requiring insulin will self-administer their usual morning insulin injection, taking into consideration their fasting status. Subjects will be instructed to bring in their insulin, as needed, to the clinic. Fasting blood glucose will be assessed before gastric emptying assessments to ensure a blood glucose of <275 mg / dL. Additional insulin may be given (titrated based on meal caloric content) to ensure a blood glucose of <275 mg / dL prior to the gastric emptying procedure. Low blood sugar (hypoglycemia; blood glucose of <60 mg / dL) should be managed. It is preferred that the baseline GEBT be performed during the Lead-in Period (Visit 2, Day -21 to Day -12), however, the baseline GEBT may be performed outside of the noted Day - 21 to Day -12 window so long as the test is performed on a date that will allow adequate time for analysis of the GEBT prior to the anticipated randomization date. In the event that at Visit 1, the subject arrives to the clinic site and is not taking any excluded medications and meets all required criteria specified in the protocol (e.g., fasting for a minimum of 8 hours, glucose level <275 mg / dL, etc.), Visit 1 and Visit 2 procedures may be performed on the same day.• Double-Blind Treatment Period of 12 weeks (Visit 3 to Visit 7, Days 1 to 84): o Adherence to the ANMS GCSI-DD will be assessed at the time of randomization (Day 1) and must be >75% to be eligible for the study; o Study drug will be administered (deudomperidone and / or placebo capsules) for 84 (±4) days and safety assessments will be performed; o The use of allowable rescue medication will be recorded daily; o ANMS GCSI-DD questionnaire will be completed daily in the evening at approximately the same time each day; o The PAGLQoL and the GERDQ will be completed at the clinic site at Visit 3 prior to the first dose of study drug, and at Visits 4, 5, 6, and 7; and o All subj ects participating in the study will have trough PK samples collected at Visits 5 and 7. Trough samples should be collected within 60 minutes prior to study drug administration as applicable. Only subjects participating in PK Subset B will be required to dose at Visit 7. Subjects will be instructedto record the date and time of each dose on the 2 days prior to Visits 5 and 7 and will also be instructed not to take the study drug at home the day of these visits. The exact date and time of the dose immediately prior to collection of each of these samples will be recorded and the exact date and time of each PK sample will be recorded. o PK Subset A:Subjects may opt to participate in PK Subset A in which post-dose PK sample(s) will be collected at Visit 5 only. A blood sample for PK will be collected within 60 minutes prior to study drug administration. Subjects will remain in the clinic for up to 3 hours after the morning dose of study drug and blood samples will be collected at approximately 1- and 2- hours post-dose. If the subject is willing and able to remain in the clinic longer, a PK sample will also be collected at approximately 3 hours post-dose. Additional samples may be collected within the following post-dose windows on that same day if the subject is willing to remain at or return to the site: 4 to 8 hours; and / or 8 to 12 hours. Subjects will be instructed to record the date and time of each dose on the 2 days prior to these visits and will also be instructed not to take the study drug at home the day of these visits. Post-dose PK samples will be collected within ±15 minutes of the nominal time. The exact date and time of the dose of study drug and each PK sample on the day of the visit w ill also be recorded. Enrollment into PK subset A may continue. Subject may also opt to participate in PK subset B as described below. o PK Subset B:Once the initial data review from PK Subset A is complete, a fresh subset of subjects may opt to participate in PK Subset B in which the subject will provide additional post-dose sample(s) at Visits 5, 6, and / or 7 at one or more of the following post-dose windows: 1 to 4 hours, 4 to 8 hours, 8 to 12 hours. For subjects willing to provide a post-dose sample at more than one of the specified visits (Visits 5, 6, 7), the post-dose sample should be within a different window'. Subjects will be instructed to record the date and time of each dose on the 2 days prior to Visit 5, 6, and / or 7 and will be instructed not to take the study drug at home the day of Visits 5 and / or 7. Post-dose PK samples will be collected within ±15 minutes of the nominal time. The exact date and time of the dose of study drug and each PK sample on the day of the visit will also be recorded; o Subjects may opt to complete an additional GEBT to be performed at Visit 7 (EOT) / ET and will follow all requirements noted above for the GEBT during the Lead-In Period. If the subject’s fasting blood glucose level is >275 mg / dL despite the use of corrective insulin, the GEBT will not beperformed at this or any future visits and the remaining procedures will be performed to complete EOT; o Safety will be evaluated through assessments of AEs, vital signs, physical examinations, clinical laboratory evaluations (chemistry, hematology, coagulation, urinalysis, and prolactin), and 12-lead electrocardiogram (ECG) findings; and o Additionally, a single, optional pharmacogenomic (PGx) blood sample may be collected at any time during the Treatment Period.• Follow-Up Period: (Visit 8, Day 91 [±3 days]): o Subjects will have a follow-up visit approximately 1 week (±3 days) after the final dose of study drug to assess AEs. changes to concomitant medications (including use of rescue medications), vital signs, 12-lead ECG, prolactin, chemistry', hematology7, and coagulation.

[0177] Unscheduled Visits and / or additional follow-up may be required. For example, subjects with clinically significant abnormal laboratory findings, unresolved TEAEs, SAEs that require follow-up laboratories and review, or clinically significant AEs may necessitate further assessments.

[0178] C. Selection and Withdrawal of Subjects

[0179] (i) Inclusion Criteria

[0180] A subject who meets all of the following criteria based on Screening assessments will be eligible to participate in the study:1. Is a male or female >18 years of age;2. Has a diagnosis of Type 1 or Type 2 diabetes, according to the American Diabetes Association criteria;3. Has a current diagnosis of diabetic gastroparesis defined by the following: a. Persistent gastrointestinal symptoms, that are consistent with gastroparesis (e.g, postprandial nausea / vomiting. postprandial fullness, early satiety, bloating, and / or epigastnc / abdominal pain) within 6 months prior to Screening; AND b. Documented delayed gastric emptying as determined by GEBT, scintigraphy, or manometry. While attempts to obtain historical documentation of gastric emptying should be made, in the event that thisinformation is unavailable, the GEBT completed during the Lead-In Period may be used to satisfy this criterion. Has a body mass index (BMI) between 18 and 45 kg / m2, inclusive, at Screening; Has an HbAlc level <10% at Screening and has stable, well -controlled blood glucose; If receiving treatment with GLP-1RA, may be considered for the study if ALL of the following criteria are satisfied: a. Has been on a stable dose of GLP-1RA for a minimum of 3 months before Screening and is anticipated to sustain the same dose during GEBT and throughout the study; b. Is tolerating the GLP- IRA well; c. None of the study -qualifying signs / symptoms of gastroparesis (e.g., postprandial nausea / vomiting, postprandial fullness, early satiety, bloating, or epigastric / abdominal pain) are solely attributable to the use of GLP-1RA; AND d. The symptoms of gastroparesis preceded the initiation of GLP- IRA therapy. Male subjects with female partners of childbearing potential must agree to use 2 medically accepted, effective methods of birth control from Day 1 until 90 days following the final dose of study drug. Medically accepted, effective methods of birth control for male subjects with female partners of childbearing potential include the following: o Latex condom with spermicide; o Diaphragm with intravaginal spermicide; o Cervical cap with spermicide; o Indwelling intrauterine device (hormonal or nonhormonal); o Implanted contraceptives; o Oral contraceptives; and o Vasectomy (if performed at least 6 months before study drug administration). Male subjects must agree to abstain from sperm donation from Day 1 until 90 days following the final dose of study drug; Female subjects with male partners must be surgically sterile (hysterectomy and / or bilateral oophorectomy), postmenopausal (defined as a female >50 yearsof age with spontaneous amenorrhea for at least 1 year and a follicle-stimulating hormone in the postmenopausal range at the Screening Visit, based on the laboratory's ranges), or agree to use 2 medically accepted, effective methods of birth control from Day -14 until 60 days following the final dose of study drug. Medically accepted, effective methods of birth control for female subjects with male partners include the following: o Latex condom with spermicide; o Diaphragm with intravaginal spermicide; o Cervical cap with spermicide; o Indwelling intrauterine device (hormonal and nonhormonal); o Vasectomy in the male partner (if performed at least 6 months before study drug administration); and o Implanted or oral contraceptives.10. Is willing and able to refrain from pramlintide from Screening until EOT; and11. Can understand and comply with all study visits, procedures, restrictions, discontinuation of medications, including those to treat gastroparesis (as specified in the Protocol) and provide written informed consent according to institutional and regulatory' guidelines.

[0181] (ii) Exclusion Criteria

[0182] A subject who meets any of the following criteria will be excluded from participation in the study:1. Has a known primary' cause of gastroparesis other than diabetes (e.g. , idiopathic gastroparesis, gastroparesis attributed to surgery, viral illness, cancer, medications, scleroderma, or other neurologic disorder);2. Has been hospitalized within the past year prior to Visit 1 for diabetic gastroparesis and / or diabetic ketoacidosis;3. Has a history' of, or current, clinically significant arrhythmias, including ventricular tachycardia, ventricular fibrillation, and Torsades de Pointes;4. Has evidence (based on Screening or baseline assessments) or history of clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies); surgical conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and cancer that resolved or has been in remission for >5 years prior to the Screening Visit); orany condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of the study drug. Cholecystectomy and appendectomy are allowed if the procedure(s) occurred >6 months prior to Screening; Has a history of prolactin-releasing pituitary tumor (e.g. , prolactinoma); Has 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; Has had pyloric injection of botulinum toxin within 6 months of Screening and / or planned injection(s) during the study; Has a history of pyloroplasty, pyloromyotomy, or gastric peroral endoscopic myotomy procedure; Has total bilirubin, alkaline phosphatase, AST, or ALT levels >2 x ULN or has a Child-Pugh classification grade B or C at Screening; Has an estimated glomerular filtration rate <30 mL / min / 1.73 m2using the Chronic Kidney Disease Epidemiology Collaboration equation at Screening; Has thyroid-stimulating hormone levels that are abnormal at Screening; Has an inability to perform GEBT or has a fasting glucose >275 mg / dL on the day of the baseline GEBT (Visit 2). 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 Lead-In Period, the subject will be allowed to return to the site within the next 1 to 3 days to complete the baseline GEBT test, or the subject may be excluded from the study, if the subject no longer meets the criteria for stable, well-controlled blood glucose (Inclusion Criterion 5). Subjects who are actively using nicotine-containing products must refrain from using these products from the time of waking on the morning of the GEBT until the test is complete; Has a known allergy to eggs or spirulina; Uses an investigational, prescription, or over-the-counter medication as follows: a. Actively participating in an experimental therapy study; received experimental therapy with a small molecule within 30 days of randomization or 5 half-lives (whichever is longer); or receivedexperimental therapy with a large molecule within 90 days of randomization or 5 half-lives (whichever is longer); b. For inhibitors and inducers of CYP3A4 (whether a medication, herbal supplement, dietary' supplement, nutraceutical, or food):■ For subjects who opt to provide pharmacokinetic (PK) samples beyond the trough samples at Visits 5 and 7: ALL inhibitors and / or inducers of CYP3A4 are exclusionary within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study;■ For all other subjects: the use of STRONG inhibitors and / or inducers of CYP3A4 are exclusionary within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study. Weak and moderate inhibitors and inducers of CYP3A4 are permitted; and■ For all subjects, the use of grapefruit, grapefruit products, star fruit products, and Seville oranges is prohibited from 48 hours prior to randomization until EOT. c. Use of motility agents (including but not limited to metoclopramide, domperidone, erythromycin, pyridostigmine, etc ), other agents and medications that may affect gastric emptying (e.g, all anticholinergics), and antiemetics (except for Protocol-specified rescue antiemetic medications) within 7 days or 5 half-lives (whichever is longer) prior to the baseline GEBT (Visit 2) and / or beginning the ANMS GCSI-DD Baseline Period (defined as 14 days prior to randomization) and refrain use until the end of the study; d. Use of regularly scheduled opioids or anticipated use of scheduled opioids during the course of study participation. Up to a 72-hour course of prescribed non-extended release opioid medication is permitted during the Treatment Period of the study. If any subject is taking opioid medication prior to the GEBT, the opioid must be discontinued at least 72 hours or 5 half-lives (whichever is longer) before start of the GEBT. e. Daily use of marijuana and / or tetrahydrocannabinol (THC)-containing products. Subjects who do not use THC daily may be considered for the study if the use of the product is for medical reasons as noted in Exclusion Criterion 15;f. Use of variable doses of antidepressants, anxiolytics, antipsychotics or prescription sleeping medications during the 3 months prior to Screening; and g. Medications, herbal supplements, dietary supplements, or nutraceuticals that are known to prolong QT within 28 days prior to the first dose of studydrug until the end of the study. Has a positive drug or alcohol test result at Screening without medical explanation, or a history of alcoholism or drug abuse within 2 years prior to Screening as defined by the Diagnostic and Statistical Manual of Mental Disorders 4thEdition, and / or typically consumes >14 alcoholic drinks weekly. One drink of alcohol is equivalent to Vi pint of beer (285 mL), 1 glass of spirits (25 mL), or 1 glass of wine (125 mL). A confirmatory drug or alcohol test may be performed with a different methodology7if a false positive is suspected. Cotinine will be tested at Screening only. Subjects who test positive for THC at Visit 1 may be eligible to continue in the study provided that they have a prescription for this substance and agree to avoid daily use of THC-containing products during participation in the study. Subjects who are on a stable, nondaily regimen must agree to abstain from prescribed marijuana and / or THC- containing products for >24 hours prior to the GEBT. Frequency of use must be clearly understood by the site and documented in source. Cotinine is non- exclusionary and subjects who test positive for cotinine are eligible to continue in the study. Subjects who are actively using nicotine-containing products should remain on an approximately stable frequency of use during the study with the exception of the day of a GEBT on which the subject must refrain from using these products from the time of waking on the morning of the GEBT and until the test is complete; Has evidence of ongoing illicit, recreational drug use; Has a known history of or an ongoing eating disorder within 2 years of the Screening Visit; Is positive for human immunodeficiency virus antibody, hepatitis C virus antibody with confirmatory RNA, or hepatitis B surface antigen at the Screening Visit;Is currently undergoing treatment with weight loss medication or prior weight loss surgery (e.g. gastric bypass surgery); Is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study; Is unable to swallow medication; Is currently receiving parenteral feeding or presence of a nasogastric or other enteral tube (e.g.. percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jej unostomy [PEJ] tube) for feeding or decompression; Has a known or suspected gastric outlet obstruction (e.g, peptic stricture) or other gastrointestinal mechanical obstruction as documented by upper gastrointestinal tract endoscopy or upper gastrointestinal radiographic series in the past 2 years; Has a known history or current diagnosis of intestinal malabsorption or pancreatic exocrine disease; History of severe constipation and defined as the occurrence of 2 of the following criteria during the previous 3 months or more: <2 spontaneous (e.g, not induced by a laxative within 24 hours) bowel movements per w eek; >25% of stools were lumpy and / or hard; sensation of incomplete evacuation following >25% of stools; straining at defecation for >25% of the time; and / or dependence on (z.e., daily use of) osmotic or stimulant laxatives; Has ahistory of gastric surgery such as fundoplication. gastrectomy, vagotomy, pyloroplasty, or bariatric procedure. Subjects who have a gastric pacemaker in place may be considered for the study if the pacemaker can be turned off for >14 days prior to beginning the ANMS GCSI-DD Baseline Period and throughout the remainder of the study. A history of diagnostic endoscopy is not exclusionary; Has a history or presence of any medical condition or psychiatric disease, which could interfere with the conduct of the study or would put the subject at unacceptable risk; Has demonstrated prior lack of response to domperidone or known hypersensitivity or intolerance to domperidone or any of the excipients in the deudomperidone formulation; or29. Is unsuitable for any other reason that may either place the subject at increased risk during participation or interfere with the interpretation of the study outcomes.

[0183] (iii) Randomization Criteria

[0184] A subject who meets the following criteria will be randomized at Visit 3 (Day 1):1. Continues to satisfy all inclusion / exclusion criteria;2. Has been off motility agents (including but not limited to metoclopramide, domperidone, erythromycin, pyridostigmine, etc.), other agents and medications that may affect gastric emptying (e.g., all anticholinergics), and antiemetics (except for Protocol-specified rescue antiemetic medications) within 7 days or 5 half-lives (whichever is longer) prior to the baseline GEBT (Visit 2) and / or beginning the ANMS GCSI-DD Baseline Period (defined as 14 days prior to randomization) and refrain use until the end of the study. Subjects who meet criterion for GLP-1RA use (Inclusion Criterion 6) are not required to discontinue their GLP-1RA prior to the GEBT and should remain on their prescribed dose. Subjects who are actively using nicotine-containing products must refrain from using these products from the time of waking on the morning of the GEBT and until the test is complete. Subjects must agree to abstain use of opioids for >72 hours or 5 half-lives (whichever is greater) prior to GEBT. Subjects who are on a stable, non-daily regimen must agree to abstain from prescribed marijuana and / or THC -containing products for >24 hours prior to the GEBT;3. Demonstrates a confirmed diagnosis of diabetic gastroparesis as defined by the following: a. Persistent gastrointestinal symptoms, that are consistent with gastroparesis (e.g, postprandial nausea / vomiting. postprandial fullness, early satiety, bloating, and / or epigastnc / abdominal pain) within 6 months prior to Screening; AND b. Documented delayed gastric emptying symptoms as determined by 13C-Spirulina platensis GEBT during the Lead-In Period (ideally between Days -21 to -12 but may be performed outside of this window if there is sufficient time for GEBT analysis before randomization). The GEBT mustinclude kPCD values over a period of 240 minutes and should demonstrate a peak excretion occurring at 240 minutes (e.g., the maximum kPCD value occurs at 240 minutes) AND / OR kPCD values at 90, 120, OR 150 minute time points that are below the respective standard cutoff values.4. Has an ANMS GCSI-DD score that satisfies the following during the Baseline Period (i.e.. 14 days prior to randomization) during which the subject has not been taking motility agents or antiemetics (with the exception of Protocol- specified rescue medication): a. An average weekly Nausea Sub-Scale Score of >2 (“moderate” or greater); b. No day in which the Nausea Sub-Scale Score is 0 (“none”); AND c. A weekly average of >1 vomiting episode (of any severity). Vomiting (emesis) is clinically defined as the oral eviction of gastrointestinal contents, due to contractions of the gut and muscles of the thoracoabdominal wall, whereas regurgitation has been defined as egression of gastric contents to the mouth effortlessly. Subjects should be informed of the differences in vomiting vs regurgitation, defined as an act of bringing swallowed food back up into the mouth, and to document vomiting episodes accordingly.5. Adheres with the ANMS GCSI-DD during the Baseline Period, defined as adherence >75%.

[0185] D. Study Treatments

[0186] (i) Treatment Groups

[0187] This study is planned to include 3 treatment groups with 133 subjects in each group.

[0188] Subjects who provide informed consent and remain eligible after completion of the Screening and Lead-In Periods will be randomized in parallel to 1 of 3 treatment groups in a 1 : 1 : 1 fashion for 12 weeks:• deudomperidone 15 mg BID, administered as a single 10 mg capsule and a single 5 mg capsule;• deudomperidone 10 mg BID, administered as a single 10 mg capsule of deudomperidone and a single placebo capsule; or• Placebo for deudomperidone BID, administered as 2 matching placebo capsules.

[0189] (ii) Drug Supplies

[0190] (a) Formulation and Packaging

[0191] Deudomperidone drug product capsules consist of deudomperidone drug substance in a size 2C, oval-shaped, blue opaque, softgel capsule. Each deudomperidone softgel capsule will contain either 10 mg or 5 mg of active deudomperidone drug substance. The deudomperidone fdl formulation composition contains the inactive ingredients in Table 4.

[0192] A matching placebo softgel capsule, with a formulation containing the same inactive ingredients (without deudomperidone drug substance) will also be provided (Table 5).

[0193] The softgel capsules (capsule containing deudomperidone drug substance and the placebo capsule) will be packaged in blister packs to achieve the doses required for the study.

[0194] (b) Study Drug Administration

[0195] All randomized subjects will take a dose of blinded study drug (deudomperidone and / or placebo capsules) orally with approximately 240 mL of water BID. An approximate 12-hour interval (e.g., 8:00 am to 8:00 pm) will be maintained between each dose for a given individual. Subjects will be required to fast 2 hours before and 1 hour after all doses. Only subjects participating in PK Subset B will be required to dose at Visit 7. Subjects in the PK subsets who will be providing post-dose PK samples at Visits 5, 6, and / or 7 will be required to fast for a minimum of 8 hours prior to the morning dose of study drugand for >3 hours after study drug administration. However, a light meal may be consumed >2 hours prior and / or >3 hours after the morning dose of study drug if it is determined that food should be consumed by the subject (e.g., due to low blood glucose levels or symptoms of hypoglycemia) to ensure subject safety. Those subject who opt to complete a GEBT at Visit 7 will be required to fast for a minimum of 8 hours before the start of the GEBT meal, or if applicable, the morning dose of study drug and for 4 hours following the completion of the GEBT meal.

[0196] Subjects will be provided study drug for self-administration for doses not administered at the site.

[0197] If a subject misses their scheduled dose and becomes aware of the missed dose within 2 hours of their scheduled dosing time, the subject should be instructed to take their assigned dose of study drug at the time they realized that the dose was missed. If the subject should become aware of the missed dose more than 2 hours after their scheduled dosing time, the subject should be instructed to skip this dose of study drug and resume the assigned dose of study drug at the next scheduled time.

[0198] If the subject vomits after taking their scheduled dose of study drug, subjects will be instructed to note the time of study drug administration and time of vomiting and to resume their assigned dose of study drug at the next scheduled time. During the Treatment Period, subjects should attempt to note the time of vomiting in relation to time of study drug administration and report this to site staff during scheduled clinic visits. For subjects who opt-in to the PK subset, if the subject vomits within the first 4 hours after dosing and before post-dose PK sampling for that visit has been completed, PK sampling will cease. However, samples collected before vomiting will be analyzed.

[0199] Subjects in the PK subsets will be instructed to record the date and time of each dose on the 2 days prior to applicable Visits 5, 6, and / or 7 and will also be instructed not to take the study drug at home the day of Visits 5 and / or 7.

[0200] The exact date and time of the dose of study drug and each PK sample on the day of the visit will also be recorded.

[0201] (ii) Prior and Concomitant Medications and / or Procedures

[0202] (a) Excluded Medications, Foods, and / or Procedures

[0203] Use of the following investigational, prescription, or over-the-counter medications is not permitted during the study:• Pramlintide from Screening through EOT;• Variable dose of GLP-1RA;• Experimental therapy with a small molecule within 30 days of randomization or 5 half-lives (whichever is longer); or experimental therapy with a large molecule within 90 days of randomization or 5 half-lives (whichever is longer);• For inhibitors and inducers of CYP3A4 (whether a medication, herbal supplement, dietary supplement, nutraceutical, or food): o For subjects who opt to provide PK samples beyond the trough samples at Visit 5 and 7: ALL inhibitors and / or inducers of CYP3A4 are exclusionary within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study; o For all other subjects: the use of STRONG inhibitors and / or inducers of CYP3A4 are exclusionary7within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug until the end of the study. Weak and moderate inhibitors and inducers of CYP3A4 are permitted; and o For all subj ects, the use of grapefruit, grapefruit products, star fruit products, and Seville oranges is prohibited from 48 hours prior to randomization until EOT.• Medications, herbal supplements, dietary supplements, or nutraceuticals that are known to prolong QT within 28 days prior to the first dose of study drug until the end of the study;• Use of motility agents (including but not limited to metoclopramide, domperidone, erythromycin, pyridostigmine, etc.), other agents and medications that may affect gastric emptying (e.g., all anticholinergics), and antiemetics (except for Protocol-specified rescue anti emetic medication) within 7 days or 5 half-lives (whichever is longer) prior to the baseline GEBT (Visit 2) and / or beginning the ANMS GCSI-DD Baseline Period (defined as 14 days prior to randomization) and refrain use until the end of the study;• Use of regularly scheduled opioids or anticipated use of scheduled opioids during the course of study participation. Up to a 72-hour course of prescribed non-extended release opioid medication is permitted during the Treatment Period of the study. If any subject is taking opioid medication prior to the GEBT, the opioid must be discontinued at least 72 hours or 5 half-lives (whichever is longer) before start of the GEBT.• Daily use of marijuana and / or THC-containing products. Subjects who do not use THC daily may be considered for the study if the use of the product is for medical reasons. Subjects who test positive for THC at Visit 1 may be eligible to continue in the study provided that they have a prescription for this substance and agree to avoid daily use of THC-containing products during participation in the study. Subjects who are on a stable, non-daily regimen must agree to abstain from prescribed marijuana and / or THC-containing products for >24 hours prior to the GEBT. Frequency of use must be clearly understood by the site and documented in source. Cotinine is non-exclusionary and subjects who test positive for cotinine are eligible to continue in the study. Subjects who are actively using ni cotine-containing products should remain on an approximately stable frequency of use during the study with the exception of the day of a GEBT on which the subject must refrain from using these products from the time of waking on the morning of the GEBT and until the test is complete;• Variable doses of antidepressants, anxiolytics, antipsychotics, or prescription sleeping medications;• Pyloric injection of botulinum toxin within 6 months of Screening and / or planned injection(s) during the study;• Weight loss medication or prior weight loss surgery (e.g, gastric bypass surgery);• Parenteral feeding or presence of a nasogastric or other enteral tube (e.g., PEG or PEJ tube) for feeding or decompression;• Dependence on (z.e., daily use of) osmotic or stimulant laxatives;• Gastric pacemaker that cannot be turned off for >14 days prior to beginning the ANMS GCSI-DD Baseline Period and throughout the remainder of the study.

[0204] Subjects who require further treatment with prohibited medications may be discontinued from study treatment and undergo follow-up study procedures.

[0205] (b) Restricted Medications and / or Procedures

[0206] Subjects who experience severe symptoms of gastroparesis may receive promethazine (Phenergan®) 25 mg or ondansetron (Zofran®) 4 mg.

[0207] (c) Allowed Medications and / or Procedures

[0208] Weak and moderate inhibitors and inducers of CYP3A4 are permitted for subjects not participating in the PK subsets.

[0209] Eligible subjects are allowed to continue their stable dose of GLP-1RA.

[0210] Subjects are allowed to continue their antidepressants, anxiolytics, or prescription sleeping medications if they have been on a stable dose for >3 months prior to Screening.

[0211] A subject will be allowed a one-time only opioid use for severe pain (up to a 72-hour course of non-extended release formulation) during the Treatment Period, if required.

[0212] Other medications that are not explicitly and previously excluded are permitted (e.g., rescue medications).

[0213] Antacids, histamine-2 receptor antagonists, and proton pump inhibitors should only be taken ±2 hours from the time of study drug dosing. These medications may affect the oral bioavailability of deudomperidone.

[0214] (d) Rescue Medications

[0215] Subjects who experience severe symptoms of gastroparesis during the study may receive either promethazine (Phenergan) 25 mg or ondansetron (Zofran) 4 mg by mouth as described below, prescribed locally if needed.

[0216] Subjects should be encouraged to utilize over-the-counter ginger (e.g. , as capsules, soft chews, chewing gum, oil, or tea) at a maximum of 1000 mg once per day prior to using promethazine or ondansetron.

[0217] During the washout period (Days -35 to -22), subjects may receive rescue medication as needed.

[0218] However, during the 3-week Lead-In Period (Days -21 to -1), subjects who experience severe symptoms of gastroparesis may only receive a single dose of either promethazine 25 mg, ondansetron 4 mg. or over-the-counter ginger product per day for 3 days per week.

[0219] During the ANMS GCSI-DD Baseline Period, subjects should be strongly encouraged to avoid rescue medications, if possible, and if used, to do so sparingly. During the 14-day ANMS GCSIDD Baseline Period, if the subject uses rescue medications more than 3 days per week and / or exceeds the daily limit for the rescue medications as noted above, the subject may be discontinued from the study upon review.

[0220] After randomization, the use of rescue medication will be limited to 1 dose per day for up to 3 days per week only when subjects experience nausea and / or vomiting of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater. If thesubject uses rescue medication once daily for 3 days per week for 2 consecutive weeks, and is confirmed by site personnel, the subject will be discontinued from the study drug due to lack of efficacy but encouraged to remain in the study to continue remaining study procedures and assessments. These subjects will be asked to complete ET Visit and then proceed with the remaining study visits and procedures unless they withdraw consent. The use of rescue medication frequency will be recorded from Screening until EOT / ET, as a concomitant medication during the Follow-Up Period, and will be confirmed by the site personnel. Subjects who require further treatment with prohibited medications may be discontinued from study treatment and undergo follow-up study procedures.

[0221] Subjects should enter their daily ANMS GCSI-DD to describe the worst severity of each symptom during the past 24 hours. As such, the ANMS GCSI-DD questionnaire score should reflect the worst severity of each symptom score.

[0222] (e) General and Dietary Restrictions

[0223] Subjects should consistently maintain their usual diet and lifestyle during the study.

[0224] For all subjects, the use of grapefruit, grapefruit products, star fruit products, and Seville oranges is prohibited from 48 hours prior to randomization until EOT.

[0225] Subjects will be required to fast 2 hours before and 1 hour after all doses.

[0226] Subjects are required to fast for a minimum of 8 hours prior to the scheduled GEBTs and for 4 hours following completion of the GEBT meal.

[0227] Subjects in the PK subsets who will be providing post-dose PK samples at Visits 5, 6, and / or 7 will be required to fast for a minimum of 8 hours prior to the morning dose of study drug and for >3 hours after study drug administration.

[0228] E. Efficacy Assessments

[0229] (i) Efficacy Endpoints

[0230] (a) Primary Efficacy Endpoint

[0231] The primary efficacy endpoint of this study is to assess the effect of deudomperidone to significantly decrease gastroparesis-related symptoms as compared to baseline in adult subjects with diabetic gastroparesis, based on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12- week Treatment Period, compared to placebo.

[0232] (b) Secondary Efficacy Endpoints

[0233] The secondary efficacy endpoints of this study include the following assessments of the effect of deudomperidone relative to placebo in adult subjects with diabetic gastroparesis:• The percentage of subjects who are identified as responders, defined as an average >0.5 reduction from baseline on a composite of the average ANMS GCS1-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of symptom-free days in the ANMS GCSI-DD Total Score, a composite of the Nausea Sub-Scale and Vomiting Scores, and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period (symptomatic days are defined as scores assessed as >mild [ANMS GCSI-DD scores >2]);• Estimates based on a composite of the average ANMS GCSI-DD Nausea SubScale and Vomiting Scores using PGIS and PGIC as an anchor over the 12- week Treatment Period;• The percentage of subj ects with a history of a lack of response or who could not tolerate metoclopramide therapy or other prokinetics such as erythromycin, neostigmine, or bethanechol, who demonstrate a >30% reduction from baseline on a composite of the average ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period;• The change in the composite of the average ANMS GCSI-DD Nausea SubScale and Vomiting Scores from baseline to over the last 2 weeks of the 12- week Treatment Period among subjects receiving GLP-1RA;• The percentage of responders among subjects receiving GLP-1RA who demonstrate an average >0.5 reduction from baseline on the ANMS GCSI-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The percentage of subjects receiving GLP-1RA who achieve a >30% reduction from baseline on the ANMS GCS1-DD Nausea Sub-Scale and Vomiting Scores over the last 2 weeks of the 12-week Treatment Period;• The change in the ANMS GSCI-DD Total Score and a composite of gastroparesis-related symptoms from baseline to over the last 2 weeks of the 12- week Treatment Penod among subjects receiving GLP-1RA;• All of the above primary and secondary' endpoints assessed over the last 2 weeks of the 12-week Treatment Period w ill also be assessed over the last 6 weeks of the 12-week Treatment Period;• The change from baseline to Week 12 in the PGIS; and• The change from baseline to Week 12 in the PGIC.

[0234] (c) Exploratory Efficacy Endpoints

[0235] The exploratory efficacy endpoints of this study include assessment of deudomperidone relative to placebo on the following in adult subjects with diabetic gastroparesis:• The percentage of subjects who are identified as responders, defined as an average >0.5 reduction from baseline on the average ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period and over the last 6 weeks of the 12-week Treatment Period;• The percentage of subjects achieving a >30% reduction from baseline on the average ANMS GCSI-DD Total and Sub-Scale Scores over the last 2 weeks of the 12-week Treatment Period and over the last 6 weeks of the 12-week Treatment Period;• Estimates based on the average ANMS GCSI-DD Total and Sub-Scale Scores using PGIS and PGIC as an anchor over the 12-week Treatment Period;• The effect of deudomperidone to significantly decrease gastroparesis-related symptoms as compared to baseline, based on the average ANMS GCSI-DD Bloating Sub-Scale Score over the last 2 weeks of the 12-week Treatment Period and over the last 6 weeks of the 12-week Treatment Period;• The change from baseline compared to placebo after 12 weeks of treatment in the PAGI-QoL;• The change from baseline compared to placebo after 12 weeks of treatment in the GERDQ;• The change from baseline to W eek 12 in subj ects’ HbAl c, insulin requirements, and diabetic medications;• The change from baseline to Week 12 in gastric emptying as measured by GEBT;• The effect on the percentage of days and number of days with any rescue medication usage compared to placebo over 12 weeks of treatment;• The primary and secondary7endpoints which pertain to the evaluation of ANMS GCSI-DD vomiting scores will be subjected to exploratory7analyses for vomiting severity;• Characterization of the absorption of deudomperidone and concentrations of its primary7metabolites at steady state; and• Characterization of exposure-response relationships of deudomperidone and various measures of efficacy and / or safety may also be undertaken.

[0236] (ii) ANMS GCSI-DD Questionnaire

[0237] The ANMS GCSI-DD questionnaire covers 5 core relevant symptoms of gastroparesis: nausea, early satiety, postprandial fullness, upper abdominal pain, and vomiting. Bloating is included as an exploratory symptom. Symptoms are rated on a severity numeric response scale from 0 (none) to 4 (very severe). Vomiting is captured on a frequency response scale and scored as follows: 0 for no episodes, 1 for 1 episode, 2 for 2 episodes, 3 for 3 episodes, and 4 for 4 or more episodes.

[0238] Subjects will be instructed to complete the ANMS GCSI-DD questionnaire daily beginning at Screening, for the ANMS GCSI-DD Baseline Period, on the day of randomization, and daily from Days 1 to 84 (±4 days). Materials will be dispensed at the Screening Visit. Adherence to the ANMS GCSI-DD will be assessed at the time of randomization (Day 1) and must be >75% to be eligible for the study.

[0239] Subjects will be instructed to complete the questionnaires by rating their severity and vomiting episode responses as the worst severity of the symptom over the previous 24 hours and providing the number of vomiting episodes.

[0240] The ANMS GCSI-DD total gastroparesis symptom daily score will be calculated by adding the scores on each of the 5 symptom items and then dividing by 5; thus, the maximum total symptom score could be 4 (5 symptoms X maximum score of 4 = 20; 20 divided by 5 = 4).

[0241] Baseline for analysis of the ANMS GCSI-DD Total and Sub-Scale Scores will be based on the average of the daily measurements over the 14 days prior to randomization. Both the ANMS GCSI-DD Total and Sub-Scale Scores will be analyzed to compare symptom scores betw een the treatment groups. At least 4 days of valid, non-missing responses in a 7-day period will be required in order to obtain an average w eekly score for a given sub-scale score.

[0242] The ANMS GCSI-DD questionnaire will be documented.

[0243] (iii) PGIS and PGIC

[0244] The PGIS assessment will be performed once w eekly beginning at Visit 1. At Visit 3, the PGIS will be performed prior to the first dose of study drug and will constitute baseline.

[0245] The PGIS is a single-item measure completed by subjects at clinic visits to assess current global severity over the past 7 days. The PGIS is assessed using a 5-point numerical rating scale. The PGIS will be documented.

[0246] The PGIC assessments will be performed at Visits 4, 5. 6, and 7.

[0247] The PGIC is a single-item measure completed by subjects at clinic visits to assess the change in gastroparesis symptoms since starting the study drug. The PGIC is assessed using a 5-point numerical scale. The PGIC will be documented.

[0248] (iv) PAGI-QoL Instrument Survey

[0249] The PAGI-QoL will be completed at the clinic site at Visit 1. Visit 3 prior to the first dose of study drug, and at Visits 4, 5, 6, and 7.

[0250] The PAQI-QoL consists of 30 questions that ask about how some of the gastrointestinal problems a subject may be experiencing have affected the subject’s overall quality of life and well-being.

[0251] (v) Gastroesophageal Reflux Disease Questionnaire

[0252] The GERDQ will be completed at the clinic site at Visit 1, Visit 3 prior to the first dose of study drug, and at Visits 4, 5, 6, and 7.

[0253] The GERDQ is a subject’s assessment of their symptoms over the previous w eek. The GERDQ score is a sum of the individual question scores, ranging from 0 to 18.

[0254] (vi) Gastric Emptying Breath Test

[0255] The baseline measurement of gastric emptying by stable isotope GEBT will be completed at the clinic site. It is preferred that the baseline GEBT be performed during the Lead-in Period (Visit 2, Day -21 to Day -12), however, the baseline GEBT may be performed outside of the noted Day -21 to Day -12 w indow so long as the test is performed on a datethat will allow adequate time for analysis of the GEBT prior to the anticipated randomization date. In the event that at Visit 1, the subject arrives to the clinic site and is not taking any excluded medications and meets all required criteria specified in the protocol (e.g., fasting for a minimum of 8 hours, glucose level <275 mg / dL, etc.), Visit 1 and Visit 2 procedures may be performed on the same day.

[0256] If a subject is re-screened following a screen failure for a reason other than the results of the GEBT, the GEBT does not need to be repeated if the test was completed with the past 3 months prior to rescreening and the results met eligibility criteria.

[0257] For subjects who opt in, a GEBT will also be performed at Visit 7 (EOT) or ET.

[0258] Subjects who are actively using ni cotine-containing products must refrain from using these products from the time of waking on the morning of the GEBT and until the test is complete. Subjects must agree to abstain use of opioids for >72 hours or 5 half-lives (whichever is greater) prior to GEBT. Subjects who are on a stable, non-daily regimen must agree to abstain from prescribed marijuana and / or THC-containing products for >24 hours prior to the GEBT. Subjects are not required to discontinue their GLP-1RA prior to the GEBT and should remain on their prescribed dose.

[0259] The GEBT involves the collection of 2 pre-meal breath samples, ingestion of the GEBT meal, and collection of breath samples post-meal at 6 time points (45, 90. 120, 150, 180, and 240 minutes). The GEBT meal should be consumed within 10 minutes.

[0260] Eligibility will be determined by percent dose (abbreviated PCD) excreted at time t after consumption of the test meal:where:DOB = The measured difference in the ratio [13CO2 / 12CO2] between a post-meal breath specimen at any time (t-minutes) and the baseline breath specimen.CO2PR = CO2 Production Rate (mmol C02 / min) calculated using Schofield equations (26) which incorporate the subject’s age, gender, height, and weight.Rs = The ratio [i?CO2 / 12CO2] in the reference standard (Pee Dee belemnite) for these measurements, Rs= 0.011237213 = the atomic weight of Carbon- 1310 = A constant factor for converting unitsdose = the weight (mg) of Carbon-13 in the dose of [13C]-Spirulina platensis administered to the subject in the test meal. Since [13C] -S. platensis is approximately 43% Carbon-13, a dose of 100 mg [13C]-S. platensis corresponds to approximately 43 mg of Carbon-13.

[0261] Subjects whose kPCD values at either the 90, 120, or 150 minute time points are below the respective cutoff points and / or if the subject's maximum kPCD value occurs at 240 minutes will be qualified as having delayed gastric emptying.

[0262] Delayed cut-off parameters for each time point are as follows in Table 6.

[0263] To confirm the presence of delayed gastric emptying based on the established diagnostic criteria, all subjects will complete a baseline GEBT at Visit 2 as noted above. For subjects who opt in, a GEBT will be performed at Visit 7 (EOT)ZET.

[0264] (vii) Pharmacokinetic Assessments

[0265] PK samples will be collected according to the Schedule of Procedures in Table 7.

[0266] Plasma concentrations of deudomperidone and its primary metabolites will be measured and will be used to estimate the following parameters:• Steady state Cmax based on the samples collected post-dose at Visit 5 in the initial PK subset; and• Steady state trough concentrations based on the samples collected prior to dosing at Visits 5 and 7.

[0267] (viii) Pharmacogenomic Assessments

[0268] For subjects who provide written informed consent to participate in the optional PGx assessment, a blood sample will be collected at any time during the Treatment Period.

[0269] The PGx samples may be used for genetic research to explore the underlying causes of variability and / or differences in response in PK, PD, and / or safety data following administration of deudomperidone. Subjects will be given the option to participate in the PGx assessment during the consenting process for the study. The subject may withdrawconsent to participate in the PGx assessment at any time during the study without withdrawing consent to participate in the study.

[0270] F. Safety Assessments

[0271] The safety of deudomperidone will be assessed from the time of informed consent until the end of the Follow -Up Period. All safety7endpoints will be summarized descriptively. The safety endpoints will include the following:• Incidence of clinically significant changes in laboratory parameters, physical examination findings, 12-lead ECG parameters, w eight measurement, and vital sign measurements;• TEAEs;• Treatment-emergent SAEs;• TEAEs leading to premature discontinuation of study drug; and• Treatment-emergent marked laboratory abnormalities.

Claims

108039.000175What is claimed is:

1. A method of treating a human diagnosed with diabetic gastroparesis comprising administering a dosage form comprising 10 mg or 15 mg of deudomperidone BID, wherein the administration decreases the severity of the human’s gastroparesis-related symptoms, as compared to baseline.

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

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

4. The method of 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 hydroxy anisole, and (iv) 0.05 mg of butylated hydroxytoluene.

5. The method of 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 hydroxy anisole, and (iv) 0.05 mg of butylated hydroxy toluene.

6. The method of any one of claims 1-3 and 5, wherein the dosage form is a single capsule comprising 10 mg of deudomperidone.

7. The method of any one of claims 1-4, wherein the dosage form comprises a single capsule comprising 5 mg of deudomperidone and a single capsule comprising 10 mg of deudomperidone.

8. The method of any one of the preceding claims, wherein the patient has an average weekly nausea sub-scale score of 2 or greater, prior to the administration of deudomperidone.

9. The method of any one of the preceding claims, wherein the patient has a weekly average of at least one vomiting episode, prior to the administration of deudomperidone.108039.00017510. The method of any one of the preceding claims, wherein the decrease in severity is based on a composite of the human’s average ANMS GCSI-DD nausea sub-scale and vomiting sub-scale scores.

11. The method of claim 11, wherein the gastroparesis-related symptoms are one or more of postprandial nausea, postprandial vomiting, postprandial fullness, early satiety, bloating, epigastric pain, or abdominal pain.

12. The method of any one of the preceding claims, wherein the human’s ANMS GCSI- DD nausea sub-scale and vomiting scores reduce by at least 0.5 points, as compared to baseline.

13. The method of any one of the preceding claims, wherein the human’s ANMS GCSI- DD nausea sub-scale and vomiting scores reduce by at least 30%, as compared to baseline.

14. The method of any one of the preceding claims, wherein the human’s percentage of gastroparesis-related symptom-free days increases, as compared to baseline.

15. The method of any one of the preceding claims, wherein the human’s PAGI-QoL score improves, as compared to baseline.

16. The method of any one of the preceding claims, wherein the human’s GERDQ score improves, as compared to baseline.

17. The method of any one of the preceding claims, wherein the human’s PGIS score improves, as compared to baseline.

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